bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial effect of the opioid receptor antagonist naltrexone on hyper-sensitivity induced by spinal cord ischemia in rats: disassociation with MK-801
Authors: Hao J.-X. , Xu X.-J. , Aldskogius H. , Seiger Å. , Wiesenfeld-Hallin Z.
Published: December 2019

In this study we examined the effect of the long-acting opioid antagonist naltrexone on the allodynia-like effect of spinal ischemia in rats. The spinal cord ischemia was induced at midthoracic level by a recently developed photochemical technique using laser irradiation and photoactivatable intravascular dyes. An allodynia-like sensory disturbance, where the animals reacted by vocalization to non-noxious mechanical stimuli in the flank area, was consistently seen during several days after ischemia. Pretreatment with 10 and 20 mg/kg, but not 5 mg/kg naltrexone i.v. 10 min before irradiation decreased the incidence of allodynia. However, even the effect of the highest dose of naltrexone (20 mg/kg) was incomplete, which is in contrast to the effect of the NMDA receptor antagonist MK-801, which has been tested in the same model and found to completely prevent the incidence of allodynia at a dose of 0.5 mg/kg. Pretreatment with sub- or suprathreshold doses of naltrexone (5 and 20 mg/kg respectively) combined with a subthreshold dose of MK-801 (0.1 mg/kg) did not produce a synergistic effect. When naltrexone (20 mg/kg) was administered 10 min after induction of ischemia, it was totally ineffective in decreasing the occurrence and severity of allodynia. In contrast, MK-801 (0.5 mg/kg) still had a good protective effect when injected as this time. Histological examination showed slight morphological damage in the spinal cord in 38% of control rats after 1 min laser irradiation without pretreatment with naltrexone. No morphological abnormalities were observed in rats after pretreatment with naltrexone (20 mg/kg). The results suggest that opioid receptor antagonists and NMDA receptor antagonists prevent a consequence of transient spinal cord ischemia through different mechanisms. High doses of opioid antagonists may have anti-ischemic effects by improving local spinal cord microcirculation and therefore may have a role in preventing ischemia after traumatic spinal cord injury. On the other hand, the NMDA receptor may have a role in the secondary neuronal death resulting from ischemia. Thus, NMDA receptor antagonists may contribute to the prevention of tissue damage by antagonizing the excitotoxic action of glutamate and/or aspartate released by ischemia into the spinal cord. Finally, since only high doses of naltrexone had an effect in the present study, we cannot rule out the possiblity that this drug may act through non-opioid mechanisms.
α-Noradrenergic agonists and antagonists affect recovery and maintenance of beam-walking ability after sensorimotor cortex ablation in the rat
Authors: Sutton Richard L. , Feeney Dennis M.
Published: December 2019

Rats trained to traverse a narrow elevated beam were given a single intraperitoneal injection of either D-amphetamine, clonidine, L-phenylephrine, prazosin, yohimbine, or saline 24 h after ablation of the right sensorimotor cortex and tested for recovery of beam-walking (BW) ability to day 16 postsurgery. Clonidine, prazosin and L-phenylephrine did not significantly affect BW recovery. A 10 mg/kg dose of yohimbine significantly accelerated BW recovery, as did D-amphetamine (2 mg/kg). Since D-amphetamine and yohimbine both increase norepinephrine (NE) release and prior research has implicated NE but not dopamine in BW recovery, these data support the hypothesis that increased NE release benefits functional recovery in this model of cortical injury. However, a possible role of dopaminergic or serotonergic influences of D-amphetamine or yohimbine treatment cannot be ruled out. To investigate the role of the NE system in maintenance of recovery, animals recovered from BW deficits 18 days after injury were administered clonidine, prazosin, or yohimbine and retested on the BW task. Both the α1-NE antagonist prazosin (2 or 4 mg/kg) and the α2-NE agonist clonidine (0.1 or 0.4 mg/kg) produced a dose-dependent, transient worsening of BW performance. This reinstatement of deficits in recovered rats suggests that integrity of the α-NE system is necessary for maintaining functional recovery.
Axonal projections and functional recovery following fascicular repair of the rat sciatic nerve with Y-tunnelled silicone chambers
Authors: Zhao Qing , Dahlin Lars B. , Kanje Martin , Lundborg Göran , Lu Shi-Bi
Published: December 2019

The projection of regenerating axons and the specificity of motor reinnervation were studied after repair of the transected rat sciatic nerve with Y-tunnelled silicone chambers. This geometry was used experimentally to face either the proximal tibial or peroneal fascicle with two distal fascicular options usually the distal peroneal and tibial fascicle. A 4 mm gap separated the proximal and distal fascicles. Four weeks after the repair, preferential motor reinnervation could be demonstrated and there were always more axons projecting towards the distal homonymous fascicle. In contrast, if the distal stumps were disconnected from the target no fascicle specific projection of axons was observed. This was true even if segments from the median and ulnar nerve were used to replace either the distal tibial or peroneal segments. It appeared as though the size and not the type of fascicle determined the number of attracted axons. The results suggest that there is no fascicle specific guidance of regenerating nerve fibers.
Phenotypic plasticity of ‘mature’ human fœtal mesencephalic dopaminergic neurons and glial cells
Authors: Detta Allah , Grabham Peter , Hitchcock Edward
Published: December 2019

Human mesencephalic neurons from the second trimester have been cultured and characterised. Fresh, non-cultured cells were rounded and without processes post-dispersion but in culture differentiated with neurite outgrowth when treated with 2 mMdibutyryl cyclic AMP in the absence of serum. This morphological differentiation could be reversed by the addition of the serine protease, prothrombin. Immunocytochemical staining for dopamine, tyrosine hydroxylase, neuron-specific enolase and glial fibrillary acid protein, demonstrated that dopaminergic, non-dopaminergic and glial elements responded similarly. The conditioned medium contained quantifiable levels of catecholamines as measured by HPLC. These findings are relevant to both developmental neurobiology and clinical neural transplantation, evidencing the considerable plasticity and functional integrity of mesencephalic cells in the second trimester as well as the influence of environmental factors.
Correlation between vestibular habituation and postural recovery in cerebellar patients
Authors: Suarez H. , Caffa C. , Macadar O.
Published: December 2019

Vestibular habituation was studied in normal subjects and in patients with cerebellar disease using a stimulation paradigm proposed in this paper. Six caloric stimuli were repeated daily in the same ear during six days and electronystagmographic responses at the beginning and the end of that period were compared. The normal behaviour was a clear reduction of the response across time. Two groups of cerebellar patients were identified by their ability to recover from positional imbalance after treatment. Compensated patients responded to repeated caloric stimulation in the same way as normal subjects. Conversely, uncompensated patients increased their response after the stimulation paradigm. The role played by the cerebellum in vestibular plasticity is discussed together with the observed correlation between vestibular habituation and the ability for postural recovery to occur.
Axonal regeneration after peripheral nerve grafting and fibrin–fibronectin-containing matrix implantation on the injured septohippocampal pathway of the adult rat: a light and electron microscopic study
Authors: Knoops Bernard , Ponsar Cécile , Hubert Isabelle , van den Bosch de Aguilar Philippe
Published: December 2019

The damaged septohippocampal pathway was utilized to study the axonal regeneration of injured neurons. Semipermeable tubes, 2-mm long, were placed in the axis of the transected septohippocampal pathway of adult rats. In a first series of experiments, empty tubes were implanted. Even six weeks after the operation, no regenerated axons were observed in the conduit. In a second series of experiments, in order to validate our approach, segments of pre-degenerated sciatic nerves were introduced into the tubes. Under these experimental conditions, acetylcholinesterase (AChE)-containing regenerated axonal processes were detected in the grafted sciatic nerves. Glial fibrillary acidic protein (GFAP)-immunodetection showed that astroglial cells and astrocyte processes were able to progress on and into the peripheral grafts. At the electron microscopic level, axons were observed in close contact with Schwann cells which myelinated some of them. In some other cases, unmyelinated axons were also present at the surface of reactive astroglial cells filled by numerous intermediate filaments. These central glial cells had migrated among the sciatic nerve collagen fibers. No axon was detected without glial cell contact. In a third series of experiments, we implanted semipermeable tubes previously filled with a fibrin–fibronectin-containing matrix provided by peripheral regeneration chambers. One week after the implantation of the tubes containing this peripheral substrate, different cell types were observed migrating into the conduit and replacing the fibrin–fibronectin-containing matrix. Among these cells astrocytes were present as revealed by GFAP-immunocytochemistry and electron microscopic examinations. During the following weeks, axons were detected in contact with the reactive astroglial cells. AChE-histochemistry showed that axons were able to cross the two millimeter distance separating the septal part and the hippocampal part of the lesion site. GABA (γ-aminobutyric acid)-ergic fibers were also detected in the regenerated structure. These experiments show that cellular or acellular substrates provided by the PNS can promote the regeneration of CNS GABAergic and cholinergic neurons. Our observations suggest that astrocytes can take an important part, after their migration or after extending processes, in the axonal regeneration in the adult CNS of the rat, possibly in furnishing a cellular terrain for the progression of growth cones over a distance of two millimeters and in maintaining regenerated axons at least until the sixth week after the operation.
Characteristics of the vibratory reflex in humans with reduced suprasegmental influence due to spinal cord injury
Authors: Sherwood A.M. , Dimitrijevic M.R. , Bacia T. , McKay W.B.
Published: December 2019

The tonic stretch reflex elicited by vibration of a muscle or tendon provides a means of studying segmental reflex activity in humans with impaired volitional motor activity due to spinal cord injury (SCI). Vibration applied to the achilles or patellar tendon in a group of 51 SCI subjects elicited motor unit activity different from that found in 12 healthy subjects. Four distinct features of motor unit responses to vibration of a single tendon (achilles or patellar) could be seen in the SCI subjects: (i) a rapid onset, tonic response, frequently beginning with a single burst analogous to a tendon jerk, in 72% of vibrated sites; (ii) repetitive, phasic bursts of activity or vibratory-induced clonus in 23% of the tonic responses; (iii) spread of activity to muscles distant from the vibration in 44% of the tonic responses; and vibratory-induced withdrawal reflexes (VWR) which occurred after vibration of 37% of the sites. Overall, 81% of stimulated sites responded to vibration in SCI subjects. In contrast, only 54% of vibrated sites responded in control subjects, always with a gradual onset tonic response, never accompanied by a VWR. The VWR in SCI subjects was typically of much larger amplitude than the tonic responses and involved a mean of 5 muscles (41% bilaterally). Features of these responses provide an insight into underlying neurocontrol mechanisms which may provide guidance in the selection of appropriate intervention or management strategies.
The effect of a short-course treatment with FK506 on the survivability of rat-to-mouse cross-species neural graft
Authors: Sakai Kyoji , Yoshimoto Yusuke , Date Isao
Published: December 2019

We examined the effect of a short-course treatment with a new immunosuppressive agent FK506 (FK) on the survivability of neural xenografts. Pieces of ventral mesencephalic tissues from rat embryos were transplanted into the right lateral ventricle of adult mice. The mice were either assigned to a 4-day FK (10 mg/kg/day) immunosuppressive scheme or were given no immunosuppression. The 4-day course treatment with FK was started on postoperative day 0, 2, 4, 6 or 8. The incidence of graft rejection 28 days after transplantation was 82%, 55%, 55%, 100% and 100% when FK was given on days 0–3, 2–5, 4–7, 6–9 and 8–11, respectively. As a separate group, we examined the cellular infiltration in neural xenografts of the non-immunosuppressed recipients at two different time points (3 days and 7 days) after transplantation. The infiltration of T-lymphocytes was not detected 3 days after transplantation, but had occurred by 7 days after transplantation. We speculate that FK is more effective in preventing the rejection of neural xenografts when it is given just before the initiation of the T-lymphocytic infiltration.
The regeneration of axons through normal and reversed peripheral nerve grafts
Authors: Ansselin Annick D. , Davey David F.
Published: December 2019

The effect of proximo-distal orientation of peripheral nerve grafts upon axonal regeneration has been investigated using the sciatic nerve of the rat as a model. To test the hypothesis that the presence of nerve branches within a graft will cause misdirection of axons in normally oriented grafts but not in reversed grafts, all grafts studied contained branches. Qualitative electron microscopic examination of graft ultrastructure revealed no differences in nerve structure related to graft orientation. In most normally oriented grafts, branches persisted up to 12 months after surgery. These branches contained axons which terminated at the end of the branch. In all reverse oriented grafts, and in a small number of normally oriented ones, the branches could not be seen after two or more months of regeneration. Axons sprouting outside of the epineurium of the graft caused the branch to be incorporated into the nerve structure. Axon counts in the distal stump of grafted nerves after twelve months recovery revealed that normally oriented grafts with persistent branches led to poorer peripheral regeneration, especially of unmyelinated fibers. The results indicate that regeneration of axons to their peripheral targets may be facilitated by reversing the graft orientation.
Visualization of outgrowing axons of grafted neurons by anterograde labelling with Phaseolus vulgaris leucoagglutinin in the motor cortex of the rat
Authors: Senatorov Vladimir V. , Nyakas Csaba , Fulop Zoltan
Published: December 2019

Fetal cerebral cortical tissue was transplanted into an aspirated lesion cavity made in the sensorimotor cortex of adult rats. Ten weeks after grafting, outgrowing fibers from the graft were visualized by an anterograde tracing technique using Phaseolus vulgaris leucoagglutinin (PHA-L). It was demonstrated that the efferent fibers grew into the neighboring host cortical tissue, the corpus callosum and in some cases approached caudate/putamen. Characteristic axon arborization with abundant boutons were found in the host cortical tissue, but only in close vicinity to the grafts. It is concluded that the PHA-L anterograde tracing technique can be a useful tool to assess the degree of anatomical integration of the transplants into the host tissue.
Effects of microglia-derived cytokines on astrocyte proliferation
Authors: Suzumura Akio , Sawada Makoto , Mokuno Kenji , Kato Kanefusa , Marunouchi Tohru , Yamamoto Hiroko
Published: December 2019

Recent studies have suggested that cytokines, such as interleukin-l(IL-l), tumor necrosis factor(TNF)α, or interferon(IFN) γ, play a role in the development of astrocytic gliosis. In this study, we examined the effects of these cytokines on the proliferation of purified astrocytes in vitro, using the colorimetric assay, bromodeoxyuridine uptake by astrocytes, and changes in the amount of the S-100 β protein as markers of astrocyte proliferation. The effects of a crude supernatant from microglia enriched cultures (Mi-Sup) also were examined. In contrast to previous reports, these recombinant cytokines did not induce proliferation of purified mouse astrocytes. However, stimulation of astrocytes with Mi-Sup increased all the markers for astrocyte proliferation, which could not be blocked by the addition of anti-IL-1, IL-6, IFNγ or TGFβ antibodies. Thus, it appears that microglia produce factors, other than the above cytokines, which induce the proliferation of astrocytes in vitro. These factors may have a role in the development of gliosis in various pathologic conditions of the central nervous system.
Synthetic nerve graft containing collagen and synthetic Schwann cells inproves functional, electrophysiological, and histological parameters of peripheral nerve regeneration
Authors: Keeley Robert , Atagi Tanya , Sabelman Eric , Padilla Jose , Kadlcik Paula , Agras Jean , Eng Lawrence , Wiedman Tien-Wen , Nguyen Khoi , Sudekum Anthony , Rosen Joseph
Published: December 2019

Current methods of peripheral nerve repair are to directly suture cut nerve stumps, or to bridge large gaps with an autograft repair. Autograft-associated problems include donor site morbidity and limited supply. Many of the present limitations of nerve repair might be overcome by expanding the patients own Schwann cells in vitro, then combining the cells with other neuro-tropic and -trophic materials into an Artificial Nerve Graft (ANG) for bridging a nerve gap. In this 4.5 month experiment, a rat peroneal nerve model with a 10 mm gap was used to evaluate the effect of live Schwann cells on peripheral nerve regeneration. Nerve gaps were repaired with cellular ANGs containing live Schwann cell, dead Schwann cell, or mixed fibroblast/Schwann cell populations suspended in a collagen I matrix, and with sutured autografts or ANGs containing just collagen or medium. Regenerated nerves were evaluated by walking track analysis, qualitative and quantitative histology, and electrophysiology. Overall, the autograft was the best repair method, while the ANG containing live Schwann cells was statistically superior to other ANG repair methods. This study demonstrates that an ANG containing cultured syngeneic Schwann cells improves functional, histological, and electrophysiological parameters of peripheral nerve regeneration.
Transient improvement of amphetamine-induced rotational behavior by PC12 cell grafts: studies with microdialysis
Authors: Hori Yozo , Kageyama Hiroyasu , Kihara Tsuyoshi , Ikeda Masato , Nakano Akira , Kurosawa Atsushi
Published: December 2019

The effects of striatal transplantation of PC12 cells on amphetamine-induced rotational behavior and monoamine levels were examined in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal pathway. A total of 9 × 104 or 9 × 105 cells of PC12 was implanted into 3 sites in the striatum and changes in amphetamine (3 mg/kg, i.p.)-induced rotational behavior were observed for 8 weeks. Two weeks after transplantation, a significant reduction in rotation was observed. However, this improvement disappeared after 3 weeks. Three of 7 rats implanted with 9 × 104 cells and 6 of 7 rats with 9 × 105 cells died between 3 and 4 weeks after transplantation. In 6-OHDA-injected control rats, the levels of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in brain dialysates were profoundly reduced to between 0 and 11% of normal rats, while the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level remained unchanged. These reductions in DA and its metabolites did not recover at 2 or 8 weeks after the transplantation of 9 × 104 PC12 cells. 5-HIAA was reduced at 2 weeks and recovered to nearly control levels at 8 weeks. Histologically, PC12 cells proliferated to form a large tumor mass at 2 weeks. There were almost no processes growing from the aggregated PC12 cells into the host tissue. These results indicate that PC12 grafts do not release detectable quantities of DA into the deafferented striatum, and suggest that the transient improvements in rotational behavior may be due to a non-specific suppression in neuronal function induced by the growing tumor mass.
Experimental hyperthyroidism enhances the regeneration of central neurites promoted by peripheral nerve grafts in the hippocampus
Authors: Lewin-Kowalik Joanna , Koksanowicz Ewa , Barski Jarosław-Jerzy , Krause Mieczysław , Górka Dariusz , Gołka Beata , Kwiek Stanisław
Published: December 2019

The aim of the present paper was to ascertain whether experimental hyperthyroidism promotes the regenerative action of predegenerated peripheral nerve grafts implanted into the transected hippocampus. Hyperthyroidism was induced by subcutaneous injections of T4. Autologous peripheral nerve grafts were implanted immediately, 7 and 35 days following transection of the sciatic nerve. Cells extending their neurites into the grafts were traced by means of horseradish peroxidase conjugated with fluoresceine isothiocyanate (FITC-HRP). Fluorescence microscope examination revealed that experimentally induced hyperthyroidism considerably enhanced the regenerative influence of peripheral nerve grafts. This effect was particularly pronounced in hyperthyrotic animals treated with either nonpredegenerated or 35 day predegenerated nerve grafts.
The effect of propranolol on the desipramine-induced regeneration of brain noradrenergic axons in the rat
Authors: Nakamura S.
Published: December 2019

The antagonizing effect of the β-adrenoceptor antagonist propranolol (PRP) on the desipramine (DMI)-induced regeneration of brain noradrenergic fibers was examined. The symmetrical sites of the rat frontal cortex were pretreated with 6-hydroxydopamine (6-OHDA). Then, the same cortical site of one hemisphere was infused with DMI, while the corresponding site of the other hemisphere was infused with DMI (1 mM) plus PRP (1 mM). The DMI-induced axonal regeneration was attenuated by PRP. This finding suggests that activation of β-adrenoceptors is involved at least in part in the regeneration of brain noradrenergic axons.
The effects of delayed nerve repair on nerve regeneration in a silicone chamber model
Authors: Danielsen Nils , Johansson Bengt R. , Dahlin Lars B.
Published: December 2019

The silicone chamber model for nerve regeneration is suitable to test the effects of exogenous agents or surgical manipulations on nerve regeneration. The total 16-day regeneration period used in this model makes it possible to analyze the effects of certain manipulations on the sequential advancement of the individual cellular components (circumferential perineurial-like cells, vessels, Schwann cells, axons, and myelin) into the chamber fibrin matrix. In the present study we compared the effects on cellular migration of a 7 day delayed chamber repair vs. chamber repair immediately after transection (control chambers) of the rat sciatic nerve. Regeneration was evaluated with light and electron microscopic techniques. Chambers implanted after a delay of 7 days had a statistically significant more advanced migration of vessels, Schwann cells, and axons from the proximal nerve stump and also a significantly increased vascular density as compared to control chambers. We conclude that a 7 day delayed nerve repair stimulates nerve regeneration in this specific silicone chamber model.
Production of terminally differentiated neuroblastoma cells in culture
Authors: Prasad Kedar N. , Carvalho Erika , Kentroti Susan , Edwards-Prasad Judith , La Rosa Francisco G. , Kumar Sanjay , Freed Curt R. , Vernadakis A.
Published: December 2019

The use of fetal central nervous system (CNS) tissue in neural transplants has ethical, availability and some biological limitations. In order to overcome these problems, homogeneous populations of specific neurons in vitro should be established. Transformed nerve cells such as neuroblastoma cells (NBP2) in culture can serve as one of the sources of donor neurons in neural transplants provided they can be induced to differentiate terminally. This study showed that treatment of murine neuroblastoma (NBP2) cells with 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724, an inhibitor of cyclic nucleotide phosphodiesterase), and β-carotene for a period of 3 days followed by X-irradiation with 20 Gy or above produced 100% terminally differentiated cells. These differentiated NB cells had long and extensive neurites, contained elevated levels of tyrosine hydroxylase (TH) activity and very low levels of MHC class I and II antigens, and were non-tumorigenic. The viability of differentiated NB cells when determined on the criteria of attachment efficiency, re-extension of neurites and presence of TH after replating was only 9%. This was in contrast to the trypan blue exclusion technique which showed that over 90% of differentiated NB cells in culture were viable.
Expression of basic fibroblast growth factor receptor messenger RNA in the periinfarcted brain tissue
Authors: Sakaguchi Tateo , Yamada Kazuo , Wanaka Akio , Kohmura Eiji , Yuguchi Takamichi , Taneda Mamoru , Kataoka Kazuo , Tohyama Masaya , Hayakawa Toru
Published: December 2019

The present study examined whether expression of basic fibroblast growth factor receptor (bFGFR) messenger ribonucleic acid (mRNA) was upregulated by focal ischemia. We have studied the in situ hybridization autoradiography for bFGFR mRNA in the rat model of middle cerebral artery (MCA) occlusion. Male Wistar rats were used for occlusion of the left MCA, and were sacrificed 1, 3, 7 and 14 days after MCA occlusion. In situ hybridization was performed on the brain sections of these animals and sham controls by using 35S-labeled antisense and sense (control) RNA probes for rat bFGFR. Expression of bFGFR mRNA was observed in the periinfarcted area of the rats within 1-14 days after MCA occlusion. Expression was evident in the whole hemisphere of the infarcted side, especially at 1 and 3 days after ischemia, but no expression was detected in the contralateral side. On microautoradiograms, the signals of bFGFR mRNA were detected in both neurons and non-neural cells located in the periinfarcted area. Upregulation of bFGFR mRNA detected in the periinfarcted brain tissue suggests that receptor-mediated action of bFGF may be related to preservation of neurons injured by ischemia.
Proliferation and differentiation of transplanted embryonic diencephalon in the brain of adult rats
Authors: Ikeda Hidetoshi , Asser Toomas , Yoshimoto Takashi
Published: December 2019

The survival, proliferation potential, differentiation, and host tissue reaction of allografts of undifferentiated embryonal diencephalic tissue (E12.5, E17.5) transplanted into or around the third ventricle of adult rats were investigated. Rats harboring grafts were sacrificed at three, six, and nine weeks after transplantation. The proliferative activity of the grafts was assessed by injection of 5′-bromo-2′-deoxyuridine (BrdU) into pregnant rats before the removal of fetuses for transplantation, and staining the grafts using an anti-BrdU antibody. The proliferative activity of the transplanted grafts was evaluated by immunostaining using an anti-proliferating cell nuclear antigen (PCNA) antibody. The differentiation of the grafts into neurons was estimated by double immunostaining using anti-BrdU and anti-neuron-specific enolase (NSE) antibodies. The survival rate of the grafts was strongly related to the proliferative activity of the graft. Surviving E17.5 grafts contained immunoreactive BrdU cells. E12.5 grafts could survive without immunoreactive BrdU cells. Undifferentiated El2.5 grafts proliferated up to six weeks after transplantation. Thereafter, most graft cells differentiated into mature neurons. E12.5 diencephalic allografts survived well with minimal rejection reactions and resulted in substantial neurite ingrowth into the host brain, while El7.5 allografts caused substantial reactive gliosis and little ingrowth.
Continuous low amplitude direct current stimulation of the crushed peripheral nerve accelerates the early recovery of choline acetyltransferase but not of acetylcholinesterase activity in fast and slow muscles
Authors: Ribarič Samo , Cvirn Pavel , Stefanovska Aneta
Published: December 2019

We investigated if continuous 1 µA direct current stimulation of the injured nerve, with the cathode electrode at the distal end of the nerve crush injury (cathode stimulation), accelerated the recovery of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity in transiently denervated extensor digitorum longus (EDL) and soleus (SOL) rat muscles. ChAT is a specific marker of cholinergic nerve terminals and may reflect axon ingrowth, and AChE reflects the re-establishment of neuromuscular junctions and recovery of muscle activity. Compared to sham operated animals, the cathode (CA) stimulated rats had a statistically significant larger ChAT activity in the EDL and SOL muscles on days 12 and 14 after nerve crush (P < 0.01, n = 6). The difference in ChAT activity between the groups decreased thereafter. Regarding recovery of muscle AChE, CA stimulation of the crushed sciatic nerve did not detectably accelerate the normalization of activity and pattern of AChE molecular forms in the EDL and SOL muscles. This means that the early rise in ChAT muscle activity in CA stimulated rats was not followed by an accelerated normalization of the neuromuscular transmission in the same group. It is more likely that the higher ChAT activity observed after cathode stimulation indicates a higher ChAT content in regenerating motor nerve endings, rather than a greater number of motor axons entering the muscles. It seems possible that cathode stimulation increased ChAT axonal transport, causing the early increase of ChAT content in the nerve endings. This raises the possibility that the axon transport and subsequent secretion of a trophic factor(s) from the nerve to the reinnervated muscle are enhanced as well, thus shortening the overall time of muscle force recovery in the absence of an appreciable acceleration of recovery of the neuromuscular transmission.
Differential recovery of bipedal and overground locomotion following complete spinal cord hemisection in cats
Authors: Michele Basso D. , Murray Marion , Goldberger Michael E.
Published: December 2019

We used behavioral assessment techniques to investigate the recovery of locomotion after spinal cord injury. Complete hemisec-tions were made at T13 and LI in the cat spinal cord. Observational and high-speed kinematic analyses of bipedal treadmill and overground locomotion were made from 1 to 5 weeks postoperatively. Both bipedal and overground locomotion showed partial recovery. The early stage of recovery was characterized by an increased range of joint movement in a proximal to distal progression. During later stages, hindlimb movements became more complex and interjoint coordination markedly improved. Overground locomotion recovered faster and to a greater extent than bipedal locomotion, as indicated by the time course of recovery, joint angular excursions and intralimb coordination. We propose that the recovery of bipedal locomotion may be more limited by reorganization of segmenta) sensory systems than overground locomotion, perhaps because alternate strategies for overground locomotion are available.
Pruning of dendrites and restoration of function after brain damage: Role of the NMDA receptor
Authors: Kozlowski D.A. , Jones T.A. , Schallert T.
Published: December 2019

Following unilateral injury to the forelimb-representation area of the sensorimotor cortex (FL-SMC) in adult rats, there occurs a biphasic process of overgrowth and partial elimination of neuronal dendrites in layer V pyramidal cells of the homotopic cortex of the opposite hemisphere. These neural events are associated with hyper-reliance on the non-impaired forelimb for postural-supporting and related movements that compensate for impaired function in the other forelimb. The overgrowth appears to be use-dependent because it can be prevented by one-sleeve casts that restrict the range of movements of the unimpaired limb during the period of expected neural growth. In development, “exuberant” growth of neurons is often followed by pruning, a process that has been associated with activity-dependency and a glutamatergic N-methyl-D-aspartate (NMDA) mechanism. To determine whether a related mechanism might be operating in adult animals recovering from brain damage, MK-801, a non-competitive NMDA receptor antagonist, was administered during the pruning phase in adult rats that had sustained FL-SMC lesions. MK-801 prevented the elimination of dendrites in the FL-SMC rats and had no effect on dendritic arborization in Sham-operated rats. MK-801 reinstated dysfunction in the previously-recovered forelimb in FL-SMC rats, and had no effect in Sham-operated rats. These data are consistent with the possibility that there may be a functionally important pruning mechanism with a glutamatergic component in adults with FL-SMC lesions, just as in the developing brain.
Internalization of macromolecules by live cells
Authors: Derossi D. , Prochiantz A.
Published: December 2019

The membrane of eukaryotic cells represents a barrier normally impermeable to non-lipophilic substances. In consequence, internalization of extracellular compounds requires the presence of specific channels, or of specialized endocytic mechanisms. Recently, several groups have reported that some growth factors and transcription factors can be internalized by cells in culture and addressed to the cytoplasmic and nuclear compartments. In the latter case, they have been shown to interfere directly with gene transcription. Among these factors are fibroblast growth factor-1 and -2 (FGF-1 and FGF-2), schwannoma-derived growth factor (SDGF), Tat protein and homeodomain or homeodomain containing polypeptides. In the present paper, we present the available data concerning these unconventional uptake mechanisms and speculate on their potential interest to target macromolec-ular structures into live cells.
Does monocular viewing improve target detection in hemispatial neglect?
Authors: Serfaty C. , Soroker N. , Glicksohn J. , Sepkuti J. , Myslobodsky M.S.
Published: December 2019

Experimental animals with large posterior-cortical lesions develop disturbances of visual perception and visually-guided behavior in the contralateral space, resembling the syndrome of unilateral spatial neglect (USN) in humans. The visuo-motor performance in the ignored space is recovered some time following additional lesion inflicted to the contralesional superior colliculus (SC) or section of the intercollicular pathways. Based on the model that explains this recovery by disinhibition of the ipsilesional SC (the ‘Sprague effect’) Posner and Rafal [37] proposed that ipsilesional monocular occlusion could possibly reduce the ‘tone’ of contralesional collicular neurons thereby removing an important contributor of hemineglect. A group of twenty-six right-hemisphere-damaged patients with USN was given a cancellation task under binocular and monocular (left and right) viewing conditions. Thirteen patients showed amelioration of left hemineglect in conditions of left-monocular viewing, as compared to the baseline binocular state. Although this result superficially resembles the Sprague effect, two patients benefited from right-monocular viewing whereas eleven patients showed no significant change in either right or left viewing conditions. The possible role of structures mediating interocular differences in target detection in cases of right hemisphere damage is discussed. It is suggested that even if the Sprague effect contributes to the salubrious influence of monocular viewing it is hardly the single factor involved.
Implantation of cultured rat foetal adrenal gland cells reverses amphetamine-induced rotation in the 6-hydroxydopamine-lesioned rat striatum: behavioural, ultrastructural and voltammetric data
Authors: Earl Christopher D. , Kruk Zygmunt L. , Bird Margaret M.
Published: December 2019

Roller tube cultures of foetal rat adrenal gland grown in the presence of nerve growth factor were implanted into the 6-hydroxydopamine-lesioned rat striatum to assess the ability of such cells to release catecholamine and restore function. Fast cyclic voltammetry was used to demonstrate that the lesions significantly reduced dopamine overflow following electrical stimulation of brain slices of the ipsilateral caudate putamen and nucleus accumbens. Viable reaggregates caused a significant reduction in the amphetamine-induced rotational behaviour over a period of 33 days, but no reduction of rotation was observed after the implantation of control materials. Fast cyclic voltammetry within and around the site of the implant was unable to demonstrate electrically stimulated dopamine overflow. Transmission electron microscopy of sections taken from the lesioned and implanted striatum failed to demonstrate any transformation by the implants towards a neuronal phenotype.
Does monocular viewing improve target detection in hemispatial neglect?
Authors: Serfaty C. , Soroker N. , Glicksohn J. , Sepkuti J. , Myslobodsky M.S.
Published: December 2019

Experimental animals with large posterior-cortical lesions develop disturbances of visual perception and visually-guided behavior in the contralateral space, resembling the syndrome of unilateral spatial neglect (USN) in humans. The visuo-motor performance in the ignored space is recovered some time following additional lesion inflicted to the contralesional superior colliculus or section of the intercollicular pathways. Based on the model that explains this recovery by disinhibition of the ipsilesional superior colliculus (the ‘Sprague effect’) Posner and Rafal [37] proposed that ipsilesional monocular occlusion could possibly reduce the ‘tone’ of contralesional collicular neurons thereby removing an important contributor of hemineglect. A group of twenty-six right-hemisphere-damaged patients with USN was given a cancellation task under binocular and monocular (left and right) viewing conditions. Thirteen patients showed amelioration of left hemineglect in conditions of left-monocular viewing, as compared to the baseline binocular state. Although this result superficially resembles the Sprague effect, two patients benefited from right-monocular viewing whereas eleven patients showed no significant change in either right or left viewing conditions. The possible role of structures mediating interocular differences in target detection in cases of right hemisphere damage is discussed. It is suggested that even if the Sprague effect contributes to the salubrious influence of monocular viewing it is hardly the single factor involved.
No evidence for enhancement of recovery from a crush lesion of a motor nerve in rats by Org2766
Authors: Ulenkate Herman J.L.M. , Gispen Willem-Hendrik , Jennekens Frans G.I.
Published: December 2019

The present study was undertaken to investigate the effect of Org2766 on the recovery of lesioned motor nerve fibres. The facial nerve of Wistar rats was crush lesioned and the process of recovery was assessed by functional and histological methods. Functional recovery was examined in two experiments and was assessed by quantifying blind the return of eyelid and whisker movements. No difference could be demonstrated between Org2766-treated and saline-treated groups of animals. The histological investigations involved quantifying the number of reinnervated motor endplates in the whisker muscle. On days 10 to 12 in male rats and on days 12 and 13 in female rats, there was no difference in reinnervation between the two treatment groups. It was concluded that with the methods used in this study, no significant effect of Org2766 on the axonal regeneration of motor nerve fibres could be established.
Stimulation of nerve regeneration by macrophages in granulation tissue
Authors: Dahlin Lars B. , Miyauchi Akira , Thomsen Peter , Danielsen Nils , Kanje Martin
Published: December 2019

The effects of granulation tissue exposure on regeneration of sensory axons after a test crush lesion in rat sciatic nerves were studied. Chromic catgut threads were applied subcutaneously in the back of rats. Three weeks later the surrounding granulation tissue was isolated and transposed to the sciatic or tibial nerve in the same rat. Immunocytochemical, light and electron microscopic evaluation of the isolated granulation tissue revealed numerous EDI and ED2 positive macrophages. After an additional three weeks the sciatic nerves were crushed and the axonal outgrowth lengths were measured by the pinch reflex test and by neurofilament staining 3 or 6 days later. The regeneration distances in the sciatic nerve exposed to granulation tissue were significantly longer compared with that of nerves to which only subcutaneous tissue was transposed. Thus, the nerve had become conditioned by the transposure of macrophage rich tissue. After the transposure macrophages were present close to the nerve at the time point of the test crush lesion, but no signs of degeneration or inflammation in the endoneurial space were observed. It was also found that the outgrowth lengths in the tibial nerve branch were consistently longer than in the peroneal branch of the sciatic nerve. It is concluded that granulation tissue, containing macrophages, can induce a conditioning effect in the sciatic nerve. We suggest that this effect is related to factors emanating from macrophages in the transposed tissue.
Invading and resident macrophages in the regenerating rat vagus nerve in vivo and in vitro
Authors: Magnusson Sofia , Kanje Martin
Published: December 2019

Invading and resident macrophages were studied in the regenerating rat vagus nerve in vivo and in vitro, using antibodies to invading (EDI) and resident (ED2) macrophages. Fresh vagus nerves contained no EDI positive macrophages as revealed by immunocytochemical staining. In crush lesioned nerves in vivo, the number of EDI positive cells around and distal to the crush lesion, increased dramatically with time. Interestingly, EDI positive cells, although few, appeared in the cultured vagus nerves subjected to a crush lesion. Resident ED2 positive macrophages were abundant in fresh nerves. In vivo, there was a small increase of ED2 positive macrophages at the crush area as regeneration proceeded. In contrast, no increase was observed in vitro and after 3 days no ED2 stained macrophages were found. Immunocytochemical staining for low-affinity NGF-receptors showed a dramatic increase at the crush and distal to it in vivo, while in vitro, the receptors were upregulated along the entire nerve. The results suggest that invading macrophages may not be crucial for the initial and early outgrowth of sensory nerve fibres in peripheral nerves.
Intrastriatal grafts of fetal ventral mesencephalic tissue restore quantitative and qualitative D1/D2 dopamine receptor synergism in the striatum
Authors: Johnston Rowena E. , Hu Xiu-Ti , White Francis J. , Becker Jill B.
Published: December 2019

Grafts of fetal ventral mesencephalic (VM) tissue into the striatum of unilaterally 6-hydroxydopamine lesioned rats reduce many of the behavioural and neural changes associated with the lesion. In this report, the ability of such grafts to restore the qualitative and quantitative synergistic relationship between Dl-like and D2-like receptors in the striatum was investigated. In animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal bundle, there was a loss of qualitative and quantitative DA receptor coupling in the striatum, consistent with previous reports. Intrastriatal fetal VM grafts restored both qualitative and quantitative DA receptor synergism to the same level as was observed in the intact striatum. Thus, the ability of intrastriatal grafts to ameliorate some behavioural deficits observed after unilateral lesion may be due to the recoupling of DA D1/D2 synergisms within the striatum.
Non-competitive NMDA antagonists and anti-oxidant drugs reduce striatal atrophy and facilitate recovery of function following lesions of the rat cortex
Authors: Hoane M.R. , Raad C. , Barth T.M.
Published: December 2019

Following brain injury there is an excessive release of glutamate, a reduction in levels of cellular Mg+ +, and the generation of oxygen free radicals. These processes may contribute to the severity of the behavioral impairments seen following brain injury by leading to secondary neuronal degeneration. The present experiment investigates the relative effects of three drugs (MK-801, an NMDA antagonist; magnesium chloride, an NMDA antagonist; and N-tert-butyl-α-phenylnitrone (PBN), an anti-oxidant and free radical scavenger) which disrupt different aspects of the pathophysiological process, in reducing these impairments. Direct comparisons of these drugs may determine if one treatment is more effective than another, or if one is detrimental. In addition, the effects of combination treatments including PBN and MK-801 or MgCl2 were examined. These combination treatment were aimed at the possibility of potentiating the beneficial effects observed after administration of these agents alone. Rats received unilateral electrolytic lesions of the somatic sensorimotor cortex followed by a regimen of MK-801 (1 mg/kg), MgCl2 (1 mmol/kg), PBN (100 mg/kg), MK-801 + PBN (1 mg/kg, 100 mg/kg), MgCl2 + PBN (1 mmol/kg, 100 mg/kg), or saline (1 ml/kg) beginning 15 min following injury. Rats were tested on several sensorimotor tasks (i.e. forelimb placing and foot-fault) for 43 days following the cortical lesions. Rats receiving any of the single or combination drug treatments showed a significant facilitation of recovery on the sensorimotor tasks compared to saline control rats. On one behavioral test (i.e. foot-fault) there was a significant further enhancement of the recovery by combination treatments compared to the single treatment groups. These data are consistent with the idea that excessive release of glutamate, reduction in Mg+ + levels, and free radical generation contribute to the severity of the behavioral impairments following cortical injury, and that arresting these processes results in a facilitation of behavioral recovery. Anatomical analysis showed that all drug treatments decreased the amount of atrophy seen in the ipsilateral striatum.