bluuebunny/crossref_metadata_2025 huggingface dataset:
Alignment of collagen and laminin-containing gels improve nerve	regeneration within silicone tubes
Authors: Verdú Enrique , Labrador Rafael O. , Rodríguez Francisco J. , Ceballos Dolores , Forés Joaquim , Navarro Xavier
Published: December 2024

Purpose: Placement of extracellular matrix components has been used as a mean to enhance axonal growth across nerve long gaps repaired by tubulization. However, such matrices may impede axonal regeneration depending on its density and microgeometry. Methods: Silicone tubes were prefilled with collagen or laminin-containing gels and implanted into a 6 mm gap, a length considered limiting for regeneration, in the mouse sciatic nerve. Gels were polymerized prior to implantation either in horizontal position or subjected to gravitational (in vertical position) or to magnetic forces to induce longitudinal alignment of the fibrils. Recovery of motor, sensory and sudomotor functions in the hindpaw was evaluated during 4 months postoperation. Results: Reinnervation started earlier and achieved slightly higher levels with aligned collagen gels than with the horizontal gel. For the three groups repaired with tubes with Matrigel, there was a gradation of the functional results, reinnervation started earlier and reached higher values in matrix with magnetically-induced, longitudinal orientation than with the horizontal gel, whereas gravitational alignment followed an intermediate evolution. Final morphological evaluation showed more dense residual mass of collagen than of Matrigel at the center of the regenerate nerves. The number of myelinated fibers was increased in tubes with alignment compared to horizontal gels. Conclusions: Alignment of collagen and laminin gels within a silicone tube increases the success and the quality of regeneration in long nerve gaps. The laminin gel performed better than the collagen gel under each condition tested. The combination of an aligned matrix with embedded Schwann cells should be considered in further steps for the development of an artificial nerve graft for clinical application.
Descending systems contributing to locomotor recovery after mild	or moderate spinal cord injury in rats: experimental evidence and a review of	literature
Authors: Michele Basso D. , Beattie Michael S. , Bresnahan Jacqueline C.
Published: December 2024

Purpose: Locomotor recovery after spinal cord contusion injury (SCI) may be mediated by descending axons spared at the lesion epicenter. Greater axonal sparing is associated with more extensive recovery. Therefore, we identified the source and relative proportion of spared axons associated with extensive or limited locomotor recovery after SCI. Methods: Female Sprague Dawley rats underwent mild or moderate SCI using the OSU device. Results: Locomotor recovery was greater for the mild than moderate group with the primary differences being restitution of limb coordination, very little toe dragging and minor paw rotation. Conclusions: The following brain nuclei with substantial neuronal labeling after mild but not moderate SCI may play an important role in locomotor recovery: raphe pallidus and magnus, ventral medullary and pontine reticular formation, lateral vestibular nucleus, red nucleus and locus coeruleus. We review the normal anatomical distribution of descending systems to the lumbar cord in rat and the role they play in motor control.
Peripheral markers of brain damage and blood-brain barrier	dysfunction
Authors: Marchi Nicola , Rasmussen Peter , Kapural Miranda , Fazio Vince , Kight Kelly , Mayberg Marc R. , Kanner Andrew , Ayumar Barbara , Albensi Ben , Cavaglia Marco , Janigro Damir
Published: December 2024

Purpose: Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100β and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100β levels sometimes rise in the absence of neuronal damage, suggesting that S100β is a marker of BBB rather than neuronal damage.

Methods: We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy.

Results: Serum S100β increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100β increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100β release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100β are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia.

Conclusions: Thus, S100β in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100β are indicators of prior brain damage and bear clinical significance as predictors of poor outcome or diagnostic means to differentiate extensive damage from minor, transient impairment.
Serum S-100B protein as a molecular marker in severe traumatic	brain injury
Authors: Raabe Andreas , Kopetsch Olaf , Woszczyk Alina , Lang Josef , Gerlach Rüdiger , Zimmermann Michael , Seifert Volker
Published: December 2024

Purpose: There is growing evidence that S-100B protein may be used as a novel biochemical marker of brain cell damage, measured by a simple blood test. In this paper, we summarize the current knowledge about S-100B serum measurements in severe head injury and address actual controversies.

Methods: The material of the present analysis consists of a MEDLINE literature search for S-100 and severe head injury from 1966 to 2003. Studies of S-100B in severe head injury were reviewed for their information about the potential clinical value of this marker.

Results: A total of 18 clinical studies were identified and reviewed. Peak values of serum S-100B were demonstrated to have the highest correlation to any endpoint parameter. Admission values also have a significant correlation to injury severity and outcome but show a highly time dependent temporal course. There is extracranial release of S-100B in multitrauma patients in the first 48 hours, but the impact is limited as many studies have found a clear relationship between S-100B and injury severity, imaging findings and outcome.

Conclusion: S-100B belongs to a new generation of molecular serum markers of brain damage. These markers will have potential as a surrogate outcome marker or monitoring parameters for both clinical and experimental settings.
Allopregnanolone, a progesterone metabolite, enhances behavioral	recovery and decreases neuronal loss after traumatic brain injury
Authors: He Jun , Hoffman Stuart W. , Stein Donald G.
Published: December 2024

Purpose: In the current study we investigated whether allopregnanolone, a metabolite of progesterone, could replicate progesterone's beneficial effects in promoting spatial learning ability after bilateral medial prefrontal cortex contusions in rats. Allopregnanolone has been shown to enhance GABA neurotransmission, whereas its isomer epiallopregnanolone does not have this property. Thus, epiallopregnanolone was chosen as a control substance to examine further the role of GABA transmission in post-trauma neuroprotection.

Methods: After the contusion, rats were given 4 mg/kg treatment of either allopregnanolone or epiallopregnanolone for five consecutive days beginning 1hr post-injury. Control groups only received vehicle treatment at the same time points. A spatial learning task (Morris Water Maze, MWM) was performed at 7 days post-injury for 10 days. Subsequent histological analyses of brain tissue were conducted to determine quantitatively the neuronal losses in both the mediodorsal nucleus of the thalamus (MDN) and the nucleus basalis magnocellularis (NBM).

Results: Allopregnanolone-treated rats showed better performance in the MWM compared to the vehicle-treated injury group. The histological analyses also revealed that the allopregnanolone-treated injury group had less neuronal loss in both the MDN and the NBM compared to the vehicle-treated injury group. In contrast, epiallopregnanolone did not facilitate MWM performance or reduce neuronal loss in the MDN and the NBM after TBI.

Conclusion: Based on our findings, we suggest that allopregnanolone may mediate the effects of progesterone in promoting cognitive and morphological recovery from TBI through, among others, its direct or indirect effects on GABA-modulated neurons in the MDN and the NBM.
Macrophage stimulation using a group B-streptococcus exotoxin	(CM101) leads to axonal regrowth in the injured optic nerve
Authors: Ohlsson Marcus , Mattsson Per , Wamil Barbara D. , Hellerqvist Carl G. , Svensson Mikael
Published: December 2024

Purpose: A group B-streptococcus exotoxin (CM101) was administered following optic nerve injury in adult rats in order to analyze putative effects on macrophages, glial scar formation and regrowth of axons in the lesioned optic nerve.

Methods: After a standardized intraorbital optic nerve crush, animals were randomized to treatment with CM101 (30 μm/kg body weight, iv, repeated every other day) or vehicle alone. Morphology (semithin sections) and immunohistochemistry directed towards macrophages (ED1), neurofilament (NF), astrocytes (GFAP) and regenerative sprouts (GAP43) were employed at different time-points up to 28 dpi.

Results: A significant increase of ED1-positive macrophages (p < 0.05) was observed at 7, 14 and 28 dpi in treated animals compared to untreated, indicative of macrophage stimulation. Less degenerative structures were found in sections distal to the injury in treated animals, seemingly due to a pro-phagocytic effect. Reactive gliosis was significantly (p < 0.05) less pronounced in CM101-treated animals. The presence of GAP43-positive sprouts and neurofilament-positive neurites distal to the lesion in treated animals indicate regrowth of axons crossing the glial scar.

Conclusion: Treatment with group B-streptococcus exotoxin leads to macrophage stimulation, increased phagocytosis of inhibitory debris, and a less dense reactive gliosis, which in turn allows for regrowth of axons through the glial scar.
Neuromodulation paired with learning dependent practice to enhance	post stroke recovery?
Authors: Walker-Batson D. , Smith P. , Curtis S. , Unwin D.H.
Published: December 2024

Over the past two decades, experimental studies following brain injury have shown that the central nervous system is dynamic and malleable to internal and external inputs. Neuromodulation and/or direct manipulation of motor and sensory experience can modify brain plasticity and functional outcome after experimental lesions. Specifically, pharmacologic modulation has been found to facilitate recovery of various behavioral deficits following occlusive injury. Additionally, the behavioral experience that induces long-term plasticity in motor and sensory maps after injury appears to be limited to those that entail the development of new skills. These data have strong application to human rehabilitation. This review will: (1) overview critical experimental studies that show that pharmacologic manipulation and/or specific behavioral experience may modify the functional organization of the injured brain and (2) review beginning studies which are exploring the application of this knowledge clinically.
Reorganisation of cerebral circuits in human ischemic brain	disease
Authors: Seitz Rüdiger J. , Bütefisch Cathrin M. , Kleiser Raimund , Hömberg Volker
Published: December 2024

Animal experiments suggest that reorganisation of cerebral representations is the neurobiological basis of post-lesional recovery. In human ischemic brain disease recovery is a dynamic and sustained process beginning after stroke manifestation. The mechanisms underlying recovery can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS).

In the acute stage, the mismatch area of the perfusion deficit and the impaired water diffusion as assessed by magnetic resonance imaging (MRI) shows the brain tissue that potentially can be rescued by thrombolysis or emergency carotid endarteriectomy. Since spontaneous motor recovery is a function of the corticospinal tract integrity, early reperfusion of ischemic tissue is critical. In the subacute and chronic stage after stroke, recovery of motor function was shown to take place irrespective of a concomitant affection of the somatosensory system. Functional MRI with simultaneous recordings of the electromyogram provides evidence that the abnormal activation of motor and premotor cortical areas in both hemispheres related to finger movements has a large interindividual variability. As evident from TMS, recovery results from regression of perilesional inhibition and from remote intracortical disinhibition. Repetitive training, constraint induced training and motor imagery can augment recovery promoting a re-emerging activation in the affected hemisphere.

Evolution of altered local perilesional and large-scale bihemispheric circuits appears to allow for post-lesional deficit compensation.
Lesion-induced and training-induced brain reorganization
Authors: Liepert J. , Hamzei F. , Weiller C.
Published: December 2024

Introduction: A stroke may modulate motor cortex excitability. We examined if distinct ischemic brain lesions are associated with a specific pattern of excitability changes. We also investigated the effects of a rehabilitative therapy on motor excitability.

Methods: In stroke patients, the consequences of a) a lesion in the central somatosensory system, b) a cerebellar lesion and c) a two week period of Constraint-induced movement therapy (CIMT), on motor cortex excitability were studied. Transcranial magnetic stimulation techniques and functional magnetic resonance imaging (fMRI) were employed.

Results: Patients with a lesion in the primary somatosensory cortex or in the ventroposterolateral nucleus of the thalamus had a decreased intracortical inhibition on the affected side. Patients with lesions in the territory of the superior cerebellar artery had a loss of intracortical facilitation and an increase of intracortical inhibition. Patients with cortical lesions undergoing CIMT had a loss of intracortical inhibition prior to therapy. After CIMT, changes of ICI were stronger in the lesioned than in the non-lesioned hemisphere but could result either in an increase of ICI or a reduction of ICI. In three patients fMRI results showed that cortical activation was less post CIMT as compared to pre-treatment activation. In parallel, ICI was reduced after treatment.

Conclusions: Our results suggest that, physiologically, central somatosensory influence on the motor cortex is inhibitory. In contrast, the cerebellum normally exerts a facilitatory influence on the motor cortex. CIMT induces changes of intracortical excitability mainly in the affected hemisphere.
Modulation of motor function and cortical plasticity in health and	disease
Authors: Celnik Pablo A. , Cohen Leonardo G.
Published: December 2024

Basic science studies demonstrated mechanisms of plasticity and metaplasticity. More recent human studies identified some of these mechanisms as operating in multiple areas of human cognition, such as learning and memory, and in functional recovery from lesions in the CNS, as in stroke. One of the goals of neurorehabilitation is the translation of these principles into rational strategies to promote recovery of function. Understanding the mechanisms and functional role of human plasticity could lead to the development of therapeutic options in situations in which there is virtually no treatment alternative, as in chronic stroke. We review some of the work performed to better understand the substrates and mechanisms underlying cortical plasticity and discuss some experimental approaches to enhance cortical plasticity and recovery of function, like cortical stimulation.
Recovery of gait and other motor functions after stroke: Novel	physical and pharmacological treatment strategies
Authors: Hesse S.
Published: December 2024

The gait-lab at Klinik Berlin developed and evaluated novel physical and pharmacological strategies promoting the repetitive practise of hemiparetic gait in line with the slogan: who wants to relearn walking, has to walk. Areas of research are treadmill training with partial body weight support, enabling wheelchair-bound subjects to repetitively practice gait, the electromechanical gait trainer GT I reducing the effort on the therapists as compared to the manually assisted locomotor therapy, and the future HapticWalker which will allow the additional practise of stair climbing up and down and of perturbations. Further means to promote gait practice after stroke was the application of botulinum toxin A for the treatment of lower limb spasticity and the early use of walking aids. New areas of research are also the study of D-Amphetamine, which failed to promote motor recovery in acute stroke patients as compared to placebo, and the development of a computerized arm trainer, Bi-Manu-T rack, for the bilateral treatment of patients with a severe upper limb paresis.
Interactive robots for neuro-rehabilitation
Authors: Hogan Neville , Krebs Hermano I.
Published: December 2024

This article reviews a decade of work aimed at developing effective interactive robotic tools to treat and understand motor impairment and disability. The success of an initial pilot study with acute-phase in-patients recovering from stroke prompted a larger study showing that these results could be replicated and a follow-up study showing that the benefits lasted. Studies of chronic-phase out-patients demonstrated that similar benefits could be obtained which also lasted and were accompanied by a concomitant reduction of pain. Exploration of the likely biology of recovery suggested an improvement of robotic treatment in the form of performance-based progressive therapy aimed at accelerating a process akin to motor learning postulated to underlie recovery. Initial studies of this method show a dramatic improvement over the previous successes. Kinematic studies of the recovery process show that, similar to the development of motor behavior in infants, it begins with stereotyped submovements and proceeds by progressively merging these to approach unimpaired motor performance.
Improving recovery of spinal cord-injured rats by	telomerase-driven human neural progenitor cells
Authors: Xu Guanghui , Li Xiaoxia , Bai Yun , Bai Jinzhu , Li Lingsong , Shen Li
Published: December 2024

Purpose: Human neural progenitor cells hold great promise for treating a variety of human neurological diseases such as spinal cord injury. One of the issues limiting this technology is how to expand neural progenitor cells in vitro to obtain sufficient number of cells for clinical transplantation. We have established a homogeneous population of human neural progenitor cells (hNPC-TERT) immortalized by the human telomerase reverse transcriptase (hTERT) gene. Then we studied whether these cells could differentiate into neural cells in vivo and improve the recovery of spinal cord-injured rats. Methods: The hNPC-TERT cells had been transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated through BBB locomotor scale and Motor Evoked Potentials. Additionally, the differentiation of hNPC-TERT cells was shown by immunocytochemistry. Results: As revealed by this animal model, hNPC-TERT cells developed into functional cells in the injured spinal cord and improved recovery from spinal cord injury in both locomotor scores and electrophysiological parameter in this animal model. Conclusions: This study is the first demonstration of the use of telomerase-driven human progenitor cells to treat spinal cord injury and should provide a new cell source for research of clinical application.
Understanding the pattern of functional recovery after stroke:	Facts and theories
Authors: Kwakkel Gert , Kollen Boudewijn , Lindeman Eline
Published: December 2024

Longitudinal studies show that almost all stroke patients experience at least some predictable degree of functional recovery in the first six months post stroke. However, the non-linear pattern as a function of time is not well understood. Several mechanisms are presumed to be involved, such as recovery of penumbral tissues, neural plasticity, resolution of diaschisis and behavioural compensation strategies. Rehabilitation is believed to modulate this logistic pattern of recovery, probably by interacting with these underlying processes. However, prediction models that are adjusted for the effects of time after stroke onset suggest that outcome is largely defined within the first weeks post stroke, although functional improvement has been found to extend beyond six months post stroke. In addition, kinematic studies show that functional improvement is more than recovery from impairments alone, suggesting that patients are able to improve in terms of gait or dexterity deficits using behavioural compensation strategies. Therefore, understanding the impact of task-dependent cortical activation patterns in non-invasive methods requires not only information derived from longitudinal studies pertaining to functional outcomes, but also a better understanding of what is kinematically learned during the acquisition of new skills.
Specific alteration of the Bax/Bcl2 ratio and cytochrome c without	execution of apoptosis in the hippocampus of aged baboons
Authors: Thees S. , Hubbard G.B. , Winckler J. , Schultz C. , Rami A.
Published: December 2024

Purpose: During ageing, there may be an age-associated loss of particular nerve cells in specific brain areas. Recent studies highlight the role of apoptosis in the normal ageing of the brain, heart, and skeletal muscle. Particular attention is paid to the role of cytochrome c release from mitochondria and alterations in the pro- and anti-apoptotic proteins, Bax and Bcl-2, respectively. The aim of this study was to investigate the potential occurrence of apoptosis in the hippocampus of aged baboons.

Methods: we have used the baboon as a potential non-human primate model for age-related pathology which afflicts the human brain. The TUNEL staining method was used to characterise the apoptotic cell death. For immunocytochemistry, antibodies directed against activated caspase-3, cytochrome c, Bcl-2 and Bax proteins were used.

Results: Our results show that in hippocampi of aged baboons the immunoreactivities of the antiapoptotic agent Bcl-2 was not prominently changed, of the proapoptotic agent Bax was upregulated, of the cytochrome c was redistributed, and that caspase-3 was not activated. The TUNEL-staining method revealed no apoptotic cell death in hippocampi of aged baboons.

Conclusions: This demonstrates that a specific alteration of the Bax/Bcl2 ratio occurs in the ageing baboon hippocampus which may directly influence the release of cytochrome c even without commitment to apoptosis.
Diffusion anisotrophy in the early stages of stroke can predict	motor outcome
Authors: Jang Sung Ho , Cho Sang-Hyun , Kim Yun-Hee , Han Bong Soo , Byun Woo Mok , Son Soo-Min , Kim Seong Ho , Lee Se Jin
Published: December 2024

Purpose: This study examined whether the degree of impairment of diffusion anisotrophy in the early stages of a stroke can predict the motor function outcome.

Methods: Thirty-one hemiplegic stroke patients were enrolled to this study. Diffusion anisotropy was measured by determining fractional anisotropy (FA) in the two ROIs (region of interests) at corona radiata (CR) and in the posterior limb of internal capsule (IC) during the early stages of stoke (average 7.9 days after stroke onset) and compared with motor outcome of the affected hand 3 months after stroke onset.

Results: Both ROIs (CR or IC) and lesion types (hemorrhage or infarction) did not have significant effect on the SBFA (symmetry of bilateral FA) and dMRC (medical research council score improvement), either. Patients with greater initial MRC score had significantly greater SBFA and dMRC. The regression equation between the dMRC (Y axis) and the SBFA (X axis) was semi-linear and significant (P < 0.05); for CR group, Y = 3.296 - 0.1192X + 0.0015X $^{2}$ ; for IC group, Y = 2.342 - 0.0533X +0.0007 $^{2}$ . The regression lines had 'threshold points' where a minute SBFA change would make a steep increase in dMRC.

Conclusion: The degree of impairment in diffusion anisotropy during the early stages of stroke appears to have the potential to predict motor outcome.
Motor recovery mechanism of diffuse axonal injury: A combined	study of transcranial magnetic stimulation and functional MRI
Authors: Jang Sung Ho , Cho Sang-Hyun , Kim Yun-Hee , You Sung H. , Kim Seong Ho , Kim Oryong , Yang Dong Suk , Son Su min
Published: December 2024

Purpose: The purpose of this study was to investigate the motor recovery mechanism following diffuse axonal injury (DAI) using transcranial magnetic stimulation (TMS) and functional MRI (fMRI).

Methods: Twenty-six hands of 13 control subjects and 14 affected hands of 8 patients (two hemiparetics and six quadriparetics) were evaluated. All the patients were initially diagnosedwith DAIand were evaluated after they had reached their maximal motor recovery. fMRI was performed at 1.5 T using a hand grasp-release movement paradigm and TMS was applied with a round coil over the vertex.

Results: fMRI revealed that both normal subjects and patients with DAI showed increased contralateral primary sensori-motor cortex activation during affected hand movement.The motor evoked potentials (MEPs) of the patient group was slightly delayed in latency and significantly increased in duration and turns. The relative MEP amplitude, phase, and excitatory threshold were not significantly different between the groups.

Conclusions: These findings may indicate the heterogeneity of the axons in the recovery process of the corticospinal tract. It seems that the motor recovery in patients who had suffered DAI was attributable to the recovery of the corticospinal tract.
Gait characteristics after gait-oriented rehabilitation in chronic	stroke
Authors: Peurala Sinikka H. , Titianova Ekaterina B. , Mateev Plamen , Pitkänen Kauko , Sivenius Juhani , Tarkka Ina M.
Published: December 2024

Purpose: To assess the effects of rehabilitation in thirty-seven ambulatory patients with chronic stroke during three weeks in-patient rehabilitation period. Methods: In the intervention group, each patient received 75 min physiotherapy daily every workday including 20 minutes in the electromechanical gait trainer with body-weight support (BWS). In the control group, each patient participated in 45 min conventional physiotherapy daily. Motor ability was assessed with the first five items of the Modified Motor Assessment Scale (MMAS $_{1-5}$ ) and ten meters walking speed. Spatio-temporal gait characteristics were recorded with an electrical walkway. Results: The MMAS $_{1-5}$ (p < 0.0005 and p = 0.005) and ten meters walking time (p < 0.0005 and p = 0.006) improved in both groups. The improvements in MMAS $_{1-5}$ and ten meters walking time did not differ between the groups (p = 0.217 and p = 0.195). Specific gait characteristics improved only in the intervention group, as seen in increased Functional Ambulation Profile score (p = 0.023), velocity (p = 0.023), the step lengths (affected side, p = 0.011, non-affected side p = 0.040), the stride lengths (p = 0.018, p = 0.006) and decreased step-time differential (p = 0.043). Furthermore, all gait characteristics and other motor abilities remained in the discharge level at the six months in the intervention group. Conclusions: It appears that BWS training gives a long-lasting benefit in gait qualities even in chronic stroke patients.
Treatment with magnesium improves reference memory but not working	memory while reducing GFAP expression following traumatic brain injury
Authors: Hoane Michael R.
Published: December 2024

Purpose: Previous studies have shown that administration of MgCl $_{2}$ in animal models of brain injury significantly improves functional recovery: however, few studies have examined cognitive recovery. The present study evaluated the effect of MgCl $_{2}$ pharmacotherapy on recovery of function following medial frontal cortex contusion injury.

Methods: Groups of rats were assigned to either MgCl $_{2}$ (1.0 mmol/kg) or saline treatment conditions and prepared with contusion injuries or shams. Drug treatment was administered 15 min and 24 hr following injury. Rats were examined on tests of sensorimotor performance (bilateral tactile adhesive removal) and cognitive ability (reference and working memory).

Results: Administration of MgCl $_{2}$ following injury significantly reduced the behavioral impairments observed on the bilateral tactile removal test. The acquisition of reference memory was also significantly improved compared to saline-treated rats; however, treatment did not improve working memory performance. Lesion analysis revealed that administration of MgCl $_{2}$ did not significantly reduce lesion size compared to saline-treatment. Examination of glial fibrillary acidic protein (GFAP) expression showed that MgCl $_{2}$ did significantly reduce the number of GFAP $^+$ cells.

Conclusion: These results indicate that MgCl $_{2}$ administration significantly improved behavioral outcome following injury in a task dependent manner and reduced GFAP expression.
Sutures as longitudinal guides for the repair of nerve defects –	Influence of suture numbers and reconstruction of nerve bifurcations
Authors: Scherman Peter , Kanje Martin , Dahlin Lars B.
Published: December 2024

Purpose: We investigated whether sutures could guide regeneration across bifurcated nerve defects and how the number of sutures influenced regeneration. Methods: Bilateral ten mm defects in the rat sciatic nerve were bridged by either two or six laps of longitudinal (8/0 polyglactin) sutures. Bilateral ten mm defects including the bifurcation of tibial and peroneal nerves were bridged by two laps to the tibial and four laps to the peroneal nerve on one side and vice versa on the other. Evaluation of tetanic force, weights of the gastrocnemius and caudal tibial muscles and morphometry of the nerves were performed at twelve weeks. Results: Simple defects bridged by six laps yielded a significantly greater number of myelinated axons compared to two laps. In the bifurcated defects a well defined two branched nerve structure was formed in all cases between the sciatic nerve and its peroneal and tibial branches. However, in the bifurcated model the tibial nerve attracted more axons than the peroneal irrespective of the number of suture laps. Conclusions: There is no simple correlation between the number of sutures and the number of regenerating axons but two suture laps may be insufficient for the repair of a rat sciatic nerve. Sutures supported reconstruction of new fascicles across bifurcated nerve defects.
On regenerative and collateral sprouting to hind limb digits after	sciatic nerve injury in the rat
Authors: Puigdellívol-Sánchez Anna , Prats-Galino Alberto , Molander Carl
Published: December 2024

Purpose: This study examines the proportions of regenerative and collateral sprouting to the skin after peripheral nerve injury.

Methods: In the first experimental paradigm, primary afferent neurones were pre-labelled with Diamidino Yellow (DY), injected in digit 3, followed by sciatic nerve section and repair. After three months of regeneration, digit 3 was re-injected with Fast Blue (FB) to label regenerating cells. Fluoro-Gold (FG) was applied to the femoral (FEM) and musculocutaneous (MC) nerves four days later to quantify their contribution to the innervation. In the second experimental paradigm, sciatic nerve was first sectioned and repaired. Three months later, the sciatic was resected, and digit 3 injected with FB. After four more days, FEM and MC were resected and FG injected in all digits.

Results: Neurones in dorsal root ganglion (DRG) L5 had a higher rate of correct reinnervation of digit 3 (44–72%) than neurones in DRG L4 (14–44%). Like in control cases, only occasional axons were traced from the FEM and MC. In the second experiment, only occasional labelled neurones appeared.

Conclusions: The results indicate differences in the capacity for correct peripheral sensory reinnervation between segmental levels, and that in this model collateral sprouting was practically non-existent compared to regenerative sprouting.
Object localization, discrimination, and grasping with the optic	nerve visual prosthesis
Authors: Duret Florence , Brelén Måten E. , Lambert Valerie , Gérard Benoît , Delbeke Jean , Veraart Claude
Published: December 2024

Purpose: This study involved a volunteer completely blind from retinis pigmentosa who had previously been implanted with an optic nerve visual prosthesis. The aim of this two-year study was to train the volunteer to localize a given object in nine different positions, to discriminate the object within a choice of six, and then to grasp it.

Methods: In a closed-loop protocol including a head worn video camera, the nerve was stimulated whenever a part of the processed image of the object being scrutinized matched the center of an elicitable phosphene. The accessible visual field included 109 phosphenes in a 14° × 41° area.

Results: Results showed that training was required to succeed in the localization and discrimination tasks, but practically no training was required for grasping the object. The volunteer was able to successfully complete all tasks after training. The volunteer systematically performed several left-right and bottom-up scanning movements during the discrimination task. Discrimination strategies included stimulation phases and no-stimulation phases of roughly similar duration.

Conclusion: This study provides a step towards the practical use of the optic nerve visual prosthesis in current daily life.
Electrical stimulation of denervated muscles of rats maintains	mass and force, but not recovery following grafting
Authors: Dow Douglas E. , Carlson Bruce M. , Hassett Cheryl A. , Dennis Robert G. , Faulkner John A.
Published: December 2024

Purpose: Denervated skeletal muscles lack contractile activity and subsequently lose mass and force generation. Prolonged periods of denervation prior to nerve-implant grafting limit the recovery of mass and force. We hypothesized that electrical stimulation during a period of denervation that maintains mass and force above the levels of denervated muscles enhances the recovery of mass and force following nerve-implant grafting.

Methods: The extensor digitorum longus (EDL) muscles of anesthetized rats were denervated, and a stimulator was implanted. Following 4 or 7 months of denervation, with or without electrical stimulation, the EDL muscles were removed, evaluated in vitro for mass and contractile properties, and then nerve-implant grafted into syngeneic rats. Unoperated, contralateral muscles were also evaluated and grafted.

Results: The hypothesis was not supported by the experimental data. Compared with values for 4- or 7-month denervated muscles, the stimulated-denervated muscles maintained higher mass and force, less prolonged time-to-peak tensions and half-relaxation times, and higher excitability. Nevertheless, the recovery of mass and force following grafting was not improved.

Conclusion: The factors within long-term denervated muscles that hinder recovery following grafting appear to be related primarily to factors associated with the duration of denervation and not to the level of atrophy and weakness prior to grafting.
Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on	cell death following traumatic brain injury in the rat
Authors: Kunz Tina , Marklund Niklas , Hillered Lars , Oliw Ernst H.
Published: December 2024

Purpose: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury.

Methods: Rofecoxib (n=23) or vehicle (n=20) were administered after FPI and for up to 3 days. Cell death was evaluated by Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay.

Results: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and TUNEL-positive cells were detected 12–72 h after FPI in the ipsilateral cortex and bilaterally in the dentate gyri. Fluoro-Jade B staining did not indicate a significant neuroprotective effect of rofecoxib (12–72 h) and neither did TUNEL staining. Quantificaton of the TUNEL staining in the ipsilateral cortex was ∼50% lower in the rofecoxib group at 12 and 24 h, but this did not reach statistical significance (p=0.06), and appeared unchanged at 72 h.

Conclusions: Rofecoxib lacked significant protective effect on early neuronal cell death in the FPI model of traumatic brain injury.
Peri-infarct reorganization in a patient with corona radiata	infarct: A combined study of functional MRI and diffusion tensor image	tractography
Authors: Jang Sung Ho , Ahn Sang Ho , Ha Jung Sang , Lee Se Jin , Lee Jun , Ahn Young Hwan
Published: December 2024

Purpose: We investigated the motor recovery mechanism of a stroke patient using functional MRI (fMRI) and diffusion tensor image tractography (DTT).

Methods: A 60 year-old woman with right corona radiata infarct presented with complete paralysis of the left upper extremity. The motor function of the affected upper extremity recovered slowly for 6 months to a point of nearly normal function. The motor function of the patient was evaluated by fMRI and DTT at 6 months from the onset. FMRI was performed at 1.5 T with timed hand grasp-release movements. DTT was performed using 1.5 T with a synergy-L Sensitivity Encoding head coil. Three dimensional reconstructions of the fiber tracts were obtained with FA < 0.3, angle > 45° as termination criteria.

Results: The contralateral primary sensorimotor cortex (SM1) was activated during both affected (left) and unaffected hand movements. DTT showed that the tracts originated from either SM1; the tracts then descended along the known pathway of the corticospinal tract, with the exception that the tract of the affected (right) hemisphere descended along the posterior portion of the infarcted corona radiata.

Conclusions: It seems that the motor function of the affected upper extremity was reorganized to the posterior portion of the infarcted corona radiata. This finding may reflect functional reorganization of the motor pathway following corticospinal tract damage. This appears to be one motor recovery mechanism of subcortical infarct.
Cognitive evaluation of traumatically brain-injured rats using	serial testing in the Morris water maze
Authors: Thompson Hilaire J. , LeBold David G. , Marklund Niklas , Morales Diego M. , Hagner Andrew P. , McIntosh Tracy K.
Published: December 2024

Purpose: As deficits in memory and cognition are commonly observed in survivors of traumatic brain injury (TBI), causing reduced quality of life for the patient, a major goal in experimental TBI research is to identify and evaluate cognitive dysfunction. The present study assessed the applicability of the serial Morris water maze (MWM) test to determine cognitive function following experimental TBI in the same group of rats which is particularly important for long-term studies and increasingly valuable for the evaluation of novel treatment strategies.

Methods: Male Sprague-Dawley rats (n=27) were anesthetized and subjected to either sham injury (n=9) or lateral fluid percussion (FP) brain injury of moderate severity (n=18). At 4 weeks post-injury, animals were trained in a water maze over 3 days (acquisition/learning phase) to find a submerged platform. At 8 weeks post-injury the hidden platform was then moved to the opposite quadrant, and animals were trained to find the new position of the platform over 3 days. Forty-eight hours later, animals were tested for memory retention in a probe trial in which the platform was not present.

Results: Brain-injured animals had significant learning impairment (p<0.0001), shifted-learning impairment (p<0.001) and memory retention deficits (p<0.01) in comparison to their sham-injured counterparts over the 8 week testing period. Swim speed and distance were not significantly altered by brain injury at any time point.

Conclusion: The validation of this testing paradigm using a clinically relevant experimental brain injury model is an important addition to behavioral outcome testing.
Stimulation of the basolateral amygdala improves the acquisition	of a motor skill
Authors: Bergado Jorge A. , Rojas Yeneissy , Capdevila Vladimir , González Odalys , Almaguer-Melian William
Published: December 2024

Purpose: We have previously shown that the stimulation of limbic structures related to affective life such as the amygdale can improve and reinforce neural plastic processes related to hippocampus-dependent forms of explicit memory, as spatial memory and LTP. We now assessed whether this effect is restricted to the mentioned structure and memory type, or represents a more general form of modulatory influence.

Methods: Young, male Sprague Dawley rats were implanted stereotactically with one electrode in the basolateral amygdala (BLA) and trained to acquire a motor skill using their right anterior limb. A group of animals received 3 trains of 15 impulses at the BLA 15 minutes after each daily training session. A second group of implanted animals was handled in the same way, but not stimulated, while a third group was not implanted. After reaching the training criterion the left motor cortex was mapped by the observation of the movements induced by stimuli applied in discrete points of the cortex.

Results: Cortical representation of the anterior limb was increased in all trained animals, showing that the motor cortex is involved in the acquisition of the new skill. Animals receiving stimulation of the BLA showed similar cortical changes, but learned faster than non-stimulated controls.

Conclusions: Reinforcement of neural plasticity by the activation of the amygdala is not restricted to hippocampus-dependent explicit memory, but it might represent a universal mechanism to modulate plasticity.
Functional brain imaging, clinical and neurophysiological outcome	of visual rehabilitation in a chronic stroke patient
Authors: Julkunen Laura , Tenovuo Olli , Vorobyev Victor , Hiltunen Jaana , Teräs Mika , Jääskeläinen Satu K. , Hämäläinen Heikki
Published: December 2024

Purpose: To study rehabilitation outcome in a chronic visual field defect patient using positron emission tomography (PET) imaging, clinical, and neurophysiological measures.

Methods: A patient with chronic visual field defect was rehabilitated using a computer program over a three-month period. Evaluations of rehabilitation effects were done before and after training, and after a three-month follow-up with perimetry, visual evoked potentials (VEP), subjective questionnaire, and PET activation studies of regional cerebral blood flow (rCBF).

Results: In perimetry, the visual field increased during the training, and the patient also experienced subjective improvement. In VEP, a previously absent P100 component was identified after the training. In PET, increases in rCBF were diffuse immediately after the training, and more occipital after the late follow-up. A significant positive correlation between the increase in rCBF and improvement in clinical measures was found in the lingual gyrus in the contralesional hemisphere.

Conclusions: All clinical measures showed improvement after rehabilitation, and this was maintained during the follow-up. In PET, a more generalized effect, found at the beginning, later concentrated in the occipital cortex. The results suggest that visual training may cause plastic changes in the brain, and that these changes can be detected both with clinical measures and with functional imaging.
The need for randomised treatment studies in neglect	research
Authors: Lincoln N.B. , Bowen A.
Published: December 2024

Purpose: The aim was to review the methodological quality of trials to evaluate rehabilitation for spatial neglect and to determine the overall effectiveness of interventions

Methods: A systematic literature review and meta-analysis were conducted of trials completed by 2005. Trials identified were independently assessed for methodological quality by two reviewers. Outcomes were analysed as the standardised mean difference and 95% confidence intervals with random effects models.

Results: 25 trials of neglect rehabilitation were identified, 12 randomised controlled trials and 13 controlled clinical trials. The methodological quality was generally poor with only 4 trials achieving an A rating, i.e. low risk of selection bias. The immediate effect of cognitive rehabilitation on disability was small, 0.26 [−0.16, 0.67] and neither this nor the persisting effect 0.61 [−0.42, 1.63] was statistically significant. The most frequently used standardised neglect test (number of single letters correctly cancelled) favoured the experimental group 0.58 [0.10, 1.05] but was not significant. When cancellation errors were measured there was a small immediate effect favouring the experimental group, of borderline statistical significance, −0.65 [−1.28, −0.01] p=0.05, and a significant persisting effect −0.76 [−1.39, −0.13] p=0.02. Cognitive rehabilitation also significantly improved immediate (p=001) and persisting (p=0.02) line bisection performance but these findings are based on only four and one study respectively.

Conclusions: The quality of trials identified was poor. Analysis of randomised controlled trials showed some evidence of an effect of intervention on measures of impairment. There was no evidence to support the effects of intervention on measures of disability. Further trials must use methods that reduce bias, have adequate statistical power, and include valid disability outcome measures.
Using limb movements to improve spatial neglect: The role of	functional electrical stimulation
Authors: Eskes Gail A. , Butler Beverly
Published: December 2024

Purpose: Spatial neglect is common after right-hemisphere stroke and has proven resilient to a number of therapeutic interventions. Both active and experimenter-induced passive movements of the left limb in left hemispace have been shown to ameliorate neglect in subsets of patients by improving performance on tasks requiring attention to the left side of space. However, the high incidence of contralesional hemiparesis and poor motor recovery in neglect makes active limb movement therapies applicable to only a small subset of patients. The purpose of our studies was to investigate the effects of passive movements of the left hand by functional electrical stimulation (FES), a common and portable motor rehabilitation technique, on performance in a visual scanning task.

Methods: The effect of FES-induced passive movement on target detection in a visual scanning task was compared to no movement and active movement conditions and also investigated in scanning tasks in both near and far space.

Results: Passive limb movement effects in neglect were variable across and within studies, reference spaces, and individuals, with a subset of positive responders differing from non-responders in regard to constructional deficits and lesion location.

Conclusions: The potential viability of FES as a therapy for neglect deserves further investigation and directions for future research in this area are discussed.