bluuebunny/crossref_metadata_2025_split 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.
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.