bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired learning correlates with size of excitotoxic hippocampal	CA3 lesions in adult rats, but shows no amelioration by CA3 transplants
Authors: Aznar Susana , Rasmussen Thøger , Zimmer Jens
Published: December 2024

Hippocampal CA3 pyramidal cells grafted as cell suspensions to excitotoxic hippocampal lesions in adult rats can exchange several types of short and long range nerve connections with the host brain. We now examined whether such grafts also had functional effects in terms of ameliorating lesion-induced learning and memory deficits. Adult, male rats with bilateral, one week old, ibotenic acid-lesions of the hippocampal CA3 region, were grafted with suspensions of fetal (E18-19) CA3 cells. Seven weeks later the animals were tested for spatial navigation in the Morris Watermaze, together with groups of lesion-only and sham-operated, control rats. The tests were performed over 5 days, with 4 trials per day. At the end of the trials, the size of the lesions and the size and structural incorporation of the transplants in the host brains were evaluated morphometrically for correlations with the behavioural data. We found significant differences in swim pathlength and latency to find the platform in the Morris Watermaze between the lesion-only group and the grafted group versus the sham operated group, but no significant difference between the lesion-only and the grafted group. There was a significant positive correlation between the size of the CA3 lesions and the paucity of performance of the rat in the Watermaze, just as spontaneous recovery accordingly had not occurred over the 8 weeks postlesion. We conclude that the behavioural improvement exerted by the CA3 cell suspension grafts, at a time point when graft-host connections have had time to establish, is at most incomplete by these transplants, pointing to the difficulties there may be in obtaining full functional integration.
Abstracts of the International Symposium Excitatory Amino Acids "Ten	Years Later" held in Manaus, Brazil on November 1922, 1998
Authors: Cavalheiro Esper A. , Schoepp Darryle , Turski Lechoslaw
Published: December 2024

The past decade has led to many significant advances in the understanding of the function of excitatory amino acids in synaptic transmission. The cloning of the ionotropic and metabotropic glutamate receptor families has produced new strategies for the pharmacological modulation of glutamate transmission. The engineering of transgenic animals with modified expression of receptor proteins has created new insights into the function, dysfunction and possible pathology causally related to glutamate receptors. Advances in the pharmacology of glutamate receptors has lead to clinical research addressing multiple therapeutic applications of drugs that act on excitatory amino acid systems. A number of NMDA receptor antagonists have now been studied in humans. AMPA/kainate and metabotropic receptor active compounds have left the preclinical realm of research and have moved towards or are in the clinic. Excitatory amino acid research has brought new therapeutic concepts and increased immensely our understanding of how the brain works. The pharmaceutical industry has explored the emerging concepts and therapy related principles in the clinic. Research on excitatory amino acids in the last ten years has produced a foundation for future therapeutic strategies that are highly innovative, and now hold considerable promise to deliver novel pharmaceuticals for both neurological and psychiatric disorders. November 1998, after a long ten year break, marks the second symposium on "Excitatory Amino Acids - Manaus '98". The conference is organized under the auspices of the Brazilian Academy of Sciences, the Federation of Brazilian Societies of Experimental Biology and the Brazilian League Against Epilepsy. The selection of the venue has a symbolic characteristic and addresses the research in South America and developing countries. The meeting addresses today's emerging questions and the new avenues which glutamate research is taking in to the future from the perspectives of molecular biology, physiology, pathology, pharmacology, and medicine. It is our goal that scientists from a variety of disciplines will benefit from the information provided.
Effects of enriched postoperative housing conditions on spatial	memory deficits in rats with selective lesions of either the hippocampus,	subiculum or entorhinal cortex
Authors: Galani R. , Coutureau E. , Kelche C.
Published: December 2024

Long-Evans male, adult rats received selective and bilateral lesions of either the hippocampus, subiculum or lateral entorhinal cortex, and were then housed for 30 days in either enriched or standard conditions. Rats were then tested in the eight-arm radial maze to assess spatial working memory and the strategies that were employed (i.e. pattern of arms visited). Lesions of the hippocampus induced both a working-memory impairment and a loss in the use of allocentric strategies to perform the task. Rats with lesions of the subiculum were also impaired but less than hippocampectomized rats and showed a similar pattern of arm visits as control rats. In contrast with other lesioned rats, rats with lateral entorhinal cortex lesions performed the task like control rats. Postoperative enriched housing conditions (EHC) globally enhanced performance of rats, but did not affect the strategies selected by the rats to solve the task. The beneficial effect of EHC was particularly obvious in rats with lesions of the subiculum. In enriched rats with such lesions, performance was not significantly different from that of control rats housed in standard conditions. The present results indicate that 1) the structures within the hippocampal formation are not similarly involved in spatial learning and memory processes and in the management of navigational demands of the radial maze, and 2) enriched conditions may enhance the spared spatial abilities of some lesioned rats thus promoting functional recovery.
Opposite effects of pinealectomy and melatonin administration on	brain damage following cerebral focal ischemia in rat
Authors: Joo Jin-Yang , Uz Tolga , Manev Hari
Published: December 2024

The endocrine system has been recognized as an important factor that may contribute to the outcome of stroke. We tested in rats the hypothesis that the pineal gland and/or its hormone melatonin may affect the outcome of a transient cerebral arteries occlusion (CerAO). Reversible 90 min focal ischemia was produced using a three-vessel occlusion method. Surgically or sham pinealectomized rats were exposed to CerAO 15 days after surgery. Melatonin (4 x 2.5 mg/kg: 30 min prior to onset of CerAO, immediately after recirculation was established, and 1 and 2 hr later) or its vehicle were administered intraperitoneally. The outcome of CerAO was assessed by quantitative assay of DNA damage or by Nissl staining and measurement of the infarct volume. Pinealectomy increased both the extent of DNA damage and the infarct volume; administration of melatonin to pinealectomized rats reduced both these markers of brain injury. We propose that the pineal endocrine system may influence the outcome of stroke. The mechanism of action and the pathophysiological role of this system, e.g., in aging, should be further characterized.
Differential effects of GDNF treatment on rotational asymmetry,	skilled forelimb use deficits and sensory neglect in unilateral 6-OHDA-lesioned	rats
Authors: Schneider J.S. , Peacock V.
Published: December 2024

The ability of a single intranigral infusion of glial cell line-derived neurotrophic factor (GDNF) to reverse deficits in skilled paw usage and sensorimotor orientation and to ameliorate apomorphine-induced rotational asymmetry in unilateral 6-hydroxydopamine-lesioned rats was examined. After lesioning, all rats developed sensory inattention on the side contralateral to the lesion, rotational asymmetry in response to apomorphine administration and significant deficits in succesfully performing a forelimb reaching task dependent upon the use of somatosensory and proprioceptive feedback. A single intranigral injection of GDNF (300 µg) made 4 wks. after the 6-OHDA lesion, significantly decreased the number of drug-induced rotations at 1 and 2 wks. after GDNF administration. At the same time however, no improvements were noted in perfomance of the paw reaching task or in sensorimotor orienting. Post mortem analyses showed that the GDNF treatment did not cause any increase in striatal dopamine levels but did increase tyrosine hydroxylase-positive immunohistochemical staining in the substantia nigra on the side of the GDNF infusion. These results demonstrate the need for multiple behavioral measures of efficacy when evaluating treatments for parkinsonism in the unilateral 6-hydroxydopamine lesion model in the rat.
Muramyl dipeptide injected into crushed sciatic nerve, activates	macrophages and promotes recovery of walking locomotion in rats
Authors: Fukuyama Ryuichi , Takeda Hiroshi , Fushiki Shinji , Yamamoto Tetsuro
Published: December 2024

We injected an immunoadjuvant, muramyl dipeptide (MDP), intrafascicularly into crushed rat sciatic nerve so as to test whether activation of macrophages promotes regeneration of peripheral nerve from crush injury and improves walking locomotion in rats. Immunohistochemical staining of Schwann cells and macrophages with anti-S100 and ED-1 monoclonal antibodies revealed that macrophages are more abundant and phagocytic in nerve injected with MDP than in control. Axonal elongation in damaged nerve and locomotion recovery in rats were evaluated with pinch test and measurement of sciatic nerve functional index (SFI), respectively. Pinch test showed a 15.5% increase in length (n = 6, p < 0.05) of elongating axons for MDP-injected group 5 days after the crush injury comparing to the control group. The value of SFI obtained from the rats injected with MDP showed a 18.3 % increase (n = 4-6, p < 0.01) comparing to the control 3 weeks after the crush injury. Activation of macrophages in the nerve injected with MDP was monitored by detecting gene expression of marker molecules for macrophages such as apolipoprotein E (ApoE), interleukin-1ß (IL-1ß) and macrophage inflammatory protein-1a (MIP-1a) using reverse transcription-PCR (RT-PCR) technique 2 days and 1 week after the injection. Levels of transeripts of IL-1ß and MIP-1a were up-regulated in the nerves injected with MDP 1 week after MDP injection. These results suggest that an intrafascicular injection of MDP activates macrophages infiltrating into damaged nerve and that the macrophages support elongation of regenerating axon, resulting in functional recovery of sciatic nerve from injury in rats.
Spontaneous and induced recovery of visual hemineglect during	cooling inactivation of middle suprasylvian cortex in the cat
Authors: Geeraerts Sarah , Vandenbussche Erik
Published: December 2024

The purpose of the present study was to observe recovery of orienting deficits during unilateral and bilateral cooling inactivation of the middle suprasylvian (MS) cortex. Unilateral MS cooling resulted in a contralateral hemineglect (no orienting responses towards stimuli in the contracooled hemifield) that spontaneously recovered within less than 40 min of continued cooling. Moreover, the brain changes responsible for this recovery were partially retained and cumulated over successive cooling days. Bilateral MS cooling indicated that recovery of neglect can be induced by a restoration of the imbalance between activity levels of structures in both hemispheres and revealed an interaction between spontaneous and induced recovery of neglect. These results show that considerable changes may occur in the brain during cooling for rather short periods. Possible explanations for these changes are discussed.
Variability of residual vision in hemianopic subjects
Authors: Wessinger C. Mark , Fendrich Robert , Gazzaniga Michael S.
Published: December 2024

Using stabilized visual field mapping techniques, seven hemianopic subjects were extensively investigated for residual visual abilities. Iso-lated islands of detection abilities were demonstrated by four of these subjects. Additional abilities demonstrated within these islands included saccadic and verbal localization, wavelength discrimination, form discrimination, and motion detection. These abilities were also accompanied by low-confidence ratings, and thus have the character of blindsight. It is noteworthy that different subjects demonstrated different abilities at different visual field locations, underscoring the between and within subject variability often observed with blindsight. Furthermore, magnetic resonance images obtained for each subject demonstrated variable sparing of occipital cortex. Such cortical sparing, in conjunction with the behavioral variability, supports the notion that some instances of blindsight are mediated by remnants of the primary visual pathway.
Influence of age-related factors on long-term outcome after	traumatic brain injury (TBI) in children: A review of recent literature and	some preliminary findings
Authors: Benz Barbara , Ritz Annegret , Kiesow Susanne
Published: December 2024

Cerebral plasticity of the immature brain is often inferred to lead to less serious consequences of early traumatic brain injury (TBI) in the pediatric age group. This notion is seriously challenged by recent research findings. Data from prospective studies point to some children's dif-ficulties in ongoing skill-acquisition and the possibility of late-emerging deficits. Accordingly, preliminary group data of an own ongoing study support the notion of an increased risk for pervasive neuropsychological impairment in subjects with severe TBI and early age at trauma. The pattern of neuropsychological deficits may depend on the developmental level at the time of injury, although effects of hemispheric site of lesion were also found to persist in individual cases. Theoretical considerations and empirical findings stress the importance of a longitudinal developmental perspective for the evaluation of long-term outcome after pediatric TBI. ("Verbund Neurotrauma Kiel / Project 4: Evaluation of neurological rehabilitation and course of cognitive development in children and adoles-cents with secondarily acquired brain damage", funded through the Research Program "Gesundheit 2000" of the German government, FKZ 01 KO 9512.)
Protein S-100B and neuron specific enolase as early	neurobiochemical markers of the severity of traumatic brain injury
Authors: Herrmann Manfred , Curio Noreen , Jost Stefan , Wunderlich Michael T. , Synowitz Hans , Wallesch Claus-W.
Published: December 2024

The present study aimed at the predictive value of early release patterns of protein S-100B and neuron specific enolase (NSE) in patients with traumatic brain injury. We investigated 69 patients who were admitted to the Department of Neurosurgery following traumatic brain injury. Both NSE and S-100B serum concentrations during the first three days after admission were highly and significantly correlated with Glasgow Coma and Coma Remission Scale scores at the respective blood sampling times as well as 2 weeks later. Signs of intracranial pathology as evaluated by CCT or MRI scans showed no association with NSE or S-100B release patterns. Our data support the hypothesis that NSE and protein S-100B are useful and sensitive neurobiochemical markers for the early clinical outcome of traumatic brain injury.
Mechanisms underlying the pathogenesis of urinary bladder	instability - new perspectives for the treatment of reflex	incontinence
Authors: Callsen-Cencic Peter , Mense Siegfried
Published: December 2024

The urine storage ability of the urinary bladder is markedly impaired following inflammation of the urinary bladder and spinal cord injury because of a hyperexcitability of micturition reflexes. Using two rat models of inflammation-induced bladder overactivity and detrusor hyper-reflexia following spinal cord injury we investigated changes in the neuronal pathways to the urinary bladder which may underlie the development of this instability. Our results suggest that among the factors involved in inflammation-induced bladder instability are significant changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide and galanin at the primary afferent level, as well as of the enzyme neuronal nitric oxide synthase (nNOS) at the afferent and postganglionic efferent level. In the lumbar and sacral spinal cord nNOS-immunoreactivity was depleted from dorsal horn neurones in both cystitis and spinal cord injured rats and from preganglionic parasympathetic neurones after spinal cord injury. Distension of the bladder in chronically spinalized rats elicited c-Fos expression in a significantly greater number of neurones throughout the lumbar and sacral segments than in rats with an intact neuraxis. Thus, under pathological conditions rather complicated changes in the synthesis of neuropeptides and nNOS occur at the primary afferent, spinal cord and postganglionic efferent level that together control the activity of the urinary bladder. Further mechanisms like unmasking of silent synapses and axonal sprouting in the spinal cord might further contribute to an increase in activity in micturition reflex pathways. Local cooling of the dorsal spinal cord at the level L6/S1 with temperatures between 14 and 20 °C proved a simple technique to control the unstable bladder and restore continence in both inflammation-induced detrusor overactivity and detrusor hyperreflexia following spinal cord injury. The effects of cooling are probably the result of a blockade of synaptic transmission within the dorsal cord which eliminates neuronal overactivity. Thus, local spinal cord cooling could offer a new method to treat bladder instability and reflex incontinence.
The development of visual functions in cerebrally blind children	during a systematic visual field training
Authors: Werth R. , Moehrenschlager M.
Published: December 2024

Sixteen children aged 1 to 15 years who were blind due to an ischemic postgeniculate cerebral lesion after perinatal asphyxia and 6 children aged 1 to 13 years who were blinded after a postgeniculate traumatic cerebral lesion participated in a systematic visual field training. Thirty-one children who were blind due to a postgeniculate lesion following perinatal asphyxia and 12 children who suffered from blindness after a traumatic postgeniculate lesion served as controls. These children received no visual field training or an ineffective visual field training. The extension of the functional visual field and the functional luminance difference threshold were assessed with a specially designed arc perime-ter. In all children blindness had already persisted for at least one year. Visual functions developed within a training period of three months in 15 of 22 children who received visual field training whereas there was no spontaneous recovery in the control group. The functional luminance difference threshold was still elevated above normal in the case of 5 children who recovered from blindness. In 2 children the latency of sac-cades elicited by light targets in the formerly blind visual area was significantly longer than the latency of saccades elicited by targets in the normal area of the visual field. Light scatter was controlled in order to exclude that the widening of the visual field during training which we interpreted as a sign of the development of visual functions was an effect of scattering light. The findings support the assumption that system-atic stimulation of cerebrally blind areas may facilitate the development of visual functions in brain damaged children. The cerebral lesions associated with the impaired visual functions which improved during the treatment are in agreement with the assumption that spared tissue in the striate and extrastriate visual cortex and underlying white matter is the anatomical basis of the shrinkage of the blind areas.
Restorative and compensatory therapy approaches in cerebral	blindness a review
Authors: Kerkhoff Georg
Published: December 2024

In the first part of this review, different types of homonymous Visual Field Disorders (VFDs) and their resulting visual disabilities are ana-lyzed in 313 patients with VFDs and 141 patients without VFDs from a neurorehabilitation centre for adults. Homonymous hemianopia was the most frequent visual field loss (54.7 %), followed by hemiamblyopia (23.3 %), quadrantanopia (15.3 %) and paracentral scotomata (6.7 %). About 70 % of all VFD patients had a visual field sparing of 5° or less (macula or foveal sparing). Patients with VFDs frequently showed two types of disabilities: hemianopic alexia was subjectively reported and objectively found in 5090 % of all patients, and visual exploration deficits in the scotoma were complained and found in 1770 % of the VFD patients. While hemianopic alexia was related to parafoveal visual field sparing, and additionally to visual acuity in patients with bilateral VFDs, visual exploration deficits were correlated to the size of the area in the scotoma in which the patient searched for a stimulus with saccadic eye movements (search field). The size of the search field in the intact hemifield was not related to visual exploration deficits in unilateral VFDs. As a third disability, visual-spatial deficits in VFD patients are summarized. In the second part, restorative and compensatory treatment approaches for postchiasmatic VFDs are reviewed. Partial restitution of blind regions in the visual field is achieved in the majority of patients treated with purely restorative methods including saccadic localization or light detection in the scotoma. However, the amount of the visual field recovered is limited to 512° (mean) in 90 % of these patients. Compensatory treatments seek to improve the substitution of the lost field region by large-scale saccadic eye move-ments to the scotoma, spatially organized search strategies in both visual hemifields, and by training small-scale eye movements required for reading. Significant improvements in these areas are achieved in 95 % of all VFD patients with these treatment techniques, with documented transfer to visually related activities of daily living. Furthermore, a significant though limited visual field increase of 57° is achieved in 30 50 % of patients treated in this way. In the final section, promising approaches that might lead to new treatment techniques for VFDs are reviewed. Among these are the gaze-dependant modulation of scotomata, training-dependant enlargement of the useful field of view, a nd t he uncovering of residual visuomotor capacities to visual stimuli in a scotoma.
Amantadine improves water maze performance without affecting motor	behavior following traumatic brain injury in rats
Authors: Dixon C. Edward , Kraus Marilyn F. , Kline Anthony E. , Ma Xiecheng , Yan Hong Q. , Griffith Raymond G. , Wolfson Brian M. , Marion Donald W.
Published: December 2024

Amantadine, a dopamine agonist, is reported to have beneficial effects on the neurobehavioral sequelae of clinical brain injury. However, there are currently no published laboratory reports on its use in the assessment of functional or histopathological outcome following experimental traumatic brain injury (TBI). To this end, we examined the effects of daily amantadine treatment on functional recovery (motor and Morris water maze performance) and hippocampal neuronal survival following controlled cortical impact (CCI) injury (4 meters/sec, 2.7 mm tissue deformation). Male Sprague-Dawley rats were pretrained on motor performance tasks (beam balance and beam walking) one day prior to injury and tested on post-operative days 15. Additionally, all subjects were trained on the Morris water maze on post-operative days 1418. Beginning one day after CCI injury or sham surgery, animals were injected once daily for 18 days with either amantadine (10 mg/kg, i.p.) or saline. The amantadine treatment regimen was ineffective in promoting motor recovery and increasing survival of hippocampal neurons in both the CA1 and CA3 regions following TBI, but did show improved swim latencies during the five days of water maze testing (Day 14 vs. Day 18, p < 0.01) when compared to saline controls. Mean (± SE) swim latencies on Day 18 were 15.12 ± 2.8, 13.25 ± 4.18, 70.83 ± 11.1, and 38.5 ± 3.55 sec for the sham/saline, sham/amantadine, injured/saline, and injured/amantadine treatment groups, respectively. Thus, while the daily administration of amantadine exhibited a neutral effect on motor behavior, it produced a modest attenuation of water maze performance deficits. This latter finding is consistent with published clinical data suggesting a beneficial effect on functional outcome with amantadine therapy.
Scar modulation in subacute and chronic CNS lesions: Effects on	axonal regeneration
Authors: Stichel Christine C. , Lausberg Friederike , Hermanns Susanne , Müller Hans Werner
Published: December 2024

After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons. Adult rats underwent unilateral transection of the postcommissural fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods. A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration. These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries.
Long term evaluation of experimental median nerve repair by frozen	and fresh nerve autografts, allografts and allografts repopulated by autologous	Schwann cells
Authors: Accioli-de-Vaconcellos Zulmar Antônio , Kassar-Duchossoy Lina , Mira Jean-Claude
Published: December 2024

The authors used different kinds of peripheral nerve grafts to reconstruct a terminal branch of the brachial plexus (the median nerve) gap of adult Sprague-Dawley rats, including fresh or frozen autografts and allografts from Norway rats. They also performed acellular allograft repopulation by autogenous Schwann cells, to improve the environment for nerve regeneration. Three, six, nine and twelve months after grafting, rats underwent histological assessment (muscle, nerve and spinal cord) and simple functional assessment by the grasping test. Initially, the functional recovery of frozen grafts was lower than fresh graft recovery, but twelve months after surgery it was similar for both types of graft.
Age but not sex affects motor recovery after unilateral	sensorimotor cortex suction-ablation in the rat
Authors: Goldstein Larry B. , Bullman Sarah
Published: December 2024

Both age and sex can influence recovery after brain injury. To determine the impact of these variables on motor recovery, young (2 month old) and older (5-6 months old) male and female rats were first trained to traverse a narrow elevated beam. Rats then underwent suction-ablation of right sensorimotor cortex or sham operation. Motor recovery was measured by repeated testing on the beam over 3 weeks. Shamoperated rats performed perfectly regardless of age or sex throughout testing. There was no difference in beam-walking scores among the groups of lesioned rats on the first trial 24 hrs. after injury (Kruskal-Wallis H = 0.18, p = 0.98). There was a significant effect of age (two-way ANOVA F1,32 = 29.58, p < 0.0001) but not sex (ANOVA F1,32 = 0.78, p = 0.38) on subsequent recovery. These data show that motor recovery after unilateral injury to the sensorimotor cortex varies with age, but not sex.
Homotopic septal grafts combined with a hydrogel bridge promote	functional recovery in rats with fimbria-fornix lesions: A unit recording	study
Authors: Duconseille Elee , Cressant Arnaud , Kelche Christian , Woerly Stéphane , Will Bruno , Poucet Bruno , Cassel Jean-Christophe
Published: December 2024

Fimbria-fornix lesions abolish the hippocampal electrophysiological activity time-locked to the theta rhythm and alter some functional characteristics of place cells. The present experiment investigated whether homotopic grafts of fetal septal cells can alleviate some of these alter-ations when combined with a polymeric hydrogel bridging a fimbria-fornix lesion-cavity. Eleven months after grafting surgery, unit recordings were obtained from hippocampal neurons of seven rats [two sham-operated (S), two lesion-only (L) and three grafted (G)] while they explored a radial maze. The lesions induced dramatic loss of hippocampal acetylcholinesterase(AChE)-positive reaction products. Surviving grafts were found in the three grafted rats and several AChE-positive processes could be observed in the polymeric hydrogel, as well as in the most dorsal portion of the hippocampal parenchyma. Of 168 recorded units, 132 were hippocampal interneurons (i.e., fired rapidly everywhere in the maze), and 36 were pyramidal place cells (i.e., fired only when the rat was in a specific location in the maze, the place field). The overall firing characteristics of either cell type were similar in S, L and G rats. However, while none of the interneurons recorded from L rats was found to fire rhythmically, a significant proportion of interneurons recorded from S and G rats had an activity pattern time-locked to the theta rhythm [S: 16/19 (84 %); G : 22/70 (31 %)]. In addition, the increase in firing activity observed in interneurons recorded from S rats when they were moving was disrupted in cells from L rats, but partially restored in cells from G rats. Concerning place cells, most (93 %) place fields in S rats were stable relative to extra-maze cues when the radial maze was rotated, while they followed the maze rotation in both L and G rats. Because of the low number of rats used, the present results should be considered with caution. Nevertheless, they indicate graft-induced recovery of some properties of hippocampal function following fimbria-fornix damage, and suggest that homotopic transplants of projection neurons may foster some func-tional recovery when provided with a biomaterial allowing the host or grafted neurons to cross the lesion cavity.
Decreased Cyclosporin A requirement with anti-ICAM-1 and	anti-LFA-1 in a peripheral nerve allotransplantation model
Authors: Fox Douglas J. , Doolabh Vaishali B. , Mackinnon Susan E. , Genden Eric M. , Hunter Daniel A.
Published: December 2024

Object: This study evaluated the dose related effects of Cyclosporin A (CsA) alone and in combination with monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1) and the alpha subunit of leukocyte function-associated antigen (LFA-1 ) on peripheral nerve allograft rejection in a rat model. Methods: Nerve regeneration was assessed using gait analysis of returning hind limb function, histology, and morphometry. Results: Regeneration comparable to isograft controls and high dose CsA treatment groups was observed when mAbs were used in combi-nation with intermediate dose CsA. Intermediate dose CsA therapy without additional mAbs was insufficient to support this level of regeneration. Nerve allografts treated with high and low dose CsA demonstrated no increased benefit with the addition of mAb therapy. Conclusions: Thus, mAbs seem to have a dose dependent effect on immunosuppression when used in combination with CsA, and may have therapeutic promise as a rescue therapy when CsA levels fall or issues of toxicity become important.
Anatomical but not functional recovery from a sciatic nerve crush	is enhanced by treatment with testosterone
Authors: Swallow Richard K. , Leiser Matthew R. , Fink Bryan E. , Sauer Christa , Nicklous Danielle M. , Hoffman John R.
Published: December 2024

Purpose: Until recently, there has been a limited amount of research comparing functional and anatomical recovery following nerve injury. Previous studies emphasizing anatomical recovery (such as axonal number) have shown that testosterone promotes regeneration in crushed and transected nerves. The purpose of this study was to assess the effect of testosterone on the functional recovery of the sciatic nerve follow-ing a unilateral crush injury. Methods: Young adult male Sprague-Dawley rats were injected daily with either 500 µg testosterone proprionate or vehicle alone. The recovery course was followed for six weeks using functional and behavioral testing. Behavioral tests included a footprint gait analysis (as a measure of motor function), response to a skin pinch, and warm water withdrawal (measures of sensory function). Results: Immediately following surgery, all tests indicated complete denervation to the leg distal to the crush site. Anatomical analysis revealed a 22 % increase in the number of axons in testosterone treated animals at 6 weeks post-crush, but no indication of differences in functional recovery. The results of behavioral testing indicated only minor differences in functional recovery as a result of testosterone treatment. Conclusion: The results indicate the need for a detailed comparison between anatomical regeneration and functional recovery. An increase in axon number alone may not be an accurate indicator of successful regeneration.
Lubeluzole treatment does not attenuate neurobehavioral	dysfunction or CA3 hippocampal neuronal loss following traumatic brain injury	in rats
Authors: ODell Dianne M. , Muir Judith K. , Zhang Chen , Bareyre Florence M. , Saatman Kathryn E. , Raghupathi Ramesh , Welsh Frank , McIntosh Tracy K.
Published: December 2024

Purpose: One of the downstream consequences of glutamate-induced NMDA (N-methyl-D-aspartate) receptor activation following trau-matic brain injury (TBI) is production of nitric oxide (NO). In this study, we evaluated the ability of lubeluzole, a novel neuroprotective com-pound which downregulates the glutamate-activated nitric oxide pathway and blocks sodium and voltage-sensitive calcium channels, to improve behavioral and histological outcome in rats following TBI. Methods: Rats were anesthetized and subjected to moderate lateral fluid percussion brain injury (2.42.6 atm) or were surgically prepared but not injured (sham). Fifteen minutes after injury, animals received a bolus of either vehicle (n = 12 injured, n = 14 uninjured) or lubeluzole (0.31 mg/kg, n = 12 injured, n = 8 uninjured) through the jugular vein followed by a one hour infusion of vehicle or lubeluzole (0.31 mg/kg). Animals were tested at 48 hours post-injury for cognitive performance in the Morris water maze, neuromotor function, and limb placing func-tion, and then sacrificed. Results: While brain injury resulted in significant cognitive and motor deficits, injured animals treated with lubeluzole did not differ in spa-tial memory performance, neuromotor score, or limb placing function from injured, vehicle-treated animals. Furthermore, there was no differ-ence in the mean number of ipsilateral hippocampal CA3 neurons between injured rats treated with vehicle and those treated with lubeluzole. Conclusions: This single-dose study failed to demonstrate a beneficial effect of lubeluzole on the acute behavioral or histological sequelae following TBI.
Amygdalar tissue transplants improve recovery of nociceptive	behaviour in rats
Authors: Jain S. , Mathur R. , Sharma R. , Nayar U.
Published: December 2024

Purpose: Amygdala plays a very important role in the mediation of emotional and affective components of pain. Bilateral amygdalectomy increases the threshold for vocalization, a measure of emotional reactivity, without any change in the tail flick latency. The present work was designed to study the recovery of emotional nociceptive behaviour following neural tissue transplantation in lesioned rats. Methods: In a group of adult wistar rats lesions of the central nucleus of amygdala (CeA) were produced electrolytically. In a separate group of rats amygdalar tissue was transplanted at the lesioned site 2 days thereafter. The vocalization tests, viz. simple vocalization (SV) and vocalization after discharge (VA), which were used to study the emotional nociceptive behaviour were carried out both before and after pro-ducing lesion/transplant. Results: Bilateral CeA lesions increased the thresholds for SV and VA significantly (p < 0.001), indicating analgesia. Following amygdalar tissue transplantation a significant decrease (p < 0.05) in the thresholds were observed when compared with the lesioned group, although when compared with the basal data it showed an increase (p<0.05). Conclusions: The results indicate a partial recovery of the vocalization response following amygdalar tissue transplantation.
Axonal regeneration of mouse retinal ganglion cells by peripheral	nerve transplantation; a quantitative study
Authors: Inoue Tetsu , Sasaki Hitoshi , Hosokawa Mizuho , Fukuda Yutaka
Published: December 2024

Purpose: Retinal ganglion cells (RGCs) of adult mammals can regenerate their axons along a segment of the peripheral nerve (PN) that is transplanted to the cut optic nerve. There have been many trials of PN transplantation to induce axonal regeneration of RGCs in adult rodents, cats and ferrets. However, because of the technical difficulty in transplant operation, PN transplantation in adult mice has not been carried out in spite of the availability of many kinds of gene-manipulated animals. Here we report the procedures for successful PN transplantation in this species. Methods: We made intraretinal (IR) and retrobulbar (RB) approaches for PN transplantation. Four weeks after PN transplantation, RGCs with regenerated axons were identified by retrograde labeling with rhodamine or horseradish peroxidase applied into the PN segment. Results: A quantitative survey showed that the mean regeneration ratio was 1.0 % (n = 8) in IR transplantation, whereas it was only 0.1 % in RB transplantation (n = 11). As previously shown in other species, the regenerated RGCs were predominantly larger-bodied cells in com-parison to intact cells. Conclusion: Possible reasons for the difference in regeneration ratio between the two transplant approaches and the feature of soma size of regenerated RGCs are discussed.
Effects-of fluoxetine on sensorimotor and spatial learning	deficits following focal cerebral ischemia in rats
Authors: Jolkkonen Jukka , Puurunen Kirsi , Rantakömi Sanna , Sirviö Jouni , Haapalinna Antti , Sivenius Juhani
Published: December 2024

Purpose: The present study investigated the effects of fluoxetine, a serotonin reuptake blocker, on behavioral deficits of rats subjected to transient focal cerebral ischemia. Methods: The right middle cerebral artery of rats was occluded for 120 min using the intraluminal filament method. Fluoxetine treatment (5 mg/kg, i.p.) was started 2 days after ischemia induction and treatment was continued for 10 days thereafter. Sensorimotor recovery was assessed using the limb-placing test and cognitive impairment was assessed using a water-maze test at the end of the experiment. Results: Fluoxetine treatment did not improve performance of ischemic rats in the limb-placing test. Nor was the ischemia-induced deficit in the water-maze test affected by fluoxetine. The infarct volumes in the cortex or striatum, determined after the experiment, were not different between ischemic groups. Conclusion: These results suggest that subchronic fluoxetine treatment following experimental focal cerebral ischemia is not detrimental to behavioral outcome, but it also does not enhance spontaneous sensorimotor recovery or attenuate spatial learning deficits.
Methylprednisolone exacerbates axonal loss following optic nerve	trauma in rats
Authors: Steinsapir Kenneth D. , Goldberg Robert A. , Sinha Shini , Hovda David A.
Published: December 2024

Purpose: This study investigates the clinical dogma that very high doses of methylprodnisolone helpful in spinal cord injury are also helpful in optic nerve trauma. Methods: The right optic nerve of 29 male rats received a 5 second traumatic crush followed 30 minutes later by one of five intravenous treatments (methylprednisolone 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, or saline). Treatment was continued for three additional administrations at 6 hour intervals. Untreated sham controls (n = 7) were also prepared. Six weeks after injury, animals were sacrificed, perfused and optic nerves systematically counted. Results: Axon counts (means ± s.e.m.) were as follows: Saline = 16,670 ± 8,900 (n = 5); Methylprednisolone: 30 mg/kg = 8,098 ± 4,741 (n = 5); 60 mg/kg = 6,925 ± 6,517 (n = 4); 90 mg/kg = 2,663 ± 2,653 (n = 4); 120 mg/kg = 6,149 ± 3,487 (n = 6). Consequently, the data revealed that saline treated animals retained more axons than those that were administered methylprednisolone (p < 0.02). Conclusions: We conclude that methylprednisolone exacerbates axonal loss following crush injury in the rat optic nerve. Based on the results of this study, clinical studies of traumatic optic neuropathy in the future should also examine the possibility that corticosteroid treatment may have an adverse effect on visual outcome following optic nerve trauma.
Axonal outgrowth in muscle grafts made acellular by chemical	extraction
Authors: Arai Takeru , Kanje Martin , Lundborg Göran , Sondell Mariann , Liu Xiao-Lin , Dahlin Lars B.
Published: December 2024

Purpose: To compare nerve regeneration in autologous detergent extracted and freeze-thawed muscle grafts and to electrophoretically characterize the grafts. Methods: Autologous acellular muscie grafts were created either by freeze/thawing or by detergent extraction and then used to bridge a 10 mm gap in rat sciatic nerve. The autologous grafts were compared with respect to protein content, using electrophoresis preimplantation, and axonal outgrowth, Schwann cell and macrophage content, using immunocytochemistry (neurofilaments, S-100 protein, ED 1 macrophages) at 520 days postimplantation. Results: The extracted muscle grafts were elastic, but the amount of several proteins was reduced and laminin was still present at a position of basal laminae of the muscle fibers. The freeze/thawed grafts were brittle and lacked elasticity, but resulted in minor changes in major proteins. The axons regenerated through both types of grafts (initial delay 6 days and rate 0.7-0.8 mm/day), which shrunk in length by 25%. There were no apparent differences with respect to Schwann cells and macrophages. Conclusions: The results suggest that detergent extracted muscle tissue, in which some basal lamina proteins remain but cells are removed, could present a new favourable option for nerve grafting.
Quality of Life after Multiple Trauma. Aim and Scope of the	Conference
Authors: Neugebauer E. , Lefering R. , Bouillon B. , Bullinger M. , Wood-Dauphinee S.
Published: December 2024

From September 29 until October 2, 1999, a group of international experts met in Wermelskirchen, Germany, for a consensus conference on "Quality of Life after Multiple Trauma". The meeting was initiated and sponsored by the German Ministry of Education and Research. It was the aim of the group to develop evidence-based guidelines for the systematic evaluation and application of Quality of Life (QoL) measures in patients with severe trauma. The present paper describes the format of the meeting, the selection of the participants, the time schedule, and the proceeding, in order to facilitate the interpretation of the results.

The work was structured according to the different types of injury: traumatic brain injury (TBI), multiple injuries without TBI, spinal cord injury, and children with TBI. For each injury group, a specific task force group with 9--13 members was established, consisting of methodologists as well as clinicians from different disciplines.

The conference was organised as an altenate sequence of plenary sessions and small working group meetings. The work itself was structured according to the following five questions which have been agreed on and distributed to the participants in advance: 1. What is the major problem (ranking) of the patient at different time points after the accident? 2. Which domains of QoL are affected in the sequelae of trauma? 3. Which instruments are useful to evaluate QoL in trauma patients? 4. Which studies have assessed QoL aspects with which instruments? 5. What instruments should be used in which patient group at what time?

The moderators of each task force group summarised the respective results and tried to give recommendations for future application of QoL assessment in trauma patients. As far as possible, the statements should be based on the existing evidence. Furthermore, the groups should recommend QoL measures for use across different patient groups and time points.
Assessing health related quality of life in medicine. An overview	over concepts, methods and applications in international research
Authors: Bullinger Monika
Published: December 2024

Health-related quality of life is increasingly accepted as relevant endpoint in medicine. Available work pertains to development and psychometric testing of measurement instruments. Theoretical papers are largely missing, inclusion of instruments in clinical trials, however, has begun now, especially in oncology and cardiology. Based on a review of the available literature, areas of application of quality of life research are described. Focus of attention are conceptual, methodological and practical challenges as well as the contribution of quality of life research to evaluating the results of medical treatment.
Results of the NIH consensus conference on "Rehabilitation of	Persons with Traumatic Brain Injury"
Authors: Ragnarsson Kristjan T.
Published: December 2024

In 1998, the National Institute for Health (NIH) organized a consensus conference about the rehabilitation of persons with traumatic brain injury (TBI). The conference results are based on an extensive bibliography from the scientific literature and presentations at the conference. The focus of this conference was the evaluation of rehabilitative measures for the cognitive and behavioral consequences of TBI, and the extent to which specific interventions are supported by existing evidence. Specifically, the conference considered the following aspects and their implications for rehabilitation

-- the epidemiology of TBI in the United States,

-- the consequences in terms of pathophysiology, impairments, functional limitations, disabilities, societal limitations, and economic impact,

-- the mechanisms underlying functional recovery following TBI,

-- the common therapeutic interventions for the cognitive and behavioral sequelae of TBI, and

-- the models for comprehensive coordinated multi-disciplinary rehabilitation.

Based on the answers to these questions, the conference tried to give recommendations regarding rehabilitation practices for people with TBI, and identified areas where further research is needed.