bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogens with an Intact Phenolic Group Prevent Death of Neuronal	Cells Following Glutathione Depletion
Authors: Behl Christian , Lezoualc'h Frank
Published: December 2024

Oxidative stress-induced neurodegeneration has been implicated in a variety of neuropsychiatric disorders including Alzheimer's disease (AD). Therefore, neuroprotection is of central interest in basic and preclinical neuroscience. Recently, we reported that the AD-associated amyliod B protein can induce neuronal cell death via the generation of free radicals, oxidative stress and lipid peroxidation. The depletion of the intracellular pool of glutathione (GSH), an important intracellular oxidant, can also induce oxidative events. Various lipophilic antioxidants, including the female sex hormone estrogen, can protect neurons against oxidative cell death. Here, we report that estrogens prevent oxidative cell death induced by GSH depletion in murine clonal hippocampal HT22 cells and in cells of the sympathetic precursor-like cell line PC12. Estrogens act as free radical scavengers and inhibit the intracellular accumulation of peroxides caused by GSH depletion and, ultimately, prevent neuronal cell death. This protective activity is independent of the presence or activation of estrogen receptors but is dependent on the presence of an intact hydroxyl group in the steroid ring A of the estrogen molecule. The modification or the absence of this group led to a loss of the neuroprotective activity. These data further support the important role of antioxidants in neuroprotection and may help in the design of novel antioxidant drugs.
Melatonin: From the Hormone to the Drug?
Authors: Claustrat Bruno , Brun Jocelyne , Geoffriau Martine , Chazot Guy
Published: December 2024

Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland. It is synthesized at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained by the light/dark cycle. Light is able to both suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone is determined by repeated measurement of plasma of saliva MLT or urine sulfatoxymelatonin, the main hepatic metabolite. Melatonin can be considered as the output (the hand) of the endogenous clock. Since the regulating system follows central and sympathetic nervous pathways, an abnormality at any level unspecifically modifies the melatonin secretion, especially in patients with sympathalgia or dysautonomia. Melatonin plays the role of an endogenous zeitgeber on sleep-wake cycle or core temperature. Exogenous melatonin is able to influence the endogenous secretion of the hormone according to a phase response curve. There are therapeutic implications for this property in situations when biological rhythms are disturbed (jet-lag syndrome, delayed sleep phase syndrome, insomnia in blind or elderly people, shift-work). Improvement of pharmaceutical forms studied in controlled trials under the responsibility of the medical community or development of melatonin analogs could lead to decisive progress in this field.
Glumate Receptor Dysfunction and Alzheimer's Disease
Authors: Olney John W. , Wozniak David F. , Farber Nuri B.
Published: December 2024

In this article we review the hypothesis that impaired function of the N-methyl-Daspartate (NMDA) glutamate receptor system may be an important mechanism for understanding the pathophysiology of Alzheimer's disease (AD). We propose a two stage process, the first involving amyloidopathy, oxidative stress and/or energy metabolic disturbances promoting neuronal sensitivity to glutamate-induced excitotoxic injury to an extent that even normal amounts of Glu become excitotoxic. As a consequence, NMDA receptor-bearing neurons (and their NMDA receptors) are deleted from critical corticolimbic brain circuits, which leaves these circuits in an NMDA receptor hypofunctional (NRHypo) state. In the second stage this NRHypo state results in the disinhibition of a complicated neural circuitry that leads to widespread neurodegeneration in corticolimbic areas, consquent neurofibrillary tangle formation and cognitive decline. We propose that certain pharmacological methodes which have been found to protect against NRHypo-induced neurodegeneration in animal brain might be useful treatments for AD.
Indefinite survival of peripheral nerve allografts after temporary	Cyclosporine A immunosuppression
Authors: Atchabahian Arthur , Doolabh Vaishali B. , Mackinnon Susan E. , Yu Samuel , Hunter Daniel A. , Flye M. Wayne
Published: December 2024

It is hypothesized that unlike solid organ transplants immunosuppression of peripheral nerve allografts is needed only for the finite time period required for regeneration of proximal host nerve axons through the allograft and subsequent re-establishment of host end-organ connections. The aim of this study was to explore the consequences of temporary and continuous systemic Cyclosporine A (CsA) immunosuppression upon peripheral nerve allograft survival. Buffalo rats received Lewis nerve allografts under CsA immunosuppression (5 mg/kg/day) either continuously for 20 weeks, or for only 10 weeks followed by abrupt withdrawal. At 20 weeks, the nerve segments from both groups were regrafted into naïve Buffalo or Lewis recipients without further immunosuppression. These grafts were compared with isografts, unimmuno-suppressed allografts and allografts immunosuppressed for 10 weeks in situ. By eight weeks following regrafting, the secondary Lewis recipients had rejected the temporarily immunosuppressed allografts and accepted the continuously immunosuppressed allograft, while the secondary Buffalo recipients accepted both the temporarily and continuously immunosuppressed allografts as assessed by histology and morphometry. Functional recovery was earlier in secondary recipient strain animals that received temporarily immunosuppressed allografts in comparison to those that received continuously immunosuppressed allografts. Analysis of secondary recipients of temporarily immunosuppressed allografts demonstrated greater in vitro MLR and LDA reactivity than did those receiving continuously immunosuppressed allografts. These findings support the hypothesis that donor alloantigens are lost or replaced by the recipient after immunosuppression withdrawal. Moreover, the change to recipient antigenicity in the nerve allograft is retarded and incomplete under continuous CsA immunosuppression, resulting in acceptance by both secondary donor and recipient strains upon regraftment.
2,3-Benzodiazepine AMPA Antagonists
Authors: Tarnawa István , Vize E. Sylvester
Published: December 2024

The 2,3-benzodiazepine GYKI 52466 (1-(4-aminophenyl)-4 methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine) and its analogues represent a family of selective AMPA antagonists. They modulate AMPA channel functions through an allosteric site on the receptor, which is probably different from the ones involved in the actions of cyclothiazide and aniracetam. These compounds are frequently used as research tools to elucidate glutamate receptor-mediated functions. The most effective members of the family inhibit AMPA-induced currents in the submicromolar range. In addition, they are active at low systemic doses in various in vivo experimental models and also possess a good oral bioavailability. In vitro and in vivo pharmacological results with 2,3-benzodiazepine AMPA antagonists indicate their potential therapeutical value in treating a great variety of central nervous system diseases, of which epilepsy and neurodegenerative disorders are regarded as the most important.
End-Organ reinnervation does not prevent axonal degeneration in	nerve allografts following immunosuppression withdrawal
Authors: Midha Rajiv , Munro Cathrine A. , Ang Lee C.
Published: December 2024

Previous work indicated that appropriate end-organ reinnervation fails to influence axonal degeneration in nerve allografts following immunosuppression withdrawal. In the present study, we examined if differences existed in axonal degeneration when axons regenerated across nerve allografts are allowed or completely denied end-organ reinnervation. Two ACI rat nerve allografts (3 cm long) were sutured into gaps created in both peroneal nerves in Lewis rats. In the right leg, the distal end of the graft was connected to the distal host nerve stump to allow end-organ reinnervation. In the left leg, the distal end was turned back and double ligated (unconnected) to prevent end-organ reinnervation. Rats received Cyclosporin A daily for 12 weeks to allow for regeneration and were sacrificed at 16 (n = 5) or 18 (n = 5) weeks following engraftment to assess axonal degeneration following immunosuppression withdrawal. Five Lewis rats receiving autografts served as control and were sacrificed at 12 weeks. Morphometric analysis was performed. In the control group (autografts) the cross-sectional area of and the number of myelinated fibres in the unconnected grafts was double that of the connected grafts, suggesting a sprouting effect. There was a tenfold reduction in the mean number of fibres at weeks 16 and 18 in the allografts compared to controls, without any significant differences in the connected versus unconnected sides. End-organ reinnervation decreases sprouting of axons within the graft but does not protect axons from degeneration following immunosuppression withdrawal.
Sacral electrical neuromodulation as an alternative treatment	option for lower urinary tract dysfunction
Authors: Grünewald Volker , Höfner Klaus , Thon Walter F. , Kuczyk Markus A. , Jonas Udo
Published: December 2024

Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.
Motor rehabilitation after traumatic brain injury and stroke -	Advances in assessment and therapy
Authors: Platz Thomas , Hesse S. , Mauritz K.-H.
Published: December 2024

A long-term goal in motor rehabilitation is that treatment is not selected on the basis of 'schools of thought', but rather, based on knowledge about efficacy and effectiveness of specific interventions for specific situations (e.g. functional syndromes). Motor dysfunction after stroke or TBI can be caused by many different functional syndromes such as paresis, ataxia, deafferentaion, visuo-perceptual deficits, or apraxia. Examples are provided showing that theory-based analysis of motor behavior makes it possible to describe 'syndrome-specific motor deficits'. Its potential implications for motor rehabilitation are that our understanding of altered motor behavior as well as specific therapeutic approaches might be promoted. A methodological prerequisite for clinical trials in rehabilitation is knowledge about test properties of assessment tools in follow-up situations such as test-retest reliability and responsiveness to change. Test-retest reliability assesses whether a test can produce stable measures with test repetition, while sensitivity to change reflects whether a test detects changes that occur over time. Exemplifying these considerations, a reliability and validity study of a kinematic arm movement analysis is summarized. In terms of new therapeutic developments, two examples of clinical therapeutic studies are provided assessing the efficacy of specific inter-ventions for specific situations in arm and gait rehabilitation: the Arm Ability Training for high functioning hemiparetic stroke and TBI patients, and the treadmill training for non-ambulatory hemiparetic patients. In addition, a new technical development, a machine-controlled gait trainer ist introduced.
An Early Onset Rehabilitation Program for Children and Adolescents	after Traumatic Brain Injury (TBI): Methods and First Results
Authors: Melchers Peter , Maluck Andreas , Suhr Lydia , Scholten Stefan , Lehmkuhl Gerd
Published: December 2024

Survived traumatic brain injuries (TBI) are one of the most serious challenges to the patient's future life. Recent literature increasingly questions the long believed protective effects of functional cerebral plasticity in children. Although TBI in children and adolescents is frequent, they are less frequently admitted to rehabilitation centers as in-patients than adults. This emphasizes the role of out-patient treatment. The progressing study described here aims to achieve a contribution to a comprehensive approach in TBI-rehabilitation for youngsters. A two-stage multimethodal program, starting with stimulation in coma while the patient is on the intensive care unit, and neuropsychological therapy after regaining consciousness is to be evaluated in a controlled, prospective and randomized study. After including nearly 50 % of the planned sample (100 persons), some preliminary results can be mentioned with all applicable caution. The effectiveness of the applied therapy can be stated here with respect to the posttraumatic development of intellectual abilities in the 6- and 12 months follow ups. Moreover, in the control group development of psychopathological alterations was found to a considerable degree and also lower ratings in a quality of life questionnaire, compared to the experimental group. It is expected to prove these differences statistically, after the total sample has been included, and thus equal distributions have been achieved in all predictive variables.
Sacral anterior root stimulation and posterior rhizotomy in	spastic neuropathic bladder
Authors: Schumacher Stefan , Bross Stephan , Scheepe Jeroen R. , Alken Peter , Jünemann Klaus-Peter
Published: December 2024

The combination of sacral anterior root stimulation (SARS) and posterior rhizotomy is a successful procedure for the restoration of bladder function after supraconal spinal cord injury. Today, complete posterior rhizotomy has become part of the standard therapy. Conventional SARS leads to simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation-induced detrusor-sphincter-dyssynergia and to achieve physiological voiding. Selective detrusor activation improves current sacral neurostimulation of the bladder, including the poststimulus voiding principle. Selec-tive neurostimulation is possible in the following techniques: anodal block, high-frequency block, depolarizing prepulses, sinusoidal pulses and cryoblock. The anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphinc-ter-dyssynergia and thus improve stimulation-induced voiding. Our experience has shown that future modern selective bladder neurostimulation systems will be based on either the anodal block technique or the cryotechnique.
Quality of Life after traumatic brain injury: A systematic review	of the literature
Authors: Berger Eva , Leven Friederike , Pirente Nicola , Bouillon Bertil , Neugebauer Edmund
Published: December 2024

In modern industrial countries traumatic brain injury (TBI) is a common sequel after different kinds of accidents especially amongst young male adults. Apart from medical and economic consequences Quality of Life (QoL) after TBI becomes increasingly important in outcome assessment. Besides the classical domains of QoL (physical, psychological, social) cognitive impairments are playing an important role especially for TBI patients. In 1991 the Meran conference set important standards and formulated basic guidelines for defining and measuring QoL in surgery, but a special index for TBI patients has not yet been developed. Instead, QoL research concentrates on physical, medical, psychological and social problems only. Based on the existing QoL concept extended by the cognitive aspect it was the aim of this review to give an overview about the recent QoL research in TBI patients since 1991. Sixteen studies in TBI patients mentioning at least 2 domains of QoL (physical, psychological, social, cognitive) were published since 1991. Five of them considered all 4 domains of QoL. All studies except of one dealt with psychological and social problems. Only half of the studies considered cognitive impairments. Four studies tried to define QoL, but none of them included the cognitive component. There was no consensus regarding the definition and the choice of measurement instrument for QoL after TBI. This review of 16 studies considering outcome and QoL after TBI confirms that a homogenous and clinically relevant QoL concept for this group of patients is still missing. Further research in TBI patients should include all 4 domains of QoL.
The incidence and outcome of severe brain trauma Design and	first results of an epidemiological study in an urban area
Authors: Bouillon Bertil , Raum Markus , Fach Hagen , Buchheister Bettina , Lefering Rolf , Menzel Jürgen , Klug Norfried
Published: December 2024

Epidemiological data on the incidence, the prehospital and hospital care and the outcome of traumatic brain injury in Germany are scarce. It is therefore difficult to estimate the importance of this injury with respect to magnitude as well as effectiveness and efficiency of therapeutic concepts. We therefore planned a study that was supposed to provide population based epidemiological data in the field of severe brain trauma from the site of the accident until discharge from hospital. All 90.000 prehospital emergencies that were cared for by emergency physicians in Cologne from January 1990 until December 1996 were screened for identification of severe brain trauma. Their clinical course was reviewed using standard records and patients were included if they had their accident within the city of Cologne and fullfilled the final inclusion criteria of GCS ≤ 8 or AISHead ≥3. 650 eligible patients were identified of whom 530 had complete datasets (follow-up 80 %). Univariate statistical analysis was performed for all relevant variables. The main study endpoints were incidence and outcome of severe brain trauma. The annual incidence of severe brain trauma in Cologne (1 mio. inhabitants) was 93. The average age was 39 years and 71 % of the patients were male. The average prehospital GCS was 6.8, the average prehospital Trauma Score was 8.3 points. 49 % of the study population suffered from multiple injuries. The overall mortality rate was 46,6 %. 60 % of deaths occurred within the prehospital setting. The incidence of severe brain trauma in Cologne in this study was significantly lower compared to what could be expected from the litera-ture. The overall mortality was high, especially the high prehospital death rate is striking.
Comparison of the axonal and glial reactions between the caudal	and rostral border in the cryoinjured dorsal funiculus of the rat spinal cord
Authors: Kitada Masaaki , Mizoguchi Akira , Tohyama Koujiro , Ohtsubo Akinori , Fujimoto Etsuko , Chakrabortty Shushovan , Ide Chizuka
Published: December 2024

Axonal and glial reactions to traumatic injury were compared between the caudal and rostral border of the lesion after freeze-injury to the C3 dorsal funiculus by attaching a liquid nitrogen-cooled copper probe to the dorsum of the rat spinal cord. The axonal and glial changes were examined up to 60 days postoperative by light and electron microscopy and immunohistochemistry for neurofilaments. Regenerative axonal changes and the appearance of numerous undifferentiated cells were found at the caudal border 7 days after cryoinjury. In contrast, such axonal and cellular reactions were scarce at the rostral border. Undifferentiated cells clearly manifested their phenotypes by differentiating into oligodendrocytes or astrocytes 11 days postinjury. The results indicated that glial cell reactions occurred in association with regenerative axonal changes at the proximal stump of the injured nerve fibers, suggesting that regenerating and demyelinated naked axons could be responsible for the appearance of the immature glial cells.
Development of a reconstituted nerve in a three-dimensional	collagen gel under tension populated with fibroblasts and Schwann cells
Authors: Dubuisson Annie S. , Lapiere Charles M. , Nusgens Betty V.
Published: December 2024

Our aim is to devise an artificially reconstituted nerve segment made of a three-dimensional collagen gel populated with aligned fibroblasts and Schwann cells. Collagen lattices were prepared by mixing concentrated medium, a type I collagen solution and rat Schwann cells (SC), rat neural fibroblasts (nF) or human dermal fibroblasts (dF) and allowed to polymerize at 37 °C. In these free-floating lattices, nF and dF retracted the gel more than SC. All cells appeared to be elongated and oriented at random. Rat cells obtained by enzymatic digestion of nerves undergoing wallerian degeneration retracted the gel at a larger extent than cells from intact nerves. Rectangular lattices restrained at each extremity acquired a paraboloid shape upon retraction by neural or dermal F reflecting the mechanical tension developed by these cells on their support. Adult SC alone produced a faint paraboloid even at high cell density while SC associated with nF developed a paraboloid similar to that obtained with nF alone. The mechanical force developed by dermal F and SC in the restrained lattice was measured by strain gauges and found much higher for F than for SC. In restrained lattices, both types of F were elongated and aligned to the long axis of the gel while SC elongated but not necessarily in a parallel fashion. The central portion of a mixed nF-SC collagen restrained lattice produces a flattened cylindric segment made of longitudinally oriented col-lagen fibrils, F and SC, which could represent a promising material for preparation of nerve grafts. An original plastic mould was devised to allow the preparation of cylindrical segments of free or restrained collagen lattices in view of in vitro and in vivo regeneration studies.
A synthesized pyrimidine compound, MS-818, promotes walking	function recovery from crush injury of the sciatic nerve through its indirect	stimulation of Schwann cells
Authors: Fukuyama Ryuichi , Ohta Mitsuhiro , Ohta Kiyoe , Saiwaki Takuya , Fushiki Shinji , Awaya Akira
Published: December 2024

Purpose: We evaluated the effects of the drug MS-818 (2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate), a synthesized pyrimidine compound, on regeneration in crush-injured sciatic nerves of rats. Methods: MS-818 at 1.0 or 10 mg/kg or the vehicle was intraperitoneally injected into rats daity. The pinch test (PT) was performed 5 days after the operation. Walking function recovery was assessed by the sciatic nerve functional index (SFI). Time-dependent changes in the levels of transcripts of nerve growth factor (NGF) and apolipoprotein E (ApoE) genes were monitored by RT-PCR. NGF peptide levels retained in the crushed nerves of rats 5 days after surgery and in the culture medium of IMS32 cells, a mouse Schwann cell line, incubated for 24 h with high or low doses of MS-818, were measured by enzyme immunoassay. Results: The PT showed that MS-818 injection promoted axonal elongation by 19.3 % compared to the vehicle injected control (n = 7, *p < 0.03). The SFIs 3 weeks after injection of MS-818 at 1.0 mg/kg and 1 0 mg/kg were significantly increased to the control level (n = 5-6, **p < 0.006 and *p < 0.03, respectively). Injection of MS-818 at 1.0 mg/kg induced NGF gene expression more than twofold compared to that of the control at 5 to 6 days after surgery (n = 4). NGF levels in crushed nerves after MS-818 injection at 1.0 and 10 mg/kg tended to be higher than those of the vehicle-injected controls by approximately 20 %, although it did not reach statistical significance. Treatment of IMS32 cells with MS-818 failed to give rise to NGF overproduction and its secretion into the culture medium. Conclusions: These present evidences suggest that MS-818 enhances functional recovery of damaged sciatic nerves by promoting axonal sprouting through indirect activation of Schwann cells and that local production of NGF rnay be activated by MS-818.
Lower limb muscle activity in ambulatory children with cerebral	palsy before and after the treatment with Botulinum toxin A
Authors: Hesse S. , Brandl-Hesse B. , Seidel U. , Doll B. , Gregoric M.
Published: December 2024

Purpose: The study investigated the effect of Botulinum toxin A on the gait and lower limb muscle activity of ambulatory CP children. Methods: 19 spastic diplegic and 4 left hemiparetic CP children were injected with a mean dose of 23.5 units of Botulinum toxin A/kg body weight into the gastrocnemius and hamstring muscles. Muscle tone and gait analysis including the kinesiological electromyogram of the shank and thigh muscles were assessed before and four weeks after injection and compared with the help of a multivariate analysis (p < 0.05). Results: Botulinum toxin A caused a definite reduction of plantarflexor, knee and hip hypertonia in 21 children, resulting in a more plantar grade and erect gait in 17 children four weeks after injection. Gait analysis showed a statistically significant improvement in peak ankle dorsi-flexion and knee extension during stance, and the length of the force point of action under both feet increased. Electromyography revealed sig-nificantly less co-contraction of the lower leg muscles, due to a more phasic instead of a tonic activity of the tibialis anterior muscle, and an improved activation pattern of the left rectus and biceps femoris muscles. Conclusions: The present study demonstrated that the injection of Botulinum toxin A resulted in a more mature muscle activation pattern of CP children. Most of the children walked more plantigrade and erect, the functional gait parameters, however, did not change.
Acceleration of peripheral nerve regeneration following FK506	administration
Authors: Jost, Sarah C. , Doolabh Vaishali B. , Mackinnon Susan E. , Lee Michelle , Hunter Daniel
Published: December 2024

Purpose: The severe functional and sensory deficits seen following injury to peripheral nerves makes facilitation of nerve regeneration a primary goal of the reconstructive surgeon. This study examines whether daily administration of FK506 or Cyclosporin A expedites peripheral nerve regeneration following neurotmetic injury in a rat model Methods: Inbred Buffalo rats were randomized to three experimental groups. Group I rats served as untreated controls. Rats in groups II and III received daily subcutaneous CsA (5 mg/kg), and FK506 (1 mg/kg), respectively. Each animal underwent unilateral posterior tibial nerve transection with immediate epineurial reapproximation. Functional recovery of the injured limb was assessed by serial walking track analysis. Nerve regeneration was assessed histomorphometrically via light microscopy. Results: Return of hindlimb function in control animals occurred at 32 days post injury. CsA and FK506-treated transection animals recovered at 26 and 18 days post injury, respectively. Statistically significant greater fiber density and percent neural tissue were seen in FK506- treated animals compared to control animals four weeks post transection. Conclusions: This data suggest that the daily systemic administration of both CsA and FK506 accelerate the rate of functional regeneration, following neurotmetic injuries in tbc rat model. FK506's effect on nerve growth is significantly greater than that of CsA.
Is there an optimal age for recovery from motor cortex lesions?	II. behavioural and anatomical consequences of unilateral motor cortex lesions	in perinatal, infant, and adult rats
Authors: Kolb Bryan , Cioe Jan , Whishaw Ian Q.
Published: December 2024

Purpose: The purpose of this study was to compare the behavioural and anatomical effects of unilateral motor cortex ablation in neonatal, infant, and adult rats. Methods: Rats were given unilateral lesions of the motor cortex on the day of birth (P1), at ten days of age (P10), or in adulthood. They were trained on several motor tasks (skilled forelimb reaching, beam traversing, tongue extension), general motor activity, and a test of spatial learning (Morris water task). Results: Although all lesion groups were equally impaired at skilled reaching with the forelimb contralateral to the lesion, rats with P1 lesions also were impaired at traversing a narrow beam and at learning the Morris task. Gross anatomical analyses revealed that the P1 rats had smaller brains than the other groups, a result that may account for the larger behavioural deficits in the P1 group. Analysis of Golgi-Cox stained neurons showed that relative to control groups, all lesion groups showed an increase in dendritic length in the basilar dendrites of layer III pyramidal cells and, paradoxically a decrease in length of the apical dendrites of the same cells. Conclusions: The bilateral alterations in dendritic organization following the motor cortex lesions suggest that there has been a bilateral reor-ganization of intrinsic cortical connectivity following motor cortex lesions at any age. These alterations in connectivity are likely not identical in the young and adult animals, however, because relative to controls, both the young operated groups, but not the adult group, showed a bilat-eral drop in spine density in the basilar dendrites of layer V pyramidal cells. These findings are discussed with respect to the idea that there may be critical ages in development in which animals can use anatomical modifications to compensate for deficits produced by cortical injury.
Single administration of GDNF into the striatum induced protection	and repair of the nigrostriatal dopaminergic system in the intrastriatal	6-hydroxydopamine injection model of hemiparkinsonism
Authors: Aoi Mizuho , Date Isao , Tomita Susumu , Ohmoto Takashi
Published: December 2024

Purpose: Neurotrophic factor delivery into the brain is a promising approach in the treatment of Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent neurotrophic factors for dopaminergic neurons. Although multiple injections of GDNF into the brain are commonly performed in experimental studies, the present study investigates the efficacy of using a single injection of GDNF, which may be useful in elinically applying this treatment. Methods: Unilateral 6-hydroxydoparnine (6-OHDA) administration into the striatum was perforrned in Sprague-Dawley rats to create a partial lesion of the nigrostriatal DA system. These parkinsonian model rats received a single injection of human recombinant GDNF into the same portion of the striatum either 24 h before or 4 weeks after 6-OHDA treatrnent. Results: GDNF injected into the striatum before 6-OHDA administration potently protected the dopaminergic system, as shown by the numbers of mesencephalic dopaminergie neuron cell bodies and dopaminergic nerve terminal densities in the striatum. Dopaminergic neuron cell bodies and fiber densities were also significantly restored when GDNF was given after 6-OHDA administration, although the degree of restoration was lower than in the protective experiment. ODNF administration ameliorated apomorphine-induced rotational behavior in animals receiving it either before or after 6-OHDA treatment. However, the degree of improvement was less prominent when GDNF was iniected after 6-OHDA. Conclusion: Intracerebral GDNF adininistration exerts both protective and regenerative effects on the nigrostriatal dopaminergic system, a finding which may have implications for the development of new treatment strategies for Parkinson's disease.
Changes in BDNF and neurotrophin receptor expression in	degenerating and regenerating rat retinal ganglion cells
Authors: Hirsch Sabine , Labes Monika , Bähr Mathias
Published: December 2024

Purpose: Exogenously applied BDNF has been shown to rescue rat retinal ganglion cells (RGCs) from axotomy-induced apoptotic death, presumably via activation of its high affinity receptor TrkB. Since both TrkB and BDNF are endogenously expressed in RGCs, auto- or para-crine neurotrophic loops in the retina may be involved. In the present study, we investigated whether expression levels of BDNF, TrkA, TrkB, TrkC and p75 protein in RGCs are specifically regulated following axonal lesion and during regeneration of optic fibres in the adult rat. Methods: By double labelling retinal cryosections with Fluorogold and respective antibodies we determined the percentage of RGCs expressing the above-mentioned markers. In addition, mRNA levels of BDNF and TrkB were measured using quantitative RT-PCR. Results: Compared to controls the number of BDNF-positive RGCs increased twofold 2 days after axotomy and the percentage of RGCs expressing TrkB was elevated by 50 %. Correspondingly, mRNA levels of BDNF increased about twofold 2 days after axotomy. During regen-eration, the percentage of BDNF-immunoreactive RGCs was further elevated compared to axotomy alone. The number of TrkA-positive RGCs doubled after axotomy, whereas no significant change in TrkC expression was observed. P75 expression was not detected in adult rat RGCs. Conclusion: Our results suggest that intrinsic rescue mechanisms may contribute to short term neuronal survival and axonal regeneration of RGCs after axonal lesions.
Diethyldithiocarbamate (DEDC) impairs neuronal recovery following	sciatic nerve injury in rats
Authors: Tariq Mohammad , Arshaduddin Mohammed , Biary Nabil , Al Deeb Saleh , Al Moutaery Khalaf
Published: December 2024

Purpose: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC has received considerable attention because of its clinical applications and potential role in mediating both the toxic and therapeutic actions of disulfiram which is frequently used for alcohol aversion therapy. DEDC is known for its multiplicity of action that exerts both pro- and antioxidant effects. In rodents DEDC has been shown to produce neuroprotective as well as neurotoxic effects. The purpose of this study was to examine the effect of DEDC on neurological recovery following sciatic nerve crush injury (SNCI) in rats. Methods: Adult female Wistar rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and then once daily for 60 days. The animals were observed for sciatic functional index (walking deficit), electrophysiological and histological changes. Vitamin E level was measured to deter-mine antioxidant status of sciatic nerve. Results: Crush injury to the sciatic nerve resulted in a significant impairment of functional response which gradually recovered over a period of 22 days. Treatment of animals with DEDC caused a significant delay in functional recovery which was accompanied by poor histo-logical and electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a significant decrease in vitamin E levels in both injured and uninjured sciatic nerves. Conclusions: Our results demonstrate that exposure to DEDC adversely affects recovery from peripheral nerve injury. The delay may to some extent be attributed to DEDC induced oxidative stress.
Conditionally immortal neuroepithelial stem cell grafts restore	spatial learning in rats with lesions at the source of cholinergic forebrain	projections cholinergic forebrain projections Conditionally immortal	neuroepithelial stem cell grafts restore spatial leaming in rats with lesions	at the source of cholinergic forebrain projections
Authors: Grigoryan G.A. , Gray J.A. , Rashid T. , Chadwick A. , Hodges H.
Published: December 2024

Purpose: Loss of cholinergic projections from the basal forebrain (BF) to the cortex and from the medial septal area (MSA) to tbe hippocampus is a reliable correlate of cognitive deficits in aging and Alzheimer's disease (AD). We assessed the capacity of grafts of the conditionally immortal MHP36 clonal stem cell line to improve spatial learning in rats showing profound deficits after lesions to these projections. Methods: Rats were lesioned by infusions of S-AMPA unilaterally into BF or bilaterally into both BF and MSA. MHP36 cells were implanted ipsilaterally in cortex or basal forebrain two weeks after unilateral BF lesions, and in cortex and hippocampus bilaterally six months after bilateral BF-MSA lesions. Intact and lesion-only controls received vehicle. Six weeks later rats were assessed in spatial learning and memory tasks in the water maze, and then perfused for identification of grafted cells by β-galactosidase immunohistocheniistry. Results: Lesioned rats with MHP36 grafts, whether implanted two weeks or six months after lesioning, learned to find a submerged platform in the water maze as rapidly as intact controls, and showed a strong preference for the platform quadrant on probe trials, whereas lesioned controls were impaired in all measures. Grafted cells of both neuronal and glial morphologies, migrated away from cortical implantation sites in BF Lesioned rats to the striatum, thalamus and basal forebrain lesion area. Cells implanted in basal forebrain showed a similar distribution. In rats with bilateral BF-MSA lesions, grafts implanted in the hippocampus migrated widely through all layers but cortical grafts largely escaped up the needle tract into the meninges. Conclusions: Although MHP36 grafts were functionally effective in both lesion models, the site and age of lesions and site of implantation influenced the pattern of engraftment. This flexibility encourages the development of conditionally immortal human stem cell lines with similar capacities for functional repair of variable neuronal degeneration in AD or aging.
The Effect of Methylprednisolone on Caspase-3 Activation after Rat	Spinal Cord Transection
Authors: Li Xiuming , Oudega Martin , Dancausse Hector A. , Levi Allan D.O.
Published: December 2024

Purpose: Caspase-3 is known as a crucial effector for apoptotic cell death. Apoptosis has recently been recognized as an important cell death mechanism after spinal cord injury (SCI). This study attempts to define the effect of methylprednisolone (MP) on the activation of caspase-3 in the lesioned area following SCI. Methods: Forty-eight rats with a complete transection of the thoracic spinal cord received a placebo or MP (30 mg/kg, iv.) at 5 min, 2 and 4 h post-injury and were then sacrificed at 12, 24 h, 3 or 7 days thereafter. Results: Caspase-3 positive cells in the lesioned area were immunocytochemically observed in both cord stumps and decreased in number with increasing distance from the lesion site. More caspase-3 positive cells were present in the MP-treated group than the control group at all time points, but the differences were not statistically significant. Conclusion: These results suggest that the MP-induced decrease of tissue loss following SCI may not involve a reduction of apoptotic cell death.
Quality of life in patients with spinal cord injury-basic issues,	assessment, and recommendations
Authors: Wood-Dauphinée S. , Exner G. , the SCI Consensus Group
Published: December 2024

Introduction: Spinal cord injury (SCI) often causes severe disabilities. The degree of functional impairment strongly depends on the level and completeness of lesion (tetraplegic, paraplegic). But evaluation of outcomes also needs to consider the broader concept of health-related quality of the life (HRQL) for SCI patients. A multinational group of clinicians and researchers assessed this concept and revieved the available instruments for measurement of quality of life in this group of patients.

Time points: Phase I is in the acute clinic; phase II during rehabilitation; phase III after discharge home. Annual follow-up investigations should be maintained. The phase of initial care (phase 0) is important for prognosis and should, therefore, be part of the documentation.

Instruments: Criteria used to evaluate current QoL measures: reliability, validity, responsiveness, availability of translations, application in SCI patients, existing population norms. Several specific instruments or subscales exist for the following domains: physical and psychological functioning, pain, and handicap. Well-known generic measures of HRQL also have been applied to SCI patients, and a disease-specific instrument has been developed (SCIQL-23). A variety of subjective quality of life measures were evaluated as well.

Group consensus / guideline: Prior to discharge from rehabilitation, the group suggested the use of the Functional Independence Measure, the Hospital Anxiety and Depression Scale and a Visual Analogue Scale for pain. Following discharge from the acute clinic, the SF-36, the Craig Handicap Assessment and Reporting Technique, the Quality of Well-being Scale, or the Life Satisfaction questionnaire were proposed. However, the evidence supporting the use of these instruments is sparse.
Spontaneous recovery of locomotion induced by remaining fibers	after spinal cord transection in adult rats
Authors: You Si-Wei , Chen Bing-Yao , Liu Hui-Ling , Lang Bing , Xia Jie-Lai , Jiao Xi-Ying , Ju Gong
Published: December 2024

Purpose: A major issue in analysis of experimental results after spinal cord injury is spontaneous functional recovery induced by remaining nerve fibers. The authors investigated the relationship between the degree of locomotor recovery and the percentage and location of the fibers that spared spinal cord transection.

Methods: The spinal cords of 12 adult rats were transected at T9 with a razor blade, which often resulted in sparing of nerve fibers in the ventral spinal cord. The incompletely-transected animals were used to study the degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB rating scale, in correlation to the extent and location of the remaining fibers.

Results: Incomplete transection was found in the ventral spinal cord in 42% of the animals. The degree of locomotor recovery was highly correlated with the percentage of the remaining fibers in the ventral and ventrolateral funiculi. In one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus were able to sustain a certain recovery of locomotion.

Conclusions: Less than 5% of remaining ventrolateral white matter is sufficient for an unequivocal motor recovery after incomplete spinal cord injury. Therefore, for studies with spinal cord transection, the completeness of sectioning should be carefully checked before any conclusion can be reached. The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery.
Neuronal post-stroke plasticity in the adult
Authors: Rossini Paolo M. , Forno Gloria Dal
Published: December 2024

Contrary to what previously believed, recent research advances have demonstrated that the adult brain has a certain capacity for plastic reorganization and self-repair after a lesion such as cerebrovascular accidents. The mechanisms subtending post-stroke recovery are probably complex and operating at different levels, from molecular to synaptic to anatomical reorganization. The integrated use of functional neuroimaging techniques, by overcoming the limitations of each specific methodology is likely to shed much light on plasticity mechanisms. In this review we discuss the neuroanatomy and neurophysiology possibly underlying reorganization of the central nervous system, as well as the experimental evidence of "in vivo" post-stroke plasticity. Better understanding of these mechanisms can provide neurorehabilitation with powerful tools in designing and implementing new therapeutic approaches to stroke patients both in the acute and the chronic stages after a brain tissue lesion has occurred and stabilized.
The reorganization of the motor system in primates after the loss	of a limb
Authors: Kaas Jon H. , Qi Hui-Xin
Published: December 2024

As a result of an extensive search, we were able to obtain a limited number of macaque monkeys, New World squirrel monkeys, and prosimian galagos years after they had received a therapeutic amputation of a forelimb or hindlimb as a treatment for injury. Forelimb or hindlimb regions of primary motor cortex, M1, were stimulated in these primates with microelectrodes using amounts of current just sufficient to evoke a movement. Results were compared to those obtained from normal primates or from M1 contralateral to the intact limb in the same primates. In all cases, more sites in M1 contralateral to the amputated limb evoked movements of the limb stump and muscle in the adjoining shoulder or hip. In two of the macaque monkeys, injections in M1 reveal more widespread intrinsic connections than in normal M1, and in several monkeys and galagos, injections of tracers in muscles of the stump, shoulder, or hip labeled spinal cord motor neurons that normally project to the distal limb. These anatomical results suggest that the functional changes in M1 following amputation are mediated in part by the formation of new connections.
Advances in adjuvant pharmacotherapy for motor rehabilitation:	Effects of levodopa
Authors: Scheidtmann Klaus
Published: December 2024

Hemiparesis is common after stroke and often severely disabling. Until very recently, the only therapeutic option for motor recovery was physiotherapeutic training. Experimental animal studies have shown that when applied in addition to exercises pharmacological interventions that affect the norepinephrine system can enhance the rate of functional motor recovery. These effects were observed when an increase in norepinephrine concentration in the CNS was pharmacologically induced. We recently showed that 3 weeks of single daily doses of 100 mg L-dopa, which is metabolized into norepinephrine in the brain, increase the efficacy of physiotherapy in hemiparetic stroke patients. Two additional randomized controlled trials with stroke patients also demonstrated the clinical relevance of this approach for motor recovery and independence in activities of daily living. Modifying effects of other frequently occurring clinical symptoms such as spasticity, neglect, and attention were also investigated. Thus, in view of its minimal side effects, L-dopa can be recommended in conjunction with exercise therapy to improve the functional outcome in stroke rehabilitation.