bluuebunny/crossref_metadata_2025 huggingface dataset:
Skilled forelimb use in the rat: amelioration of functional deficits resulting from neonatal damage to the frontal cortex by neonatal transplantation of fetal cortical tissue
Authors: Plumet Jocelyne , Cadusseau Josette , Roger Michel
Published: December 2019

Limb preference and dexterity of right and left forelimbs were studied in a food reaching task in normal rats (control group), in rats that sustained a neonatal lesion of the left frontal cortex (lesion group) and in animals that received a transplant obtained from the frontal cortex of 16-day-old embryos immediately after the lesion (graft group). In addition, an anatomical study of host–transplant interconnections was performed in several transplanted animals. The results indicate that the lesion slightly increased the preference for the limb ipsilateral to the lesion and transplantation of fetal cortical tissue did not restore the preference for the contralateral limb. Furthermore, lesion of the motor cortex induced a deficit in the dexterity of limb use in the food-reaching task. This motor deficit was more pronounced when the limb contralateral to the lesion was used. Transplantation of embryonic cortical tissue led to a reduction of the motor deficit. Compared to the lesion group, the graft group had a higher success rate and a lower percentage of motor abnormalities, whichever forelimb was used, ipsi- or contralateral to the transplant. Nevertheless, larger improvement was noted with contralateral forelimb usage. Functional recovery was not complete since the control group still performed significantly better than the graft group, although almost complete sparing in skilled reaching was noted when the limb ipsilateral to the transplant was used. Analysis of host–transplant interconnections indicates that the transplants sent fibers to the host spinal cord, caudate-putamen, thalamus and homotopic contralateral cortex and received projections from the host thalamus and contralateral cortex. It is therefore suggested that neonatal transplantation of fetal cortical tissue promotes functional recovery from damage to the motor cortex occurring at birth.
The pia mater — a conduit for regenerating axons after ventral root replantation
Authors: Risling M. , Carlstedt T. , Lindå H. , Cullheim S.
Published: December 2019

Previous studies have shown that replantation of avulsed ventral roots may lead to functional reinnervation of hindleg muscles. Regenerating motor axons may regrow for a considerable distance within the spinal cord before entering the replanted ventral root. In this study we show, in the rat and monkey, that many regenerating axons utilize an alternative pathway along the surface of the spinal cord, i.e. the pia mater. This type of reinnervation takes place entirely in the peripheral nervous system.
Morphological changes of retinal ganglion cells regenerating axons along peripheral nerve grafts: a Lucifer Yellow and silver staining study
Authors: Lau Kam Cheung , So Kwok-Fai , Cho Eric Yu Pang
Published: December 2019

The morphology of the retinal ganglion cells (RGCs) with their axons regenerating along a peripheral nerve graft at different post-grafting periods was studied by the intracellular injection of Lucifer yellow (LY) and silver staining methods. Several morphological features which were observed on developing RGCs, but not mature RGCs, have also been observed in the regenerating RGCs studied by the intracellular injection of LY. These morphological features observed on the regenerating RGCs included intraretinal axonal branches and collaterals, spine-like processes on the dendrites and soma, and short processes on the soma. These results suggest that damaged mammalian RGCs may be able to recapitulate certain cellular events which occur during normal development provided the regenerating cells are given the proper stimulus and a favorable environment for regrowth. From the results of both LY injection and silver staining experiments, it was found that the dendrites of the regenerating RGCs were, in general, much simpler than that of control Type I RGCs. However, regenerating RGCs with different degree of dendritic complexity could be observed in all post-grafting periods studied, and the dendritic complexity seems to decrease continuously with the increase in the post-grafting time. These results suggest that the ability to regenerate an axon is not closely related to dendritic responses and the peripheral nerve does not seem to be able to prevent the deterioration and retraction of the dendrites.
Reduction of lesion-induced deficits in visual reversal learning following cross-modal training
Authors: Clark Robert E. , Delay Eugene R.
Published: December 2019

Two experiments examined the effects of postoperative auditory intensity training on serial brightness reversal learning of visual decorticate rats. In Experiment 1 rats learned an avoidance response cued by a high intensity light prior to visual decortication. Six days later the rats were given either avoidance training with an auditory intensity cue, additional training with the preoperative visual cue, or no training. The next day all rats began a series of 8 brightness discrimination reversals. The no-training lesion group failed the early reversals but reached criterion in later reversals. Lesion rats retrained with visual cues failed early reversals with the low intensity light cue but not reversals with the high intensity cue. In contrast, lesion rats given auditory training easily reached criterion in all reversals. Experiment 2 followed a similar training sequence except auditory training was given after the second reversal. All rats showed rapid acquisition of all visual reversals subsequent to auditory training. These data suggest that generalization of a learning set by cross-modal transfer training with an intact modality can reduce reversal learning deficits following brain damage more efficiently than comparable training with the damaged system.
Effects of a Ginkgo biloba extract on two models of cortical hemiplegia in rats
Authors: Brailowsky S. , Montiel T. , Hernández-Echeagaray E. , Flores-Hernández J. , HernáNdez-Pineda R.
Published: December 2019

To screen drugs potentially useful in the pharmacological treatment of subjects with brain lesions, we studied the effects of chronic (7 and 30 days) treatments with a Ginkgo biloba extract (EGb761-IPSEN; EGb) in two animal models of cortical hemiplegia: one induced by motor cortex aspiration and another using a reversible inactivation of the motor cortex through chronic, localized infusion of y-aminobutyric acid (GABA), via osmotic minipumps. The elevated beam test was used in water-deprived animals trained to drink saccharin-sweetened solutions (with or without EGb) and to perform to criteria before the surgical procedures. From the day after surgery, the rats were administered 100 mg/kg of EGb daily for 7 or 30 days. In all groups with motor impairment in which the extract was administered, a faster and more complete recovery was observed, which was significantly different from that of rats which received only saccharin solutions. The salutary effect of EGb was more marked in ablation-induced hemiplegia than in the GABA-treated group. In the former injury model, EGb-treated animals had smaller ventricular diameters than non-treated rats. No differences concerning sensory deficits were detected among groups. EGb was also acutely administered during the epileptic syndrome that follows interruption of chronic GABA infusions (the GABA-withdrawal syndrome). No anticonvulsant effects of EGb were observed. These results suggest a potential use of EGb in brain-injured patients as this product shows little toxicity in animals and man after chronic administration. The active principles among terpenes (ginkgolides, bilobalides and flavonolheterosides present in the EGb) and the mechanisms for this beneficial effects remain to be elucidated.
Radial maze performance after hippocampal lesions: beneficial effects of nimodipine
Authors: Nelson Carl , Bawa Johny , Finger Stanley
Published: December 2019

Rats trained in an 8-arm radial maze were given electrolytic lesions of the dorsal hippocampus or sham operations. Within 24 h of surgery, approximately half of the rats in each groups began 14 daily oral treatments with the central calcium channel blocker, nimodipine. Retention testing began seven days after surgery. The untreated rats that received the larger hippocampal lesions did not relearn the maze within one month (2.5 times the preoperative mean number of days). The untreated rats that received the smaller lesions relearned within the allotted time but still showed clear deficits. Nimodipine improved the maze scores of the animals with the smaller lesions, but not those of the animals with the larger lesions. It was unclear whether nimodipine led to the sparing of more cells in the hippocampal region, or whether spared-but-affected cells were returning to normal modes of functioning more rapidly in the group with the smaller lesions. These findings suggest that spared hippocampus was mediating behavior, and extend previous findings from this laboratory showing that nimodipine can enhance recovery of function on higher cognitive tasks after hippocampal lesions.
Use of amphetamine in the treatment of aphasia
Authors: Walker-Batson Delaina , Unwin Hal , Curtis Sandra , Allen Elizabeth , Wood Midge , Smith Patricia , Devous Michael D. , Reynolds Sharon , Greenlee Ralph G.
Published: December 2019

The effects of d-amphetamine on the recovery of aphasia following stroke was examined in 6 patients. Patients entered the study between 10 and 30 days post onset and were followed for 3 months. The Porch Index of Communicative Ability was used to project a 6 month recovery score. By 3 months post onset, 5 of the 6 patients obtained scores in excess of 100% of the 6 month projections.
Interactive effects of insulin, IGF-I and GMl ganglioside on growth of PC12 cells
Authors: Yates Allan James , Conley John
Published: December 2019

PC12 cells grow in serum-free medium (SFM) if high doses of insulin (5–50 μg/ml), or combined insulin (5 μg/ml) and insulin-like growth factor-I (3 ng/ml) are added daily. Ganglioside GMl counteracts these effects in a dose-responsive fashion between 10 nM and 50 μM. This provides a serum-free system to study the interactive effects of gangliosides on growth and neuritogenesis in PC12 cells.
Target regulation of synaptic number in the expanded retinotectal projection of goldfish: the half-retinal preparation
Authors: Murray Marion , Sharma Sansar C.
Published: December 2019

The nature of the expansion of the visual field projection was studied in goldfish in which size disparities were created between the retina and the tectum. After removal of one-half of the retina, the remaining retinal ganglion cells expand their projections so that the entire contralateral optic tectum is encompassed (Schmidt et al.1978). We wished to determine whether this expansion is accompanied by increased arborization including proliferation of synaptic terminals by the spared retinal ganglion axons or whether field expansion is accomplished by increased arborization without changes in synaptic number. Portions of the retina were ablated and the animals were allowed to survive for at least 5 months, the time at which expansion can be demonstrated, before sacrifice. We mapped retinotectal projections to determine the extent of the expanded visual fields and used stereological and morphometric analyses of synaptic contacts in the retinal target lamina, the stratum fibrosum et griseum superficialis (SFGS), in the optic tectum to estimate synaptic number. Numbers of synaptic terminals in the SFGS contralateral to the lesioned retina were not different from numbers in the comparable portion of control tecta. These observations indicate that the surviving retinal axons increased the number of synaptic contacts on tectal target cells in response to removal of other retinal ganglion cells.
Calcitonin gene-related peptide (CGRP) in the regenerating rat sciatic nerve
Authors: Raivich G. , Dumoulin F.L. , Streit W.J. , Kreutzberg G.W.
Published: December 2019

Calcitonin-gene related peptide (CGRP) is a neuromodulatory peptide present in motoneurons and a subpopulation of sensory neurons of the adult peripheral nervous system. Here we have investigated the changes in axonal transport of CGRP and CGRP receptor expression in the injured and regenerating rat sciatic nerve using CGRP-immunocytochemistry, radioimmunoassay and quantitative in situ receptor autoradiography techniques. Axotomy led to a gradual and prolonged, 2.5- to 3.5-fold increase in specific CGRP binding to the distal part of the crushed sciatic nerve, beginning 4–6 days after axotomy. An even stronger, up to 30-fold increase was observed after 30–42 day denervation in the distal part of the transected sciatic nerve, where neurite reinnervation was prevented by retroversion and ligation of the proximal nerve stump. Reconnection of the proximal and distal nerve stumps 21 days after transection did not lead to a major reduction in specific CGRP binding but prevented a further increase that occurred between 21 and 42 days after transection without reconnection. In contrast, the anterograde axonal transport of CGRP decreased after axotomy to 40–50% of the control values 6–8 days after nerve crush but recovered towards normal levels during successful regeneration. Interestingly, the retrograde axonal transport of CGRP appeared to amount to only 10–20% of the anterograde transport, suggesting that the peptide may be released by the regenerating neurites into the endoneurium of the injured peripheral nerve. In view of the persistent upregulation in endoneural CGRP binding after axotomy these data indicate that axonal CGRP could play a regulatory role in mediating axonal–endoneural cell interaction during peripheral nerve regeneration.
Rehabilitation of homonymous scotomata in patients with postgeniculate damage of the visual system: saccadic compensation training
Authors: Kerkhoff G. , Münßinger U. , Haaf E. , Eberle-Strauss G. , Stögerer E.
Published: December 2019

A systematic training procedure for patients with disturbed visual search was evaluated in 92 patients with postchiasmatic visual field disorders (VFD) and 30 VFD patients with additional leftsided visual neglect (VFD +). Visual fields and areas of visual search via saccadic eye movements in the scotomatous field (search field) were mapped perimetrically in all patients before and after training and after a follow-up interval (mean follow-up interval: 22 months). A significant increase of more than 20° of visual angle was found in visual search field in the scotomatous field during training. Search field remained stable at follow-up in both patient groups. In contrast, only minor, though significant increases in visual field size were obtained during search field training in some patients. Multiple baseline designs in 5 patients revealed that search field enlargements were training dependent and not related to spontaneous recovery, adaptation to test procedures or measurement variability. VFD + Neglect patients needed some 25% more therapy sessions than VFD patients to achieve the same amount of increase in visual search field. Frequent head movements had a deleterious effect on training progress. It is concluded that the presented training procedure can lead to a significant and stable improvement in visual search within 15 to 25 training sessions and hence to a better compensation of visual deficits in daily living in most patients with VFD and/or visual neglect.
Differential sound-evoked metabolic activity in fetal tectum grafted into damaged adult rat inferior colliculus
Authors: Zrull Mark C. , Wessinger Terry M. , Coleman James R.
Published: December 2019

Long-Evans rats with unilateral lesions of the dorsal inferior colliculus (IC) received transplants of fetal tectal tissue to determine functional efficacy. Acoustic stimulation increases metabolic activity in both graft and host tissues relative to spontaneous activity in these regions. During periods of quiescence, graft tissue shows basal metabolic activity similar to that found in host IC. Coupled with previous anatomical findings, the results suggest that tectal grafts not only possess a neural structure resembling normal adult IC, but also contain cellular constituents which are responsive to sound. Given the apparent system-appropriate function of implanted fetal tectum, the graft tissue may be able to have a restorative effect within the damaged central auditory pathway.
GABA-ergic component of rat embryonic ventral mesencephalic grafts: an in-vitro study
Authors: Copray Jef C.V.M. , Vincent Arnaud J.P.E. , van Roon Willeke , Tomasini Ron , Staal Michiel J.
Published: December 2019

In order to establish the number, the viability and the developmental potential of GABAergic neurons present in dopaminergic ventral mesencephalic (VM) grafts from embryonic rat, we have studied the survival and development of these neurons in culture. The GABAergic fraction demonstrated a highly disproportionate survival in culture in relation to other VM neurons resulting in a drastic change in the neuronal composition of the dissociated VM grafts. The occurrence of a similar gradual dominance of GABAergic neurons at the site of intracerebral implantation, may affect the development of grafted dopaminergic VM neurons and their interaction with host striatal cells.
Muscle coordination in hindlimbs of mice after bilateral nerve regeneration
Authors: Kreischer Arno , Kleinebeckel Dieter , Klußmann Friedrich Wilhelm
Published: December 2019

The common peroneal nerve was transected bilaterally in 25 adult mice. Nerve stumps were immediately readapted without nerve suture. Before transection and after nerve regeneration the muscle coordination of tibialis anterior (TA) and medial gastrocnemius (MG) muscle was examined by electromyographic recordings from both muscles (EMG) during free running. Using a personal computer, the degree of muscle coordination between TA and MG was determined by calculating a coordination index. In normal mice an antagonistic innervation pattern was observed. After nerve transection and regeneration the degree of muscle coordination of TA and MG substantially decreased with great interindividual but also great intraindividual variation. In 16 mice there was no correlation between the coordination index of the left and right hindlimbs. In nine out of 25 mice reinnervation was absent on one side. These results suggest that nerve regeneration by axonal sprouting to appropriate or foreign muscles occurs at random and that there are no intraindividual factors which might promote the finding of the proper target muscle.
Repair of the transected rat sciatic nerve: matrix formation within implanted silicone tubes
Authors: Zhao Qing , Dahlin Lars B , Kanje Martin , Lundborg Göran
Published: December 2019

Matrix formation within silicone tubes of different geometries implanted between the stumps of the transected rat sciatic nerve was studied. A matrix, composed of longitudinally oriented fibrin strands containing fibronectin, was formed within one day. The matrix then increased in size. The matrix contained macrophages and other inflammatory cells. Matrix size could be increased if the diameter of the tube was increased or if holes were made in the implanted tube. In contrast, matrix diameter decreased if the tube length was increased or if circulation was compromised in the inserts. The results suggest that the size, orientation and cellular components of the matrix have profound effects on the regenerative response of the transected nerve.
Improvement of passive avoidance task after grafting of fetal striatal cell suspensions in ischemic striatum in the rat
Authors: Koide Kazuo , Hashitani Takeshi , Aihara Noritaka , Mabe Hideo , Nishino Hitoo
Published: December 2019

Behavioral recovery and cell survival/growth after grafting of fetal striatal cell suspensions in the ischemic striatum of rats were investigated. Ischemia was induced by one hour intraluminal occlusion of the right middle cerebral artery under halothane anesthesia. During the ischemia rats usually manifested signs of hemiparesis and sometimes rotations. Behavioral function was measured by a passive avoidance task and radial arm maze test at 1–2 weeks and 6–7 weeks after ischemia. The size of the ischemic lesions depended on each animal, but the ischemic animals showed deficits in both passive avoidance task and radial maze test. Two weeks after ischemia, fetal striatal cells, marked with DiI, were transplanted into the ischemic striatum. The transplantation improved the ischemia-induced deficit in the passive avoidance task but not in radial maze test. Although there were variations in the size of the grafts, many DiI-positive cells with dendritic outgrowth were detected under fluorescent microscopy. Immunohistochemical study revealed that many choline acetyltransferase (ChAT) positive cells and GABA-positive cells survived in the grafts. However, striosome-matrix compartments were not evident inside the grafts. Thus, partial recoveries in both cytoarchitectural and behavioral aspects were obtained by striatal cell grafts, suggesting that neural transplantation could be a useful approach in reconstructing ischemic brain function.
Pharmacological manipulation of the NMDA receptor differentially protects from systemic kainic acid neuropathology: evaluation through ornithine decarboxylase induction, morphology and GFAP immunohistochemistry
Authors: Guarnieri T. , Virgili M. , Villani L. , Facchinetti F. , Contestabile A. , Migani P.
Published: December 2019

The excitotoxic brain damage caused by systemic administration of kainic acid requires the activation of N-methyl-D-aspartate (NMDA) receptors in order to fully express its neurotoxic potency. We have tested the relative efficacy of different manipulations of the NMDA receptor on morphological, immunohistochemical and neurochemical parameters in this experimental model. A competitive (CGP 39551) and a non-competitive (MK 801) antagonist of the NMDA receptor, granted full protection against neuronal degeneration and consequent glial proliferation in the hippocampus and olfactory cortex, two regions severely affected by systemic administration of kainic acid. In addition, CGP 39551 completely counteracted the dramatic induction of the enzyme ornithine decarboxylase which occurs shortly after kainic acid administration. Systemic administration of high amounts of MgSO4 concomitantly and after kainic acid injection, appeared to partially prevent neuronal degeneration but had no clear effects on glial reaction and ornithine decarboxylase induction. Finally administration of an antagonist of the polyamine site present in the NMDA receptor (SL 82.0715), did not appear to have any protective effect at the dose used here. The present results help to better understand the ways by which it could be possible to counteract excitotoxic brain injuries.
Transplantation of dorsal root ganglion into the olfactory bulb of neonatal rats: a histochemical study
Authors: Sekerková Gabriela , Malatová Želmíra , Orendáčová Judita , Žigová Tatiana
Published: December 2019

We have transplanted encapsulated dorsal root ganglia (DRG) from adult Wistar albino rats unilaterally into partially bulbectomized (n = 20) neonatal (P3–5) rats of the same strain. Three months postoperatively the animals were perfused and their brains processed by direct thiocholine method for cholinesterases (Ch), specific acetylcholinesterase (AChE) and nonspecific butyrylcholinesterase (BuChE) or stained by Cresyl violet. Selected sections were immunohistochemically stained for olfactory marker protein (OMP). In 17 cases we found surviving transplanted DRG. Fifteen transplants were well integrated with the spared portion of the olfactory bulb (OB) as clearly demonstrated by AChE and BuChE histochemistry, while two did not integrate. Regenerated OMP positive olfactory axons originating from neuroepithelium and AChE positive fibres from OB remnant penetrated into the transplants. In one case, fibers connected with BuChE positive Schwann cells grew from the transplanted DRG into the host OB. Individual sensory neurons of the transplants revealed variable intensity of the AChE staining, thus resembling the pattern of AChE activity in normal DRG. BuChE activity was mostly localized on the surface of sensory neurons in the ring of satellite cells. Some BuChE positive blood vessels penetrated into the DRG, and were observed around sensory neurons. The results showed a considerable viability and adaptability of the sensory neurons in the new environment after a long-term transplantation.
Partial recovery of skilled forelimb reaching after transplantation of fetal cortical tissue in adult rats with motor cortex lesion – anatomical and functional aspects
Authors: Plumet Jocelyne , Ebrahimi Afsaneh , Guitet José , Roger Michel
Published: December 2019

We have studied the effect of transplantation of embryonic frontal cortex on the motor deficit resulting from motor cortex lesion in the adult rat. Twenty-four 2-month-old rats were first trained in a food reaching task with right and left forelimbs. Then, at 4 months of age, the subjects were divided into two equal groups. In the lesion group, the animals sustained a lesion of the left motor cortex, whereas in the graft group the animals received a fetal cell suspension of embryonic (E16) frontal cortical tissue three days after the lesion. Postoperative reaching ability was assessed every week during eight weeks and then every two months until the age of one year. The results indicate that the deficit resulting from the lesion is bilateral but mainly affects the limb contralateral to the lesion. During the first 3 weeks of postoperative testing, both groups displayed comparable evolution of performance with contralateral forelimb, characterized by an initial large drop followed by progressive recovery. But, whereas in the lesion group performance did not increase after the fourth postoperative week, in the graft group the reaching scores further improved, without recovering, however, preoperative levels. This improvement was still observed eight months after transplantation. However, no improvement appeared using the limb ipsilateral to the transplant. An anatomical study of the volumes of transplant and/or lesion revealed that the importance of the recovery or deficit varied as a function of the sizes of the transplant and/or lesion within the rostral part of the motor cortex, approximately corresponding to the rostral forelimb area of Neafsey et al. [37]. It is therefore suggested that in adult rats, some components of the motor deficit resulting from a lesion of the motor cortex can be partially reduced by transplantation of homotopic embryonic cortex.
Sprouting of axon-like processes from axotomized retinal ganglion cells is influenced by the distance of axotomy from the cell body and the mode of transplantation of the peripheral nerve
Authors: Cho Eric Yu Pang , So Kwok-Fai
Published: December 2019

It is a well known fact that the proximity of an axonal lesion from the cell body influences the degree of neuronal survival: a lesion close to the cell body leads to more severe cell death and vice versa. On the other hand, experiments involving transplantation of a peripheral nerve (PN) to various central nervous system (CNS) regions to induce axonal regeneration have suggested that axonal regrowth is more vigorous when the grafting is performed closer to the cell body. It is not clear, however, whether it is the distance of the site of axotomy or the location of the trophic source (PN graft) or both from the cell body which dictates the vigorousness of axonal regrowth. Using either a model of transplantation of a PN to the retina or implantation of a short PN into the vitreous body of the eye of the adult hamster, we have demonstrated that sprouting of axon-like processes from retinal ganglion cells (RGCs) depends on the distance of axotomy from the cell body when the PN graft is maintained at a constant distance from the cell body. Moreover, it was found that the distance of axotomy at which sprouting of axon-like processes could be induced was different for the 2 paradigms: with the intravitreal PN model, sprouting was observed even after intracranial ON cut whereas it was absent in the PN grafting-to-retina paradigm. This suggests that extrinsic influence (in this case an intravitreal PN) can overcome to a certain extent the growth-suppressive effects due to a long distance of axotomy.
Improved cryopreservative medium suitable for the freeze-storage and transplantation of fetal neural tissues
Authors: Yoshimoto Yusuke , Date Isao , Ohmoto Takashi
Published: December 2019

Techniques to maintain viable fetal neural tissue might be an important tool for a successful neural transplantation by giving enough time for preparation, storage, and transportation of donor tissue. In the present study, we examined the effect of freeze-storage (cryopreservation) for 7 days at liquid nitrogen temperature on the survivability of intraventricular rat fetal mesencephalic grafts (gestational day 15) when using 10% dimethyl sulfoxide (DMSO), 0.1% methylcellulose, or 10% DMSO with additional 0.1% methylcellulose (m-DMSO) as a cryoprotective agent. As a control group, the survivability of grafts transplanted immediately after dissection was examined. The volume of grafts treated with m-DMSO was 3 times as large as that of grafts treated with 10% DMSO alone. While the number of surviving neurons in 10% DMSO-treated transplants decreased down to 15% of the control value, there was no statistically significant difference in the number of surviving neurons between the m-DMSO treated group and control group. In the group treated with m-DMSO, there were a lot of well developed tyrosine hydroxylase positive neurons and fibers in the graft, and a few reactive astrocytes were observed only in the peripheral region of the grafts. In the group treated with 0.1% methylcellulose alone, no graft survival was observed in any of the animals. We conclude that the addition of methylcellulose to the commonly used cryoprotective agent (DMSO) is beneficial for the freeze-storage of fetal neural tissue.
4-Aminopyridine and spinal cord injury: a review
Authors: Hayes K.C.
Published: December 2019

Demyelination of axons within the spinal cord represents a significant component of the pathology of contusive and compressive spinal cord injury (SCI) and the associated conduction deficits most probably contribute to the paralysis and sensory loss experienced by SCI patients. 4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been shown capable of restoring conduction across demyelinated internodes in neurons of the spinal cord. Recent clinical trials of 4-AP provide evidence that limited and transient neurological gain may be derived by some SCI patients with longstanding injury. The present review traces the historical development of 4-AP, describes the mechanism of action and rationale for use in SCI, and provides an overview of the clinical trials conducted to date. The early trials give rise to optimism that pharmaceutical management of conduction deficits may have a role to play in restoring neurological function in some patients with SCI.
The role of the habenula-interpeduncular pathway in modulating levels of circulating adrenal hormones
Authors: Murray Marion , Murphy Carol A. , Ross L.L. , Haun Forrest
Published: December 2019

The fasciculus retroflexus (FR) is the major pathway by which the medial and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the habenula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronically, and habenula transplants have been shown to restore normal sleep patterns in rats [J. NeuroscL, 12 (1992) 3282–3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. When plasma samples were obtained via retro-orbital eye-bleed during anesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2–3 months postoperatively compared to unoperated controls. Transplants of embryonic habenula cells placed near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone levels. When plasma samples were obtained in conscious animals via indwelling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines were similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed method. Thus, the effect of FR lesions in increasing plasma levels of catecholamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While these results indicate that the integrity of the habenular efferent pathway is important in modulating circulating levels of hormones associated with the stress response, two separate mechanisms appear to control its interactions with sympathetic-adrenal medullary and adrenocortical pathways.
Recombinant basic fibroblast growth factor spares thalamic neurons from retrograde degeneration after ablation of the somatosensory cortex in rats
Authors: Kohmura Eiji , Yuguchi Takamichi , Yamada Kazuo , Sakaguchi Tateo , Hayakawa Toru
Published: December 2019

Retrograde degeneration of thalamic neurons after cortical ablation has long been recognized. Neuronal loss following axotomy eliminates the possibility of regeneration and might prevent the recovery from axonal injury in patients with brain trauma. We investigated whether CS23, a stable recombinant variant of human basic fibroblast growth factor (bFGF), could protect neurons from retrograde degeneration. Four weeks after ablation of the somatosensory cortex in young female rats, there was extensive neuronal degeneration and loss in the lateral ventro-posterior nucleus (VPL) of the ipsilateral thalamus. When Gelfoam soaked in bFGF(CS23) (1 μg/0.l ml) was applied topically at the time of surgery, this neuronal degeneration in the VPL was markedly reduced and macroscopic atrophy of the lateral and medial ventroposterior nucleus (VPL + VPM) was significantly reduced. In contrast, application of bFGF at three days after surgery failed to prevent retrograde degeneration. These resuts indicate that bFGF can prevent thalamic atrophy after ablation of the somatosensory cortex and that administration of bFGF is only effective in the very early period after brain injury.
Axonal regeneration in the foot branch of the superficial peroneal nerve and the lateral plantar nerve of the rat after sciatic nerve lesions
Authors: Povlsen B. , Stankovic N. , Danielsson P. , Hildebrand C.
Published: December 2019

Hand injuries with nerve lesions often leave the patient with a persistent sensory deficit, particularly with respect to glabrous skin. The present study examines axonal regeneration in the foot branch of the superficial peroneal nerve (fSPN) and the lateral plantar nerve (LPN), supplying hairy skin and glabrous skin together with some intrinsic muscles, respectively, after sciatic nerve lesions in the rat. Following crush lesions, the number of myelinated axons is normal in the fSPN, and the occurrence of C-fibers appears slightly reduced. In the LPN, the numbers of myelinated axons and C-fibers are both significantly increased. Post-crush regenerated myelinated fSPN and LPN axons show normal size ranges, but the proportion of small myelinated axons is increased. After neurotomy and suture, the numbers of myelinated axons and C-fibers in the fSPN are not significantly different from normal. The LPN exhibits a significantly increased number of myelinated axons, but the number of C-fibers is not significantly abnormal. In both nerves, the myelinated axons present an abnormally narrow size range. These findings show that the quantitative outcome of regeneration in a nerve innervating glabrous skin (and some intrinsic muscles) differs significantly from that of branches to hairy skin of the foot, with respect to myelinated as well as unmyelinated axons. To what extent these differences mirror functional differences awaits elucidation.
Experimentally induced autonomic neuropathy: beneficial effect of a systemic ACTH4-9 analogue on oculomotor nerve regeneration
Authors: Vandertop William P. , de Vries Willem B. , Notermans Nicolette C. , Tulleken Cees A.F. , Gispen Willem H.
Published: December 2019

While the regenerating capacity of peripheral nerves has been the subject of intensive study, little is known about the regenerative capacity of the autonomic nervous system. Using an animal model, where the pupil diameter of the eye in the rat serves as a parameter of autonomic function, we studied whether systemic treatment with the neuropeptide Org 2766, a synthetic ACTH4-9, analogue, facilitates the functional recovery of parasympathetic nerve fibres after transection, and after a crush lesion of the oculomotor nerve. By simply photographing the rat's pupil under standardised conditions, we show that sectioning the oculomotor nerve leads to an immediate mydriasis, followed by spontaneous regeneration in 30 days. Systemic treatment with an ACTH4-9 analogue had no effect on the rate or quality of recovery. However, systemic treatment with an ACTH4-9 analogue after a crush lesion of the oculomotor nerve (spontaneous regeneration time 16 days) did enhance the speed of recovery of the parasympathetic nerve fibres in the oculomotor nerve, especially in the initial stages of regeneration. We conclude that the animal model used in this study is valuable for studying the regenerative capacity of the autonomic nervous system and the influence of neurotrophic peptides on autonomic neuropathies. Evidence is presented that synthetic ACTH4-9 analogue exerts beneficial neurotrophic effects, not only in peripheral sensorimotor neuropathies but also in autonomic neuropathies.
Virus vectors for gene delivery to the nervous system
Authors: Smith Frances , Jacoby David , Breakefield Xandra O.
Published: December 2019

A number of virus vectors have been developed for gene delivery to the nervous system. Virus vectors still provide the most efficient means of gene delivery, and this is critical as only a small volume of inoculum can be used without damaging neurons. Each of the four types of vectors currently in use have their advantages and disadvantages. Highest titers can be achieved with herpes virus and adenovirus vectors, with retrovirus and adeno-associated virus (AAV) vectors currently yielding lower titers. The transgene capacity of each from highest to lowest is: herpes virus (30 kb), adenovirus (8–10 kb), retrovirus (7–8 kb) and AAV (4.5 kb). All can infect a broad range of cell types in the nervous system, including neurons, glia and endothelial cells. Herpes, adenovirus and AAV vectors can deliver genes to postmitotic, as well as mitotic cells, while retrovirus vectors depend on cell mitosis for gene delivery. Herpes virus can assume a stable extrachromosomal configuration in the nuclei of some neurons (termed latency), while both retrovirus and AAV can integrate into the cell genome. Both integrate at random sites, but AAV can also integrate at a specific chromosomal location. Adenovirus neither assumes a stable state nor integrates, still its genome can persist and be expressed in the host cell for some time (up to a month or so). Stability of gene expression is a problem for all the vectors, due in part to the use of viral promoters which tend to be down-regulated by the host cell over a month or so. Both herpes virus vectors and adenovirus vectors have some toxicity in their current configurations, while retrovirus and AAV tend to be associated with less neuropathogenicity. Many developments in vectors should be occurring over the next few years that should increase the potential of these vectors for therapeutic gene delivery.
Neurotrophic factors: repair and regeneration in the central nervous system
Authors: Varon Silvio S. , Conner James M. , Kuang Rong-Zhen
Published: December 2019

Neurotrophic factors promote maintenance, repair and regeneration of selected neurons in vitro and in vivo. They include nerve growth factor (NGF) and other neurotrophins, ciliary neurotrophic factor (CNTF) and other cytokines, and a number of growth factors. Molecular properties of the trophic proteins and their transducing receptors are increasingly well characterized. Interest in the neurotrophic factors has greatly accelerated over the past decade with accumulating evidence that they play important roles in the adult mammalian CNS as well as in its development. Adult in vivo models for degenerative CNS conditions have demonstrated the ability of exogenous neurotrophic factors (NTFs) to protect against neuronal damage induced by traumatic or chemical experimental lesions, particularly with regard to easily identifiable neurons such as cholinergic and dopaminergic ones. Other models have shown beneficial effects of NTF administration with regard to axonal regeneration inside CNS tissue.
Reactive changes in the adult rat superior colliculus after deafferentation
Authors: Wilms Pascale , Bähr Mathias
Published: December 2019

We have recently shown that optic nerve transection is followed by a delayed appearance (7–14 days after lesion) of putative guidance activities for retinal axons in the superior colliculus (SC) of adult rats. In the present study we analysed with immunohistological methods whether there is a correlation between localized reactive changes in the cellular compartment of the SC after deafferentation and the reappearance of putative guidance activities. The optic nerve of adult female Sprague–Dawley rats was transected. After 1 day to 1 year the contralateral SC was sectioned sagitally and examined with antibodies directed against Vimentin and glial fibrillary acidic protein (GFAP) to label astrocytes, myelin basic protein (MBP) to detect oligodendrocytes, OX-42 to stain microglia and SMI-31 to determine degeneration of afferent retinal ganglion cell axons. These stainings were performed in order to detect differences in the cellular composition of macro- and microglial cells between the anterior and posterior regions of the SC. All cell populations we examined in the SC showed reactive changes after optic nerve transection. Microglia activation occurred as soon as 2 days after optic nerve transection in the anterior part of the SC. After 4 days, a homogeneous distribution of activated microglia was seen in the whole SC. GFAP upregulation occurred without a specific regional distribution. Only Vimentin-expressing astrocytes appeared with a delay of 1–2 weeks after deafferentation and were strongly restricted to the afferent optic tract and the very anterior region of the SC. In conclusion, a temporo-spatial correlation between the re-expression of guidance activities and changes in the cellular compartment of the SC exists in the delayed re-expression of Vimentin in astrocytes and their strong spatial restriction. Activated microglia might be involved in triggering regional changes in an anterior-posterior graded fashion in the deafferented SC.
Functional N-methyl-D-aspartate receptors develop and persist in heterotopic cortical grafts and regulate expression of transcription factor KROX-24
Authors: Sommer Clemens , Bele Sylvia , Gass Peter , Kiessling Marika
Published: December 2019

N-Methyl-D-aspartate (NMDA) receptors are a major subfamily of glutamate receptors and thought to play a pivotal role in developmental plasticity and synaptogenesis, neuronal migration and differentiation. NMDA receptors have also been implicated in neuronal degeneration, as glutamate binding to the receptor initiates rapid excitotoxic signal transduction. Molecular cloning of cDNAs has yielded different NMDA receptor subtypes with an essential NR1 subunit associated with various modulatory NR2 subunits. The NR1 gene is expressed at high levels in virtually all brain structures, but to a distinctly higher extent in cortex than in striatum. Here we report on the development, maintenance and function of glutamate receptors in intrastriatally located cortical grafts. Cortical primordia of rat fetuses (El4) were stereotactically grafted into the rostral striatum of adult recipient rats. Expression of NR1 mRNA was examined by in situ hybridization after post transplantation periods of 2, 6 and 12 months. Analysis of NR1 mRNA expression in grafts after a differentiation period of 2 months revealed equal levels compared to the intact neocortex of the host rats and that of rats with the same ontogenetic age. No downregulation of NR1 mRNA was seen 6 and 12 months after transplantation. To ensure normal function of NMDA receptors in grafts, we studied the effects of a blockade of receptor dependent gene expression, using Krox-24 as a reporter gene. In normal brain tissue, constitutive expression of KROX-24 protein is thought to be maintained by NMDA receptor mediated physiological synaptic activity and can be abolished by the non-competitive NMDA receptor antagonist MK-801. Immunostaining of KROX-24 protein was almost identical in grafts compared to the corresponding neocortex. This constitutive expression of KROX-24 could be abolished by treatment with MK-801. Thus, our data indicate normal development and long term persistence of glutamate receptors with intrinsic excitatory activity in transplants.
Histologic assessment of sciatic nerve regeneration following resection and graft or tube repair in the mouse
Authors: Gómez Nuria , Cuadras Jordi , Butí Miquel , Navarro Xavier
Published: December 2019

The present study determines the number and morphology of myelinated fibers that regenerate after resection of the mouse sciatic nerve. In different groups of mice, a resection of 4 or 6 mm of the sciatic nerve was left unrepaired, repaired with silicone or collagen guides or by an autologous nerve graft of the same or smaller calibre. Regeneration was examined, under light microscopy, 3 months after operation and quantified by morphometric analysis of light micrographs of cross-sectional nerve fibers. The results show that, without repair, few nerve fibers reach the distal nerve stump, while tubulization or autografts allowed better regeneration. Tube repair allowed a comparable degree of regeneration to that of an autograft with 4 mm gaps, but lower with 6 mm gaps. Regeneration was limited with a gap of 6 mm in silicone tubes, but was successful in half the mice with collagen tubes. The size and myelination of regenerated fibers were below normal values in all experimental groups, although they were closer to normal with sciatic autografts than after smaller grafts and tubulization. There were no signs of secondary degeneration in the nerve regenerates within silicone and collagen tubes. © 1996 Elsevier Science Ireland Ltd. All rights reserved
Transcutaneous electrical stimulation of the neck muscles and hemineglect rehabilitation
Authors: Pizzamiglio L. , Vallar G. , Magnotti L.
Published: December 2019

In four patients with left visuo-spatial hemineglect and right brain- damage, the therapeutic effects of Transcutaneous Electrical Nervous Stimulation (TENS) of the left neck muscles, associated with a non-specific treatment, and of a specific rehabilitation paradigm were investigated. The two treatments were given for an 8-week period each. TENS had positive effects on hemineglect in two out of four patients, whereas the specific treatment produced a major improvement of the disorder in all four cases. The suggestion is made that an effective treatment of neglect requires a paradigm comprising a range of visuo-spatial exploratory tasks of increasing complexity and a systematic feedback as to the success of the patients' performance. This is the case of the specific treatment. By contrast a procedure confined to a sensory stimulation, which produces a short-term improvement in the range of minutes, does not have comparable long-term effects. © 1996 Elsevier Science Ireland Ltd. All rights reserved