bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet-derived growth factor-producing cells immortalized from	rat mesencephalon with SV40 large T antigen transduced by an AAV vector
Authors: Phillips André W. , Zhang Peisu , Truckenmiller Mary Ellen , Keir Stuart D. , Bouvier Margaret , Tornatore Carlo , Freed William J.
Published: December 2024

Purpose: Adeno-associated virus (AAV) can infect a wide variety of mammalian cell types and is capable of infecting both dividing and non-dividing cell populations. Here we report the construction of a recombinant AAV vector which expresses the SV40 large T protein (AAV-T) and the use of this vector to immortalize primary cells from embryonic rat mesencephalon.

Methods: The AAV-T vector was constructed by introducing the BamH1 fragment of the pCMV/SVE/Neo plasmid containing T antigen and SV40 regulatory elements into the JM48 plasmid containing the inverted terminal repeats of AAV. Neuronal cultures from E-12 rat mesencephalon were grown in defined media supplemented with basic fibroblast growth factor. These cells were infected with the AAV-T vector.

Results: A cell line (designated RMAT) and six subclones were established from these cultures through multiple passages. This cell line was immunoreactive for SV40 large T antigen and the cytoskeletal proteins nestin and vimentin. Morphological differentiation and expression of neurofilament 160 kDa were induced by exposure to dibutyrl cyclic AMP. Immunoassays performed to measure endogenous production of growth factors showed that RMAT cells produced high levels of platelet-derived growth factor (PDGF).

Conclusions: AAV may be a useful vector for the transduction of oncogenes to produce cell lines.
Regeneration of ganglion cell axons into a peripheral nerve graft	alters retinal expression of glial markers and decreases vulnerability to	re-axotomy
Authors: Schuetz Erik , Rose Karin , Thanos Solon
Published: December 2024

Purpose: To compare the effect of cutting the optic nerve versus replacing the cut optic nerve with a peripheral nerve (PN) graft on retinal glial markers, and to determine whether the PN graft can stabilize regenerating retinal ganglion cells (RGCs), thus preventing their death following re-axotomy.

Methods: Retinas harvested after ganglion cell regeneration into a sciatic nerve graft were compared to untreated control retinas and retinas obtained following optic nerve axotomy. Glial-specific proteins such as glial fibrillary acidic protein (GFAP), Bcl-2 and complement-3 receptor (Ox-42) were examined using immunohistochemistry. Ganglion cells that survived the second axotomy were quantified on retinal flat mounts by retrograde labeling from the graft.

Results: GFAP expression in astrocytes and Muller cells was elevated in axotomized retinas when compared to controls, and an additional up-regulation in Muller cells was found in retinas following ganglion cell regeneration. Increased GFAP expression in retinas containing regenerated neurons was accompanied by increased Bcl-2 expression with latter being confined to Muller cells. Moreover, re-axotomy of the regenerated axons within the graft did not result in significant retrograde degeneration of RGCs within 28 days.

Conclusions: The data suggest that the graft stabilizes the regenerating RGCs to an extent reminiscent of peripheral neurons, a process that may involve the interaction between neuronal and glial elements.
Changes in protein levels of elongation factors, eEF1A-1 and	eEF1A-2/S1, in long-term denervated rat muscle
Authors: Khalyfa Abdelnaby , Carlson Bruce M. , Dedkov Eduard I. , Wang Eugenia
Published: December 2024

Purpose: This study was designed to determine whether the quantitative relationship between the levels of the eEF1A-1(developmental) and eEF1A-2/S1 (adult) isoforms of peptide elongation factor remains stable after denervation of skeletal muscle or whether in response to denervation the relative amount of the developmental form would increase. In normal postnatal rat muscle, eEF1A-2/S1 is the dominant form represented, and levels of eEF1A-1 are extremely low.

Methods: One hind limb in young adult rats was permanently denervated. Denervated and corresponding contralateral control muscles were removed for biochemical and morphological analysis from 2 days to 25 months after denervation.

Results: By one month after denervation, relative levels of eEF1A-1 rose dramatically in relation to those of eEF1A-2/S1, and they remained high throughout the remainder of the 25-month denervation period. Ultrastructural analysis showed a complex mix of muscle fiber atrophy, dying muscle nuclei and muscle fibers, and newly forming muscle fibers in the same tissue.

Conclusions: As during muscle regeneration, levels of the developmental eEF1A-1 isoform of peptide elongation factor greatly increased relative to those of the adult eEF1A-2/S1 adult isoform following denervation in rat muscles. However, in contrast to regeneration, the elevated level of eEF1A-1 did not return to the basal minimal level. Since switching from eEF1A-1 to eEF1A-2/S1 is an indicator that terminal differentiated is completed, the failure of eEF1A-1 to return to basal level may be indicative of the persistence of an unstable tissue environment that includes muscle fiber atrophy, degeneration and neomyogenesis. The specific cellular basis for the increase in eEF1A-1 could not be determined from this study.
Changes in motor system function and recovery after stroke
Authors: Cramer Steven C.
Published: December 2024

Motor system impairments are common after stroke and are a major contributor to disability after stroke. Most patients show improvement in the weeks-months following a stroke. Understanding the neurobiological underpinnings of these behavioral gains may be useful for refining treatments that aim to improve outcome and reduce disability. A number of brain mapping studies have examined how stroke affects motor system function. Numerous changes have been identified in this setting and are reviewed herein, including reduced laterality, widespread changes across a distributed sensorimotor network, and a change in the site and size of key activation foci. Some of these changes have been found to correlate with features of injury, behavior, or treatment-induced behavioral gains. A current challenge is to extend these findings to improve clinical decision making.
Constraint-induced movement therapy for chronic stroke hemiparesis	and other disabilities
Authors: Mark Victor W. , Taub Edward
Published: December 2024

Constraint-Induced Movement Therapy (CI therapy) refers to a family of treatments for motor disability that combines constraint of movement, massed practice, and shaping of behavior to improve the amount of use of the targeted limb. CI therapy has controlled evidence for efficacy that supports its benefit for patients with chronic disability following central nervous system injury, regardless of their age or the interval since illness onset. Furthermore, the benefits transfer to real-world measures of limb use. Significant functional improvement may occur even after the patient has been treated with conventional physical therapy. In this paper we review the evidence for the efficacy of CI therapy, particularly for chronic stroke hemiparesis, but also for diverse other chronic disabling illnesses, including non-motor disorders such as phantom limb pain and aphasia. The adaptation of the therapy to the stroke clinic is described, along with a review of the neurophysiologic mechanisms that are postulated to underlie the treatment benefit (overcoming learned nonuse, plastic brain reorganization). Critical to the success of CI therapy is its modification according to disease factors, economic considerations, limitations of the practice setting, and the cognitive and physical status of the patient. We conclude by recommending future areas for research on CI therapy.
Cortical reorganization – effects of intensive therapy
Authors: Nelles Gereon
Published: December 2024

Recovery from hemiparesis after stroke largely depends on widespread functional and structural neuronal plasticity. Based on animal studies of rehabilitative and pharmacological interventions on recovery, recent neuroscientific findings suggest that new rehabilitative interventions may also have benefits by modulating neuroplastic mechanisms in stroke patients. Neurofunctional imaging methods such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) as well as transcranial magnetic stimulation (TMS) now permit direct studies of training-induced plasticity in stroke patients. Prospectively conducted studies using these techniques have investigated how plasticity relates to recovery of motor function and how intensive training modulates cortical reorganization. Despite technical and methodological differences, consistent neuroanatomic findings on training-induced reorganization of the motor system have been reported. These discoveries have important implications for the future development of neurorehabilitative training methods. With continuously improving methods to study cortical reorganization and over 100 randomized clinical trials on stroke rehabilitation published during the past five years, this promises to be an exciting time in stroke rehabilitation research.
Functional and cellular effects of environmental enrichment after	experimental brain infarcts
Authors: Johansson Barbro B.
Published: December 2024

Our genes interact with environmental stimuli throughout our lives. The attitude and reaction to an acute cerebral trauma or stroke, as well as the pre-lesion life event and activities, can influence functional outcome. Although difficult to separate in adult human beings, genetic and environmental factors can be selectively evaluated in animal studies. Post- ischemic housing in an enriched environment, i.e. larger cages which allow both social interaction and various activities improves functional outcome, modifies gene activation, and increases dendrite branching and number of dendritic spines in pyramidal neurons in layers II-III in the contra-lateral cortex. Furthermore, it alters lesion-induced progenitor cell differentiation and interacts with neocortical transplantation, drug treatment and training. It is proposed that the interaction between environment and specific treatment needs more clinical attention, and that a general stimulating and positive environment is the optimal base for specific interventions in neurological rehabilitation.
Bromodeoxyuridine increases multipotency of human bone	marrow-derived stem cells
Authors: Qu Ting Yu , Dong Xia Jing , Sugaya Ikuko , Vaghani Ankur , Pulido Jose , Sugaya Kiminobu
Published: December 2024

Purpose: Recent reports show that marrow derived mesenchymal stem cells (MeSCs) may have the ability to differentiate into diverse cell types unrelated to their phenotypical embryonic origin, including neural cells. While demonstrated "in vitro" and neonatally, efforts to demonstrate this ability in adult animal brains have had limited success. If it can be shown that human MeSC (HMeSC) can differentiate into neural cells in adult brain, it would open up the possibility that HMeSCs may be of potential therapeutic use in cell replacement therapies for neurological diseases. Here, we demonstrate that adult HMeSCs treated with 5-bromo-2-deoxyuridine (BrdU) for 3 weeks develop the capability to differentiate into neural and retinal cells when provided the appropriate lineage specific differentiation signals in vitro and in adult animals. HMeSC without BrdU treatment did not differentiate into neurons in vitro or adult animal or retinal cells in adult animal.

Methods: MeSCs isolated from adult human bone marrow were treated with BrdU (3 μM) for 3 weeks and then subjected to differentiation conditions both in vitro and in vivo.

Results: BrdU pretreated HMeSCs express neuronal and glial markers after co-culture with differentiated human neural stem cells and after transplantation into the adult rat brain. HMeSCs pretreated with BrdU and transforming growth factor-β3 express a photoreceptor marker after transplantation into the adult rat vitreous.

Conclusions: These results suggest that BrdU treatment may increase the multipotency of HMeSCs for possible use in autologous cell therapies for neurological and opthamological diseases.
Post-training stimulation of the basolateral amygdala improves	spatial learning in rats with lesion of the fimbria-fornix
Authors: Almaguer William , Capdevila Vladimir , Ramírez Magaly , Vallejo Araceli , Rosillo Juan C. , Bergado Jorge A.
Published: December 2024

Purpose: To evaluate the capacity of amygdala stimulation to improve neural plasticity in animals bearing lesions of the fimbria-fornix (FF) system.

Methods: The animals were lesioned under narcosis (chloral hydrate, 420 mg/kg ip.) using a bilateral transection of the FF procedure. During the same surgery some animals were implanted with an electrode in the right basolateral amygdala (BLA) to allow the electrical stimulation of this structure. Training was carried out one week after surgery using a Morris water maze. Animals were trained in four consecutive days (8 trials/day) in the non-visible platform condition except in the fourth day in which only 4 trials were performed followed by a probe trial in which the escape platform was removed. On day 5 of training 8 trials with visible platform were performed. After each of the first 3 training days one group of animals received trains of electrical stimulation to the BLA, while control groups were not stimulated. A group of non-lesioned animals served as control. The location of the electrode was confirmed histologically after the end of the experiments.

Results: The learning capacity of the lesioned animals was improved by the electrical stimulation of the amygdala. The latency to find the submerged platform within this group approaches that of the non lesioned animals in the course of training (2-way ANOVA with repeated measures), while other lesioned animals continued to show severely impaired learning abilities.

Conclusions: This is the first evidence that stimulating the BLA can positively influence the learning abilities of lesioned animals. Further experiments should contribute to improve the stimulation paradigms to make it more effective, if possible.
FK506 and anti-CD40 ligand in peripheral nerve	allotransplantation
Authors: Brenner Michael J. , Mackinnon Susan E. , Rickman Susan R. , Jaramillo Andrés , Tung Thomas H.H. , Hunter Daniel A. , Mohanakumar T.
Published: December 2024

Purpose: Immunomodulatory agents are often combined in organ transplantation to minimize toxicity and enhance therapeutic effect. We hypothesized that combining low-dose FK506 with anti-CD40 Ligand (anti-CD40L mAb) would enhance regeneration through peripheral nerve allografts while preserving immune unresponsiveness.

Methods: Eighty Balb/cJ mice underwent tibial nerve grafting and were randomized to 10 groups treated with combinations of anti-CD40L mAb therapy, low-dose FK506 (0.5 mg/kg/day), high-dose FK506 (2 mg/kg/day), and high-dose cyclosporine (25 mg/kg/day). At 3 weeks, histomorphometry and cytokine secretion assays were performed.

Results: Animals receiving low-dose FK506 with anti-CD40L mAb exhibited robust nerve regeneration comparable to the isograft and high-dose FK506 allograft groups. Nerve density was significantly increased in the low-dose FK506 with anti-CD40L mAb group compared to animals receiving anti-CD40L mAb alone (p < 0.05). Combining anti-CD40L mAb with high dose cyclosporine decreased nerve fiber counts, nerve density, and percent nerve (p < 0.05). Interferon-γ production was markedly elevated in untreated allografts compared to all other treatment groups (p < 0.05). Cytokine secretion was intermediate in the low-dose FK506 alone group and suppressed in all remaining groups.

Conclusion: When combined with anti-CD40L mAb, low-dose FK506 enhances nerve regeneration without disrupting immune unresponsiveness.
Ischemic lesion volume correlates with long-term functional	outcome and quality of life of middle cerebral artery stroke survivors
Authors: Schiemanck S.K. , Post M.W.M. , Kwakkel G. , Witkamp Th.D. , Kappelle L.J. , Prevo A.J.H.
Published: December 2024

Purpose: Previous studies investigating relationships between stroke lesion volume and outcome were restricted to short follow-up periods (3–6 months) and outcome measures of stroke severity and activities only, whereas functional improvement has been found to extend far beyond six months. Therefore, this study investigated relationships between infarct volume and a broad range of outcomes of stroke survivors at a long follow-up period.

Methods: Correlations between lesion volumes (determined by conventional MRI scans in the second week post-stroke) and outcomes after one year of 75 first-ever ischemic stroke survivors were investigated.

Results: Moderate Spearman Rank correlation coefficients were found between lesion volume and motor impairment (Motricity Index (MI): −0.43, p < 0.01; Fugl Meyer Motor Assessment Scale (FM): −0.43; p < 0.01). Correlation coefficients with activities of daily living were moderate but low associated with Barthel Index (r $_s$ = 0.30; p < 0.01), modified Rankin Scale (r $_s$ = 0.39; p < 0.01) and Frenchay Activities Index (r $_s$ = −0.35; p < 0.01). Lesion volume had a significant but low association (r $_s$ = 0.27; p = 0.02) with patient's health status measured with Sickness Impact Profile 68 (SIP68)) and a moderate correlation with well-being assessed with Life Satisfaction Questionnaire (LSQ; r $_s$ = −0.45; p < 0.01). Found correlation coefficients were slightly stronger after correction for mixed (cortical/subcortical) and purely subcortical lesion location.

Conclusions: It can be concluded that infarct volume moderately correlates with long-term motor impairment, functional outcome and quality of life of patients surviving stroke.
The NMDA receptor antagonist CGS 19755 disrupts recovery following	cerebellar lesions
Authors: Federico Francesca , Leggio Maria G. , Mandolesi Laura , Petrosini Laura
Published: December 2024

Purpose: To test whether activation of NMDA receptors is required for the maintenance of the posture and motor behavior recovered from cerebellar lesions, an NMDA antagonist (CGS 19755) was systemically administered to totally or partially cerebellectomized rats.

Methods: Three groups of animals were tested: rats that had undergone a total cerebellectomy four months before drug administration; rats that had undergone a right hemicerebellectomy four months before drug administration; intact control animals.

Results: Under drug action in the control animals the postural pattern was slightly influenced, showing a light worsening, and motor skills requiring coordinated motor performance and subtle balance control were markedly worsened. Conversely, in the lesioned groups the cerebellar symptomatology dramatically worsened, and both groups of animals looked like they had just been operated, exhibiting the whole repertoire of postural and motor behaviors of cerebellar origin. In particular, limb hyperflexion, wide-based locomotion and the tendency to side falls were prevalent in the cerebellectomized animals, while tremor and body tilt were prevalent in the hemicerebellectomized group.

Conclusion: The reappearance of severe postural and motor symptomatology has to be interpreted as a "decompensation" evoked by the NMDA-receptor antagonist, suggesting the involvement of NMDA receptors in the maintenance of compensation of disturbances of cerebellar origin.
Gene expression profiling in the hippocampus of rats subjected to	focal cerebral ischemia and enriched environment housing
Authors: Sonninen Riitta , Virtanen Tiina , Sivenius Juhani , Jolkkonen Jukka
Published: December 2024

Purpose: Enriched environment housing enhances brain plasticity and improves recovery of impaired sensorimotor and cognitive functions of rats subjected to transient middle cerebral artery occlusion (MCAO). The present study applied microarray technique to investigate the molecular basis through which enriched environment might improve spatial learning in MCAO rats.

Methods: MCAO rats were housed in enriched environment or in standard single cages, and sham-operated rats were housed in standard single cages. Spatial learning was assessed using the Morris water-maze on postoperative days 22 to 24. Total RNA from the ipsilateral hippocampus was extracted for microarray analysis after the follow-up period.

Results: Water-maze performance on postoperative days 22 to 24 showed that rats subjected to transient MCAO were impaired in the hippocampus-dependent Morris water-maze test. Enriched environment housing reversed the spatial learning impairment on postoperative day 23. Gene expression in the hippocampus was not affected by MCAO or following enriched environment housing.

Conclusion: Spatial learning impairment following transient MCAO in rats and cognitive improvement following housing in enriched environment may not be related to altered hippocampal gene expression.
Statin-mediated protective effects in the central nervous system:	General mechanisms and putative role of stress proteins
Authors: Schmeer Christian , Kretz Alexandra , Isenmann Stefan
Published: December 2024

Purpose: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. This review, focused on recent experimental and clinical data, summarizes general mechanisms of statin actions underlying neuroprotective effects in the central nervous system (CNS) and presents evidence for putative mechanisms involving heat shock proteins and the survival-related PI-3K/Akt pathway that may be beneficial for the treatment of neurological disorders.

Methods: We carried out a medline search on statin actions, with respect to biochemical pathways and signal transduction on the one hand, and clinical studies in neurologic and retinal diseases on the other hand. Novel experimental data obtained in a rat model of axonal CNS injury were also included.

Results: Statins exert multiple effects on endothelial function, cell proliferation, inflammatory response, immunological reactions, platelet function, and lipid oxidation. These "pleiotropic actions" are independent of cholesterol lowering and appear to be beneficial in the context of brain injury. Several mechanisms of statin actions underlying neuroprotective effects may also involve heat shock proteins and the survival-related PI-3K/Akt pathway.

Conclusions: Available data suggest that statins may be of potential therapeutic use in a variety of diseases of the CNS including ischemic stroke, Alzheimer's disease, multiple sclerosis and some forms of retinal and eye diseases. Before general recommendations can be made and specific therapeutic approaches can be developed, more reliable clinical data and studies are required, and possible side effects must be carefully evaluated.
Combination of TMS and fMRI reveals a specific pattern of	reorganization in M1 in patients after complete spinal cord injury
Authors: Lotze M. , Laubis-Herrmann U. , Topka H.
Published: December 2024

Purpose: After a spinal cord injury (SCI), which was complete, deafferentation of the body representation caudal to the lesion height results in drastic changes in the cortical representation. The underlaying processes are poorly understood.

Methods: We investigated cortical representation sites of upper limb muscles using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in five patients suffering from thoracic complete SCI and one with an incomplete SCI in the height of L1.

Results: In comparison to healthy controls fMRI demonstrated a displacement of elbow movement representations in the precentral gyrus in patients with complete SCI into the direction of the deafferented cortical thoracic representation. Changes increased with time after the incidence of SCI. TMS revealed reduced excitability and prolonged silent periods for muscles more distant to the deafferented area.

Conclusions: Whereas fMRI demonstrated changes in representation sites adjacent to the deafferented area, TMS excitability changes were also observed more distant to the deafferented area and silent periods were prolonged in comparison to healthy controls. TMS changes might depend on both: the distance to the deafferented area and the time of persistence of deafferentation.
Effect of the knee joint tracking training in closed kinetic chain	condition for stroke patients
Authors: Chung Yi-Jung , Cho Sang-Hyun , Lee Young-Hee
Published: December 2024

Purposes: This study tested the hypothesis that our method of knee-joint-tracking training for stroke patients induces significant motor learning effects, and the findings were compared with those of previous studies.

Methods: Six stroke patients and six age-matched healthy controls were recruited. The tracking task involved following computer-generated sine waves of changing frequency (0.2, 0.3, or 0.4 Hz) for each repeating cycle with a plot of the knee-joint angle on a computer monitor as closely as possible. The closed-kinetic chain set involved standing with both hands placed on a support table, with one foot placed on a wooden box and the other foot placed on a digital body-weight scale. The sessions in this study were performed in the following sequence: practice, pretest evaluation, 4 weeks of training, and posttraining evaluation. The tracking performance was evaluated with the accuracy index (AI) score.

Results: Tracking training produced a significant improvement not only in the motor-function scores but also in the AI score of the stroke-patient group. The improvement in their AI did not differ significantly from that of the control group.

Conclusions: Our tracking protocol exerted a significant training effect in stroke patients, and the AI improvement was greater than that induced by the most recent protocol. This training will enhance motor skill acquisition and possibly contribute to cortical reorganization.
What do eye-fixation patterns tell us about unilateral spatial	neglect?
Authors: Ishiai Sumio
Published: December 2024

Purpose: Eye-fixation patterns, which include ocular searching and fixation, may change with tasks, stimuli, and instructions. This article reviews our studies over 18 years on eye-fixation patterns of neglect patients and aims to elucidate the visuospatial processing of unilateral spatial neglect.

Methods: We recorded eye-fixation patterns when patients with neglect bisected a line in various conditions.

Results: Patients with neglect rarely searched to the left side when bisecting a line of the ordinary length (e.g., 200 mm). They persisted in fixating a right-side point, at which they later marked the subjective midpoint. They made no effective comparison between the leftward and rightward extents not only for a whole line but also for its explored right segment. Where they 'favored' to fixate as the subjective midpoint depended strongly upon the location of the right endpoint in space. Their representational image of a line was also estimated with modified line bisection tasks performed on a touch-panel display.

Conclusions: For patients with neglect, the representational image of a line may be formed on the basis of the attended segment between the right endpoint and the favored point of fixation. The line bisection task, if combined with recording of eye-fixation, would further contribute to elucidation of the mechanisms underlying neglect.
Postural disorders and spatial neglect in stroke patients: A	strong association
Authors: Pérennou Dominic
Published: December 2024

Purpose: In this paper we analyse the arguments for a strong association between spatial neglect and postural disorders and attempt to better understand the mechanisms which underlie that.

Methods: We first provide a general overview of the available tools for a rational assessment of postural control in a clinical context. We then analyse the arguments in favour of a close relationship, although not necessarily causal, between spatial neglect and: 1) body orientation with respect to gravity (including verticality perception i.e. the visual vertical, the haptic vertical, and the postural vertical); 2) body stabilisation with respect to the base of support; 3) posturographic features of stroke patients; 4) and finally their postural disability in daily life. This second part of the paper is based both on the literature review and on results of our current research.

Results: Neglect patients show a dramatic postural disability, due both to problems in body orientation with respect to gravity and to problems in body stabilisation. It might be that these problems are partly caused by a neglect phenomenon bearing on graviceptive (somaesthetic > vestibular) and visual information serving postural control. This could correspond to a kind of postural neglect involving both the bodily and nonbodily domains of spatial neglect. The existence of distorsion(s) in the body scheme are also probably involved, especially to explain the weight-bearing asymmetry in standing, and probably an impaired multisegmental postural coordination leading to an impaired body stabilisation.

Conclusion: The present paper explains why neglect patients show longer/worse recovery of postural-walking autonomy than other stroke patients.
Supraspinal inputs reduce corticomotor excitability during passive	movement: Evidence from a pure sensory stroke
Authors: Edwards D.J. , Mastaglia F.L. , Byrnes M.L. , Fregni F. , Pascual-Leone A. , Thickbroom G.W.
Published: December 2024

Corticomotor excitability is reduced during rhythmic passive movement compared to rest, but it is not known whether the mechanism is purely segmental or includes a supraspinal pathway. To determine how interruption of sensory projections at a supraspinal level affects corticomotor excitability during passive movement, we measured the amplitude of motor evoked potential (MEP) during 1 Hz cyclic index finger movements in a patient with a brainstem and thalamus lesion that resulted in a pure sensory stroke. Measurements of MEP amplitude and proprioception were made 14 and 64 days post-stroke. In the first study, when subjective position sense was reduced for the index finger, MEP amplitude was significantly increased during passive movement compared to rest (4.6 ± 0.2 SEM mV vs. 4.0 ± 0.2 mV; p=0.0281). However in the second study, when position sense had returned to normal, MEP amplitude was significantly reduced during movement compared to rest (6.2 ± 0.3 mV vs. 6.6 ± 0.1 mV; p=0.0224). These observations provide evidence that supraspinal sensory pathways are involved in reducing corticomotor excitability during rhythmic passive movement.
MRI infarction load and CI therapy outcomes for chronic	post-stroke hemiparesis
Authors: Mark Victor W. , Taub Edward , Perkins Christi , Gauthier Lynne , Uswatte Gitendra
Published: December 2024

Purpose: To evaluate the effect of total cerebral infarction volume on motor status and treatment responses to Constraint-Induced Movement therapy (CI therapy) in patients with chronic post-stroke hemiparesis and limb nonuse. In most studies of clinical-radiological correspondences, infarct volume has been found to predict clinical status.

Methods: 60 adult patients who met inclusion criteria for CI therapy underwent standard structural brain MRI around the time of treatment. We tested whether the total volume of infarcted tissue predicted pre-treatment values and pre- to post-treatment changes on standard assessments of laboratory- and real-world-based upper extremity movement.

Results: The patients significantly improved from baseline clinical motor measures after CI therapy. The range of infarction volumes was comparable to those of other stroke studies. In contrast, total infarction volume was not correlated with any of the motor measures. The absence of correlation was maintained even when evaluating only patients with either unilateral or solitary cerebral infarctions, or with respect to severity of baseline motor impairment or variations in the forms of therapy.

Conclusion: The findings suggest that certain standard motor measures in chronic hemiparetic stroke (limb movement in the laboratory, limb use in the life situation, changes in these measures following efficacious CI therapy) are insensitive to infarction load. Our findings are consistent with the hypothesis that plastic brain reorganization after stroke attenuates the effect of infarct volume on purposive limb movement. However, we cannot exclude the possibilities that the specific methods we used to assess upper limb status may be generally insensitive to infarction load, or that the stringent inclusion criteria for this research precluded detecting an effect of infarction load. Further study to evaluate these relationships in the acute-subacute stroke phases and among patients with more severe motor deficits would help to clarify the basis for the lack of an infarction load effect.
A special role for binocular visual input during development and	as a component of occlusion therapy for treatment of amblyopia
Authors: Mitchell Donald E.
Published: December 2024

Purpose: To review work on animal models of deprivation amblyopia that points to a special role for binocular visual input in the development of spatial vision and as a component of occlusion (patching) therapy for amblyopia.

Methods: The studies reviewed employ behavioural methods to measure the effects of various early experiential manipulations on the development of the visual acuity of the two eyes.

Results: Short periods of concordant binocular input, if continuous, can offset much longer daily periods of monocular deprivation to allow the development of normal visual acuity in both eyes. It appears that the visual system does not weigh all visual input equally in terms of its ability to impact on the development of vision but instead places greater weight on concordant binocular exposure. Experimental models of patching therapy for amblyopia imposed on animals in which amblyopia had been induced by a prior period of early monocular deprivation, indicate that the benefits of patching therapy may be only temporary and decline rapidly after patching is discontinued. However, when combined with critical amounts of binocular visual input each day, the benefits of patching can be both heightened and made permanent.

Conclusions: Taken together with demonstrations of retained binocular connections in the visual cortex of monocularly deprived animals, a strong argument is made for inclusion of specific training of stereoscopic vision for part of the daily periods of binocular exposure that should be incorporated as part of any patching protocol for amblyopia.
Functional rehabilitation of partial cortical blindness?
Authors: Stoerig Petra
Published: December 2024

The current doctrine regards fields of partial cortical blindness as permanent once a temporally restricted window for spontaneous recovery has passed. Accordingly, neuropsychological rehabilitation mainly applies compensatory procedures that train patients to make better use of their sighted field. The more ambitious goal of functional recovery depends on the survival of pathways that continue to transmit retinal information from the blind field. Although wide-spread antero- and retrograde degeneration follows lesions that destroy or denervate the primary visual cortex and cause partial cortical blindness, several retinofugal pathways survive in cats, monkeys, and humans. In all three species, they subserve a variety of visual functions which develop and improve with practice. Post lesion plasticity is greater when the lesion occurs early in life, but changes in behavioural performance and brain responses have also been demonstrated in late lesion subjects. Although the extent of functional improvement is variable, and the most effective approaches still need to be established across cohorts, the evidence for perceptual learning in fields of cortical blindness indicates that the visual processes mediated by the surviving parts of the visual system can be harnessed to improve functional outcome.
Emerging syphilitic optic neuropathy: Critical review and	recommendations
Authors: Prokosch Verena , Thanos Solon
Published: December 2024

Background: Infection with Treponema pallidum causes multiorgan manifestations including isolated optic nerve involvement at any stage of the disease. This is of particular interest for resulting in severe visual impairment, which is reversible if treated adequately.

Purpose: To review clinical and diagnostic findings in patients with optic nerve affection in neurosyphilis and to focus on the visual outcome after administering adjunctive cortisone to the standard therapy regimes with penicillin G.

Methods/Patients: The review is based on a retrospective case serial of 4 patients (three males: mean age 40years, range 37–42 years; one female: mean age 62years) with optic nerve involvement in neurosyphilis treated in our hospital, and on a literature review of recent publications. Patients were treated with systemic penicillin either with or without adjunctive cortisone. The major outcome measure of therapy was improvement of visual acuity.

Results: Visual outcome in our case serial showed total restoration if cortisone was also administered. The bibliographic survey, which was based on 60 patients, also revealed a better improvement of vision when antibiotic medication was combined with cortisone.

Conclusions: The data show that the causal therapy of choice is undoubtedly penicillin G, with adjunctive steroids playing a crucial role in improvement of optic nerve functional outcome. Physicians should consider the use of cortisone in SON whenever clinically harmless, although prospective randomized multicenter studies are required to support this recommendation.
Protective effects of gastrodia elata on	aluminium-chloride-induced learning impairments and alterations of amino acid	neurotransmitter release in adult rats
Authors: Shuchang He , Qiao Niu , Piye Niu , Mingwei He , Xiaoshu Sun , Feng Shao , Sheng Wang , Opler Mark
Published: December 2024

Purpose: High brain levels of aluminum (Al) can be neurotoxic and cause learning and memory deficits. Gastrodia elata (GE) is a Chinese herb widely used for improving mental function in traditional Chinese medicine. We measured changes in Al-induced neurotransmitter alteration and performance on a learning and memory task to elucidate the mechanism of Al toxicity and to assess whether these alterations could be attenuated by GE.

Methods: Thirty-six adult, male rats were randomly divided into six groups. Four Al-exposed groups were given aluminum chloride at 5 mg/kg/day or 10 mg/kg/day (i.p.) for two months, with two of these groups (one for each dose of Al) receiving GE (0.4 g/kg, via oral intubation, with the GE powder mixed in the drinking water) while the other two groups received vehicle. A GE control group was given injections of saline plus GE and a saline control group was given injections of saline and with 3 injection days and one day off. A step-down test was used to measure learning and memory ability. Al concentrations in the neocortex were assayed with a graphite furnace atomic absorption spectrophotometer. Amino acid neurotransmitter levels in the neocortex were determined by high performance liquid chromatogram-fluorescence.

Results: Al-exposed rats showed impaired learning and memory ability as indicated by shorter step down latency and more retention errors. Cortical concentrations (mean ± SEM) of Al were: 56.22 ± 34.10 ng/g (wet weight) in the Saline control group; 172.87 ± 111.06 in the 5 mg/kg/dayAl group; 289.15 ± 102.55 in the 10 mg Al group; 74.98 ± 19.00 in the GE control group; 232.55 ± 35.74 in 5 mg Al+GE group; and 291.35 98.38 in 10 mg Al+GE group respectively. Al exposure produced a significant increase in cortical GABA levels. Gastrodia elata reduced learning and memory deficits without affecting brain Al levels.

Conclusions: Rats exposed to AlCl $_{3}$ suffer from deficits in learning and memory, accompanied by increases in GABA levels in the neocortex. Gastrodia elata is effective in improving memory functions and normalizing GABA levels.
Cerebellar control of cortico-striatal LTD
Authors: Rossi Silvia , Mataluni Giorgia , De Bartolo Paola , Prosperetti Chiara , Foti Francesca , De Chiara Valentina , Musella Alessandra , Mandolesi Laura , Bernardi Giorgio , Centonze Diego , Petrosini Laura
Published: December 2024

Purpose: Recent anatomical studies showed the presence of cerebellar and basal ganglia connections. It is thus conceivable that the cerebellum may influence the striatal synaptic transmission in general, and synaptic plasticity in particular.

Methods: In the present neurophysiological investigation in brain slices, we studied striatal long-term depression (LTD), a crucial form of synaptic plasticity involved in motor learning after cerebellar lesions in rats.

Results: Striatal LTD was fully abolished in the left striatum of rats with right hemicerebellectomy recorded 3 and 7 days following surgery, when the motor deficits were at their peak. Fifteen days after the hemicerebellectomy, rats had partially compensated their motor deficits and high-frequency stimulation of excitatory synapses in the left striatum was able to induce a stable LTD. Striatal plasticity was conversely normal ipsilaterally to cerebellar lesions, as well as in the right and left striatum of sham-operated animals.

Conclusions: These data show that the cerebellum controls striatal synaptic plasticity, supporting the notion that the two structures operate in conjunction during motor learning.
Improved sensorimotor function by rolipram following focal	cerebral ischemia in rats
Authors: Hätinen Sonja , Sairanen Mikko , Sirviö Jouni , Jolkkonen Jukka
Published: December 2024

Purpose: Rolipram, a specific phosphodiesterase 4 inhibitor (PDE4), is suggested to facilitate functional recovery following brain injury by activation of cAMP/CREB pathway. We examined the effect of rolipram on sensorimotor recovery in rats following transient occlusion of the middle cerebral artery (MCAO).

Methods: Rats were subjected to transient MCAO for 2 h. Rolipram was administered at a dose of 0.1 or 1 mg/kg (i.p., twice a day, for 13 days) starting administration on postoperative day 2. Sensorimotor outcome was assessed using limb-placing, beam-walking and cylinder tests at baseline and 7, 14, and 21 days after MCAO.

Results: Rolipram decreased locomotor activity and rearing, produced atypical head twitches, and possible hyperalgesia immediately after treatments, which were all considered as acute side effects. The analysis of hindlimb function utilizing beam-walking tests showed that overall performance was impaired in MCAO vehicle rats (p < 0.01) and MCAO rats treated with rolipram, at a dose of 0.1 mg/kg (p < 0.01), compared to sham-operated rats. Interestingly, MCAO rats treated with rolipram at a dose of 1.0 mg/kg had significantly fewer slips when traversing an elevated beam than those treated with a dose of 0.1 mg/kg (p < 0.05) indicating improved sensorimotor function. More importantly, hindlimb function at the higher rolipram dose was not different from sham-operated rats after cessation of drug treatment at day 21. There was a significant group effect (p < 0.001) in the cylinder test, however, this was due to the decreased use of the impaired forelimb in MCAO rats compared to sham-operated rats at day 7, 14 and 21. In addition, MCAO rats treated with rolipram seemed to use their impaired forelimbs less compared to MCAO controls. Limb-placing performance was severely impaired but not different among MCAO rats.

Conclusions: The present data suggest that rolipram provides some improvement in sensorimotor recovery in MCAO rats possibly by augmenting cAMP/CREB signalling, but this is masked by its side effects.
Cell adhesion molecules of the immunoglobulin superfamily in	axonal regeneration and neural repair
Authors: Zhang Yi , Yeh John , Richardson Peter M. , Bo Xuenong
Published: December 2024

Cell adhesion molecules (CAMs) play important roles in cell-cell and cell-extracellular matrix interactions in both mature and developing nervous system. During development, they are involved in cell migration, axon guidance, target recognition, and synapse formation; while in the mature nervous system, they maintain synaptic connections, cell-cell contacts, and neuron-glial interactions. Injuries to the nervous systems break the stable state of the tissues and the repair of damaged tissues and regeneration of axons require the participation of CAMs both as adhesion molecules and as signal transduction molecules. One group of the well-studied CAMs in the nervous system is the immunoglobulin superfamily including L1 and neural cell adhesion molecule (NCAM). This review will be focussed on the involvement of L1, NCAM, and polysialylated NCAM in neural repair and axon regeneration after nerve injury and their potential applications in the treatment of CNS injury.
Dimethyl sulfoxide provides neuroprotection in a traumatic brain	injury model
Authors: Di Giorgio Anthony M. , Hou Yongjin , Zhao Xueren , Zhang Bin , Lyeth Bruce G. , Russell Michael J.
Published: December 2024

Purpose: The objective of this study was to evaluate the neuroprotective potential of the antioxidant, curcumin compared to α-tocopherol in a rat model of traumatic brain injury (TBI).

Methods: Male Sprague-Dawley rats were administered curcumin (3, 30, 300 mg/kg), α-tocopherol (100 mg/kg), DMSO vehicle, or saline, 30 min prior to and 30 and 90 min after moderate lateral fluid percussion TBI. Rats were euthanized at 24 hours after injury and coronal brain sections were stained with Fluoro-Jade to identify degenerating neurons. Degenerating neurons in the CA2-3 sector of the dorsal hippocampus were quantified in 10 sections spaced 300 μm apart in each rat.

Results: One way ANOVA revealed a significant difference (p = 0.01) between groups. The curcumin, α-tocopherol, and DMSO groups had significantly reduced numbers of degenerating neurons compared to the saline-treated group. No significant differences were observed between any of the drug treatment groups or the DMSO group.

Conclusions: Since protection in the DMSO vehicle group was equal to that of the experimental groups, no conclusions about neuroprotection regarding α-tocopherol or curcumin can be made from this study. The results suggest that DMSO may be acting as an overriding neuroprotectant in this experiment. We conclude that DMSO is a viable neuroprotective agent against secondary cell death in TBI.
Don't fence me in: Harnessing the beneficial roles of astrocytes	for spinal cord repair
Authors: White Robin E. , Jakeman Lyn B.
Published: December 2024

Astrocytes comprise a heterogeneous cell population that plays a complex role in repair after spinal cord injury. Reactive astrocytes are major contributors to the glial scar that is a physical and chemical barrier to axonal regeneration. Yet, consistent with a supportive role in development, astrocytes secrete neurotrophic factors and protect neurons and glia spared by the injury. In development and after injury, local cues are modulators of astrocyte phenotype and function. When multipotent cells are transplanted into the injured spinal cord, they differentiate into astrocytes and other glial cells as opposed to neurons, which is commonly viewed as a challenge to be overcome in developing stem cell technology. However, several examples show that astrocytes provide support and guidance for axonal growth and aid in improving functional recovery after spinal cord injury. Notably, transplantation of astrocytes of a developmentally immature phenotype promotes tissue sparing and axonal regeneration. Furthermore, interventions that enhance endogenous astrocyte migration or reinvasion of the injury site result in greater axonal growth. These studies demonstrate that astrocytes are dynamic, diverse cells that have the capacity to promote axon growth after injury. The ability of astrocytes to be supportive of recovery should be exploited in devising regenerative strategies.