bluuebunny/crossref_metadata_2025 huggingface dataset:
Axonal regeneration by chronically injured supraspinal neurons can be enhanced by exposure to insulin-like growth factor, basic fibroblast growth factor or transforming growth factor beta
Authors: Houle John D. , Ye Jian Hui , Kane Cynthia J.M.
Published: December 2019

To test whether known growth factors could promote the regenerative reponse of chronically injured neurons, we exposed the injured adult rat spinal cord to insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF) or transforming growth factor beta 1 + 2 (TGFβs) 1 month after creation of a hemisection lesion. At 1 week later an autologous peripheral nerve graft was apposed to the rostral cavity wall and 1 month later Nuclear Yellow (NY) was used to retrogradely label neurons that had grown an axon into the graft. Neurons capable of axonal regeneration after a long term (5 weeks) injury were double labeled with True Blue (TB, provided at the time of hemisection lesion) and NY. Exposure to any of the three growth factors, compared to a PBS-treated control, resulted in a significant increase in the total number of regenerating supraspinal neurons, with the greatest increase after treatment with TGFβs. Treatment with TGFβs or bFGF led to a significant increase in the number of regenerating neurons in 6 out of 7 major regions (excluding the motor cortex) contributing to descending spinal pathways. Treatment with IGF-1 promoted significant regeneration only by reticular formation neurons. These results indicate that exposure to specific growth factors can enhance axonal regeneration by chronically injured neurons, thus overcoming one significant challenge to the repair of long standing structural damage to the spinal cord. © 1996 Elsevier Science Ireland Ltd. All rights reserved
Memory rehabilitation — recent developments and future directions
Authors: Thöne Angelika I.T.
Published: December 2019

Memory impairment is a frequent effect of different forms of brain injuries and may be even more handicapping than severe physical problems. The purpose of this article is to critically review empirical studies on the effectiveness of different procedures of memory rehabilitation. Traditionally memory rehabilitation has focused on direct training of memory functioning. The problem of these programs is that training effects hardly generalize to patients' everyday life memory problems. As a consequence of this transfer problem, strategies have been developed (method of vanishing cues, errorless learning) which are restricted to the aim of teaching patients domain specific knowledge. Another aspect of memory rehabilitation concentrates on coping with memory impairment. This may be done by alleviating demands on the patient and by including external resources into the process of recovery. On the other hand, teaching the patient to actively cope with memory related difficulties, has recently become an essential objective of memory rehabilitation. In order to pursue this aim, traditional mnemonic techniques are embedded into training of problem solving abilities and metamemory knowledge. Future perspectives and questions open to research are outlined for each of the different procedures.
Peripheral nerve regeneration through microelectrode arrays based on silicon technology
Authors: Navarro Xavier , Calvet Santiago , Butí Miquel , Gómez Nuria , Cabruja Enric , Garrido Paco , Villa Rosa , Valderrama Elena
Published: December 2019

This paper describes some developments, made to obtain a chronic neural interface to record signals from regenerated peripheral nerves. Microperforated silicon dices, fabricated by techniques compatible with CMOS processes, were coupled in silicone nerve chambers and implanted between the severed ends of peripheral nerves in rats. Three configurations of perforated dices with 25 via-holes of 100 μm diameter, 121 via-holes of 40 μm and 400 via-holes of 10 μm were assessed. The feasibility of axonal regeneration through the dices via-holes was proved by histological and physiological methods over 3 months post-implantation. The regenerated nerves were organized in fascicles corresponding to the grid pattern of the via-holes. However, nerve regeneration was difficult and distal re-innervation delayed with respect to simple tubulization repair. The size of the via-holes and the total open area are determinants of the degree and quality of regeneration. Further improvements are needed in both the microelectrode dice design and in neurobiological stimulation of regeneration.
Temporal relationship between the recovery of longitudinal reflex systems and motor recovery in chronic spinally-lesioned rats
Authors: Imai Tomihiro , Aoki Mamoru
Published: December 2019

This study was performed to determine whether a correlation exists in the functional recovery of the longitudinal reflex systems and recovery of quadrupedal locomotion in chronic spinally-lesioned rats. Partial spinal lesions sparing only the right ventral quadrant (VQ) or dorsal quadrant (DQ) of the spinal cord at the lower thoracic (T9–10) levels were performed aseptically under Nembutal anesthesia. Quadrupedal locomotion reappeared within 2–3 weeks after the initial operations in VQ rats. However, no recovery of hindlimb movement was observed in DQ rats. In terminal experiments with VQ and DQ rats, the right brachial plexus (C6–T1) was dissected and mounted on a bipolar stimulating electrode. Spino-bulbo-spinal and interlimb reflex potentials were recorded from bilateral hindlimb muscles under urethane-chloralose anesthesia and Nembutal anesthesia, respectively. In VQ rats, these longitudinal reflex potentials could not be evoked for several days post-operatively. However, the early threshold elevation for evoking the reflex potentials returned gradually to the normal range in accordance with locomotor recovery. In DQ rats, on the other hand, disappearance of the reflex potentials persisted over 1 month observation period. These results suggest that the functional recovery of these longitudinal reflex systems in the ventral quadrant parallels the quadrupedal locomotor recovery after partial spinal cord lesions in rats.
Extract of Ginkgo biloba (EGb 761) improves behavioral performance and reduces histopathology after cortical contusion in the rat
Authors: Hoffman Stuart W. , Stein Donald G.
Published: December 2019

Male rats received bilateral frontal cortex contusions and were injected with 100 mg/kg of EGb 761 or an equal volume of vehicle beginning 5 min after injury and then with 1 injection/day for 7 days. The rats were tested for spontaneous motor behavior on days 1, 5, 10, and 15 postinjury and then for 10 days of spatial navigation performance in the Morris Water Maze (MWM), beginning on the day 8 after the contusion. Brain tissue was removed for examination on the 18th day after injury. Contused rats given EGb 761 performed more like intact rats on measures of spontaneous motor activity while vehicle-treated counterparts remained more active than either shams or EGb 761-treated animals by the conclusion of testing. Contusion-only rats were worse than shams on spatial performance, while those given EGb 761 were less impaired. Histological analyses indicated that EGb 761 failed to prevent loss of tissue at the primary site of impact. However, the extract reduced retrograde degeneration of neurons, gliosis in the thalamus, and ex vacuo hydrocephalus. EGb 761 treatment also decreased the loss of ChAT-positive neurons in the dorsomedial caudate-putamen and in the nucleus basalis magnocellularis (NBM). The results of this study indicate that EGb 761 could be a possible treatment for traumatic brain injury.
Intraventricular encapsulated calf adrenal chromaffin cells: viable for at least 500 days in vivo without detectable adverse effects on behavioral/cognitive function or host immune sensitization in rats
Authors: Lindner Mark D. , Plone Melissa A. , Frydel Beata , Kaplan Faith A. , Krueger Paula M. , Bell William J. , Blaney Thomas J. , Winn Shelley R. , Sherman Sandy S. , Doherty Edward J. , Emerich Dwaine F.
Published: December 2019

Numerous studies have reported that adrenal chromaffin cell transplants, including encapsulated xenogeneic adrenal chromaffin cells, have analgesic effects. However, in addition to efficacy, the clinical utility of encapsulated xenogeneic adrenal chromaffin cells for treatment of chronic pain is dependent on the duration of cell viability in vivo, and their relative safety. The objectives of the present study in rats were to: (1) examine encapsulated calf adrenal chromaffin (CAC) cells for evidence of viable cells and continued release of analgesic agents after an extended period in vivo; (2) determine if intraventricular encapsulated CAC cells produce detectable adverse effects on behavioral/cognitive function; and (3) test for evidence of host immune sensitization after an extended period of exposure to encapsulated xenogeneic adrenal chromaffin cells. Results of the present study suggest that some encapsulated CAC cells remain viable for nearly 1.5 years in vivo and continue to produce catecholamines and met-enkephalin. Post-explant device norepinephrine output was equivalent to amounts previously shown to produce analgesic effects with intrathecal implants. Encapsulated adrenal chromaffin cells also appeared relatively safe, even when implanted in the cerebral ventricals, with a lower side-effect profile than systemic morphine (4 mg/kg). There was no evidence that encapsulated CAC-cells implanted in the ventricles affected body weight, spontaneous activity levels, or performance in the delayed matching to position operant task which is sensitive to deficits in learning, memory, attention, motivation, and motor function. Finally, encapsulated CAC cells produced no detectable evidence of host immune sensitization after 16.7 months in vivo, although unencapsulated CAC cells produced a robust immune response even in aged rats. The results of the present study suggest that adrenal chromaffin cells remain viable in vivo for long periods of time, and that long-term exposure to encapsulated xenogeneic adrenal chromaffin cell implants appears relatively safe.
Reinnervation of rat muscles via volkensin-affected and normal peripheral nerve conduits
Authors: Nógrádi Antal , Vrbová Gerta
Published: December 2019

Volkensin is a neurotoxic lectin which, when injected into a peripheral nerve is retrogradely transported to the cell body and causes it to die. Accordingly, volkensin-affected peripheral nerves rapidly degenerate. It is, however, not clear whether axonal growth can take place within these degenerated nerves. In this study the ability of volkensin-treated and untreated degenerated peripheral nerves to support regeneration of healthy axons was compared. Four groups of animals were used, in Group 1 the peroneal nerve was cut and 10 days later the proximal stump of the deep tibial nerve was sutured to the distal stump of the peroneal nerve (10 days after axotomy). In the second group of animals the peroneal nerve was treated with volkensin, 10 days later the proximal stump of the deep tibial nerve was connected to the distal section of the cut, thus giving a volkensin-treated peroneal nerve. In the third group, 10 days after the peroneal nerve was treated with volkensin, the proximal stump of the deep tibial nerve was connected directly to the extensor digitorum longus (EDL) muscle. In Group 4 the volkensin-treated peroneal nerve was left intact. Six weeks after surgical intervention the tension of both EDL muscles was recorded and the muscles were processed for histological visualisation of endplates and axons. EDL muscles from Group 1 animals produced 36.5 ± 11.3% S.E.M of maximal tetanic tension produced by the contralateral EDL muscle. Significantly less recovery of function was achieved by EDL muscles in Group 2 animals (9.3 ± 2.5%). Muscles from Group 3, where the healthy nerve was sutured directly into the EDL muscle that had been denervated by volkensin treatment had a significantly better recovery than Group 2 muscles (23 ± 3%). Sprouting of nerve fibres and proliferation of Schwann cells was observed in the muscles from Groups 1 and 3, but not in Group 2. Thus, volkensin-treated peripheral nerves provide a poor conduit for regenerating nerve fibres though muscles denervated, by treatment with volkensin, and can accept reinnervation by healthy nerves. The possible mechanisms that render the volkensin treated peripheral stump a poor conduit for healthy axons is discussed.
Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat
Authors: Goldstein Larry B.
Published: December 2019

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.
Resorbable filament structures as a scaffold for matrix formation and axonal growth in bioartificial nerve grafts: long term observations
Authors: Terada Nobuki , Bjursten Lars M. , Papaloïzos Michaël , Lundborg Göran
Published: December 2019

Gaps, 10 mm wide, in rat sciatic nerves were bridged by bioartificial nerve grafts consisting of a silicone tube containing seven longitudinally placed synthetic filaments, which were expected to serve as a scaffold for axonal growth. The filaments were made of non-resorbable material (polyamide [Ethilon®]) or resorbable material (polydioxanon [PDS®], polyglactin [Vicryl®] or catgut). The purpose was to study the influence of resorbable materials on axonal regeneration and to choose, in the long term, the best filament material among the four. After 3 and 6 months, histological techniques were used to study the regenerated nerve structure. The total axon number in the nerve segment distal to the silicone chamber was counted in all specimens at 6 months. The histological findings were different depending on the filament materials; all the three resorbable materials showing significantly larger numbers of axons than polyamide (non-resorbable). All materials were covered with several layers of more or less flattened cells. These results indicate that resorbable filaments are superior to non-resorbable filaments when used as a scaffold inside a silicone tube, and polyglactin seems ideal for this purpose.
Vitamin E attenuates the effects of both reversible and irreversible inhibitors of high-affinity choline transport in vivo
Authors: Stackman Robert W. , Bartolomeo Adam C. , Walsh Thomas J.
Published: December 2019

High-affinity choline transport (HAChT) is the rate limiting step in the synthesis of acetylcholine (ACh). The activity of HAChT and the binding of its selective inhibitor, [3H]hemicholinium-3 (HC-3) are affected by a number of exogenous and endogenous factors. Previous experiments demonstrated that Vitamin E pretreatment could prevent the decrease in HAChT and the cognitive deficits induced by the cholinotoxin AF64A [38]. To further examine this effect these experiments determined whether Vitamin E would alter the efficacy of both irreversible (AF64A) and reversible (HC-3) inhibitors of HAChT. In Experiment 1, rats were pretreated with Vitamin E (50 mg/kg), 24 h and 15 min, prior to bilateral icv injection of AF64A (0, 0.75, 1.5, or 3.0 nmol). HAChT was assessed in hippocampal synaptosomes, 14 days following surgery. Vitamin E prevented the dose-dependent AF64A-induced inhibition of HAChT in the hippocampus (HPC). In a second experiment, rats were pretreated with Vitamin E as above, and infused (icv) with the reversible inhibitor of HAChT, HC-3 (20 μg), or CSF. HAChT in the HPC was assessed 30 min, 4, 12, or 24 h after injection. HC-3 produced a significant decrease of HAChT (58%) that was maximal at 4 h and recovered by 24 h. Vitamin E significantly attenuated, but did not prevent, the inhibition of HAChT produced by HC-3. These experiments demonstrate that Vitamin E pretreatment can attenuate the effects of both reversible and irreversible inhibitors of HAChT. These data are discussed in terms of potential underlying mechanisms. It is possible that the neuroprotectant effects of Vitamin E on both reversible and irreversible inhibitors of HAChT reflect an action at the choline carrier and not an antioxidant effect.
Development of pyramidal cells in medial frontal cortex following neonatal lesions of anterior midline cortex
Authors: De Brabander J.M. , Kolb B.
Published: December 2019

The anterior midline cortex of rats was removed on postnatal day 10. The development of layer II, III and V pyramidal cells in the tissue that subsequently formed the presumptive medial frontal cortex in these animals was studied in Golgi-Cox stained material on postnatal days 15, 25, 35, and 120. The results showed that the number of branch segments of both basilar and apical dendrites were significantly reduced relative to controls at the early developmental stages but by adulthood all regions analyzed were similar in operates and controls. Thus, the cells migrating into the lesion area were delayed in development but did eventually grow to resemble cells that were in the same region in normal controls. This anatomical development correlates with the functional recovery of animals with day 10 frontal lesions in other studies, and suggests that the growth of this tissue may play a role in functional recovery.
Glial cell line-derived neurotrophic factor added to a sciatic	nerve fragment grafted in a spinal cord gap ameliorates motor impairments in	rats and increases local axonal growth
Authors: Guzen Fausto Pierdoná , de Almeida Leme Ricardo José , de Andrade Michele Schultz Ramos , de Luca and Bianca Aparecida , Chadi Gerson
Published: December 2019

Purpose: The aversive nature of regenerative milieu is the main problem related to the failure of neuronal restoration in the injured spinal cord which however might be addressed with an adequate repair intervention. We evaluated whether glial cell line-derived neurotrophic factor (GDNF) may increase the ability of sciatic nerve graft, placed in a gap promoted by complete transections of the spinal cord, to enhance motor recovery and local fiber growth.

Methods: Rats received a 4 mm-long gap at low thoracic level and were repaired with a fragment of the sciatic nerve. GDNF was added (NERVE±GDNF) or not to the grafts (NERVE--GDNF). Motor behavior score (BBB) and sensorimotor tests-linked to the combined behavior score (CBS), which indicate the degree of the motor improvement and the percentage of functional deficit, respectively, and also the spontaneous motor behavior in an open field by means of an infrared motion sensor activity monitor were analyzed. At the end of the third month post surgery, the tissue composed by the graft and the adjacent regions of the spinal cord was removed and submitted to the immunohistochemistry of the neurofilament-200 (NF-200), growth associated protein-43 (GAP-43), microtubule associated protein-2 (MAP-2), 5-hidroxytryptamine (serotonin, 5-HT) and calcitonin gene related peptide (CGRP). The immunoreactive fibers were quantified at the epicenter of the graft by means of stereological procedures.

Results: Higher BBB and lower CBS levels (p < 0.001) were found in NERVE±GDNF rats. GDNF added to the graft increased the levels of individual sensorimotor tests mainly at the third month. Analysis of the spontaneous motor behavior showed decreases in the time and number of small movement events by the third month without changes in time and number of large movement events in the NERVE$+$GDNF rats. Immunoreactive fibers were encountered inside the grafts and higher amounts of NF-200, GAP-43 and MAP-2 fibers were found in the epicenter of the graft when GDNF was added. A small amount of descending 5-HT fibers was seen reentering in the adjacent caudal levels of the spinal cords which were grafted in the presence of GDNF, event that has not occurred without the neurotrophic factor. GDNF in the graft also led to a large amount of MAP-2 perikarya and fibers in the caudal levels of the cord gray matter, as determined by the microdensitometric image analysis.

Conclusions: GDNF added to the nerve graft favored the motor recovery, local neuronal fiber growth and neuroplasticity in the adjacent spinal cord.
Effects of Schwann cell transplants in an experimental nerve	amputee model
Authors: Lago Natalia , Casas Caty , Muir Elizabeth M. , Rogers John , Navarro Xavier
Published: December 2019

Purpose: By using a nerve amputee model of the rat sciatic nerve (Lago and Navarro, 2007), we have tested a strategy for the long-term maintenance of regenerated axons without distal target reinnervation, by grafting Schwann cells (SCs) into a capped silicone chamber containing the ending nerve stump.

Methods: The sciatic nerve of rats was transected and repaired with a silicone tube, the distal nerve was again cut at 10 mm and inserted in a capped tube that was filled with saline or with a suspension of cultured SCs. Transplants of SCs obtained from primary cultures have been compared with those of an immortalized SC line (SCTM41) or the same line overexpressing GDNF.

Results: The histological results show that nerve fibers were able to regenerate through a short distal nerve segment ending into the capped chamber, and sustain distal branches without degenerating for several months. There was abundant axonal sprouting forming an ending neuroma, and the caliber of myelinated fibers remained far thinner than normal during the 9 months investigated. With a distal transplant of primary SCs there were significantly more regenerated myelinated fibers than in the control group at 9 months, indicating that the grafted cells stimulated the axonal growth response and helped to maintain survival of axon branches. In contrast, axonal regeneration was significantly reduced with grafts of SCTM41 cells, probably due to physical competition between cell proliferation and axonal growth. SCTM41 cells overexpressing GDNF improved the regenerative response with respect to the parent SCTM41 cells, although not to the same extent as the primary SCs.

Conclusion: A graft of primary SCs in the capped chamber stimulated axonal growth response and/or maintained survival of axonal branches on the long term in the nerve amputee model.
Manual stimulation, but not acute electrical stimulation prior to	reconstructive surgery, improves functional recovery after facial nerve injury	in rats
Authors: Skouras Emmanouil , Merkel Daniel , Grosheva Maria , Angelova Srebrina K. , Schiffer Gereon , Thelen Ulrich , Kaidoglou Katerina , Sinis Nektarios , Igelmund Peter , Dunlop Sarah A. , Pavlov Stoyan , Irintchev Andrey , Angelov Doychin N.
Published: December 2019

The outcome of peripheral nerve injuries requiring surgical repair is poor. Recent work suggested that electrical stimulation (ES) of the proximal nerve stump to produce repeated discharges of the parent motoneurons for one hour could be a beneficial therapy if delivered immediately prior to reconstructive surgery of mixed peripheral nerves.

Purpose: We tested whether ES has a positive influence on functional recovery after repair of a purely motor nerve, the facial nerve.

Methods: Electrical stimulation (20 Hz) was delivered to the proximal nerve stump of the transected facial nerve for 1 hour prior to nerve reconstruction by end-to-end suture (facial-facial anastomosis, FFA). For manual stimulation (MS), animals received daily rhythmic stroking of the whisker pads. Restoration of vibrissal motor performance following ES or MS was evaluated using video-based motion analysis. We also assessed the degree of collateral axonal branching at the lesion site, by counting motoneuronal perikarya after triple retrograde labeling, and estimated the quality of motor end-plate reinnervation in the target musculature. Outcomes at 4 months were compared to animals receiving sham stimulation (SS) or MS.

Results: Neither protocol reduced the degree of collateral sprouting. ES did not improve functional outcome and failed to reduce the proportion of polyinnervated motor end-plates. By contrast, MS restored normal whisking function and reduced polyinnervation.

Conclusion: Whereas acute ES is not beneficial for facial nerve repair, MS provides long-term benefits.
Cortical activation during finger tracking vs. ankle tracking in	healthy subjects
Authors: LaPointe Kyle E. , Klein Jacob A. , Konkol Meagan L. , Kveno Sara M. , Bhatt Ela , DiFabio Richard P. , Carey James R.
Published: December 2019

Purpose: Explore in healthy subjects whether the differences in cortical activation between ankle and finger movements observed in earlier studies with no attention to accuracy also apply to accuracy-demanding tasks.

Methods: Twenty healthy subjects performed right-finger and right-ankle tracking tasks during functional magnetic resonance imaging. Cortical activation was analyzed in the primary motor area (M1), primary somatosensory area (S1), supplementary motor area (SMA), and premotor cortex (PMC). The blood-oxygen-level-dependent signal intensity of active voxels was compared between the finger and ankle conditions.

Results: The results indicated that finger tracking exhibited greater intensity in contralateral (left) M1 and S1 compared to ankle tracking, and ankle tracking exhibited greater intensity in both contralateral and ipsilateral SMA compared to finger tracking. Both M1 and S1 showed more lateralized (contralaterally) organization during finger tracking compared to ankle tracking. Activation maps derived from contrasting the two tracking conditions to each other suggested that ipsilateral areas serve an important role in accuracy-demanding tasks. Regression analysis revealed signal intensity in contralateral M1 and ipsilateral S1 as significant variables in predicting tracking accuracy, but only for finger tracking.

Conclusions: Differences in lateralization between finger and ankle performance found earlier (Kapreli et al., 2006) during simple movement tasks also hold for accuracy-demanding tasks, but dissimilarity in brain organization exists in that the latter show greater ipsilateral activity for both joints. These results invite further research on controlled movements in the lower limb to promote favorable brain reorganization and recovery in people with brain injury.
Progesterone decreases cortical and sub-cortical edema in young	and aged ovariectomized rats with brain injury
Authors: Kasturi Badrinarayanan S. , Stein Donald G.
Published: December 2019

Purpose: Traumatic brain injury (TBI) -induced brain edema can be reduced by acute progesterone (PROG) treatment in young adult males and females, and in aged males. To extend these findings we tested these hypotheses: 1. Acute PROG treatment post-TBI will reduce cortical edema in aged females as much as in young adults. 2. TBI will induce edema in sub-cortical structures (SCS): the thalamus (TH), hypothalamus (HT), brain stem (BS) and anterior pituitary (AP). 3. Acute, systemic PROG treatment post-TBI will reduce edema in SCS.

Methods: Young adult (n=42) and aged (n=40), bilaterally ovariectomized rats were given medial frontal cortical (MFC) contusion injury, treated with PROG (16 mg/kg body weight) or vehicle at 1, 6 and 24 hours post-injury and killed at 6, 24 and 48 hours post-injury. Their brains were removed and the target areas isolated and measured for water content.

Results: TBI induced cortical and delayed sub-cortical edema. Acute PROG treatment decreased this edema. At 6 hours post-TBI serum PROG levels were substantially elevated in both young and aged, PROG-treated, groups, but were higher in the latter.

Conclusion: Acute PROG treatment post-TBI could prove an effective intervention to prevent or attenuate systemic, post-injury cortical and sub-cortical edema in young and aged females.
Peripheral nerve grafts in a spinal cord prosthesis result in	regeneration and motor evoked potentials following spinal cord resection
Authors: Nordblom Jonathan , Persson Jonas K.E. , Svensson Mikael , Mattsson Per
Published: December 2019

Purpose: To evaluate whether a standardized nerve graft bridging of a spinal cord injury gap in a device with white to grey matter projections allows regeneration and electrophysiological contact from supraspinal centers to the leg, since previous studies using nerve grafts in combination with acidic fibroblast growth factor have been difficult to microsurgically reproduce.

Methods: A moulded prosthesis containing twelve peripheral nerve grafts with estimated pre-set projections guiding white tracts to grey matter replaced a spinal cord resection gap at level T11 in adult rats. The animals were evaluated with electrophysiology, morphology, immunohistochemistry and functional scoring.

Results: At six months postoperatively the grafts were found to be positioned at the desired locations, motor evoked potentials were detected in 80% of the animals subjected to nerve graft bridging. Morphology and immunohistochemical analysis revealed numerous de novo axons in the grafts, which possibly reached into the spinal cord on the other side.

Conclusion: Replacing the resected spinal cord with oblique peripheral nerve grafts results in spinal cord regeneration and positive motor evoked potential. Transplantation of nerve grafts organized in a prosthesis is re-producible, sustains desired projections and ensures transverse ends towards the spinal cord surface and may be useful in the future.
Autologous bone marrow stem cell neurotransplantation in stroke	patients. An open study
Authors: Suárez-Monteagudo Carlos , Hernández-Ramírez Porfirio , Álvarez-González Lázaro , García-Maeso Iván , de la Cuétara-Bernal Karelys , Castillo-Díaz Lázara , Bringas-Vega María L. , Martínez-Aching Gilda , Morales-Chacón Lilia M. , Báez-Martín Margarita M. , Sánchez-Catasús Carlos , Carballo-Barreda Maylen , Rodríguez-Rojas Rafael , Gómez-Fernández Lázaro , Alberti-Amador Esteban , Macías-Abraham Consuelo , Balea Elvira Dorticós , Rosales Lázaro Cortina , del Valle Pérez Lázaro , Ferrer Berta B. Socarrás , González Raúl Macías , Bergado Jorge A.
Published: December 2019

Purpose: Bone marrow stem cells (BMSC) were transplanted into the perilesional area in five patients bearing sequels of stroke, to evaluate the safety of the procedure and tolerance to the transplanted cells.

Methods: Cells were obtained from bone marrow samples taken from the same patient and stereotactically implanted into the targets, determined using a combination of images, and trans-operative recording of multiunit activity. The cells were implanted in several points along tracts in the perilesional region.

Results: No important adverse events derived from surgery or transplant were observed during the one year follow-up period, or detected using a combination of tests and functional measurements applied pre- and post-surgically. In contrast, some improvements were observed regarding the neurological condition of the patients, but the small number of patients in the study does not allow any conclusive statement.

Conclusions: Our results demonstrate that BMSC can be safely transplanted into the brain of patients, with excellent tolerance and without complications, using the methods described here.
Memory training effects in old age as markers of plasticity: A	meta-analysis
Authors: Zehnder Franzisca , Martin Mike , Altgassen Mareike , Clare Linda
Published: December 2019

In most studies on plasticity using behavioural data, cognitive plasticity has been studied in the context of short-term interventions such as memory training. In order to systematically review the literature on memory training and summarize its effects for old healthy people and people with mild cognitive impairment on multiple functional domains, we conducted a meta-analysis of all published randomized controlled trials (RCT) between 1970 and 2007. Overall, 24 studies examining memory training effects in healthy and in mildly cognitively impaired old adults were identified and included in the analysis. Only memory trainings (e.g. memory skills training, imagery, method of loci) with cognitive outcome measures, duration of intervention with up to one year with at least a baseline and a post-intervention assessment reported, were included.

Results demonstrate significant training effects for paired associate learning and immediate and delayed recall in healthy old adults and for immediate recall in mildly cognitively impaired old adults. However, training effects were no larger than those found for active control conditions. Our results suggest that evidence on the effectiveness and specificity of training interventions is scarce. We discuss limitations of existing knowledge about the efficacy of memory training interventions and implications for future research to improve knowledge regarding effective cognitive interventions.
Training of the executive component of working memory: Subcortical	areas mediate transfer effects
Authors: Dahlin Erika , Bäckman Lars , Neely Anna Stigsdotter , Nyberg Lars
Published: December 2019

Purpose: Several recent studies show that training can improve working memory (WM) performance. In this review, many issues related to WM training, such as neural basis, transfer effects, and age-related changes are addressed.

Method: We focus on our own studies investigating training on tasks taxing the executive updating function and discuss our findings in relation to results from other studies investigating training of the executive component of WM.

Results: The review confirms positive behavioral effects of training on working memory. The most common neural pattern following training is fronto-parietal activity decreases. Increases in sub-cortical areas are also frequently reported after training, and we suggest that such increases indicate changes in the underlying skill following training. Transfer effects are in general difficult to demonstrate. Some studies show that older adults increase their performance after WM training. However, transfer effects are small or nonexistent in old age.

Conclusions: The main finding in this review is that sub-cortical areas seem to have a critical role in mediating transfer effects to untrained tasks after at least some forms of working memory training (such as updating).
Cognitive plasticity in adulthood and old age: Gauging the	generality of cognitive intervention effects
Authors: Noack Hannes , Lövdén Martin , Schmiedek Florian , Lindenberger Ulman
Published: December 2019

Interventions enabling aging individuals to fulfill their plastic potential promise to postpone, attenuate, or even reverse the adverse effects of senescent brain changes on cognitive abilities and everyday competence in old age. Based on an overview of the concept of plasticity in lifespan development, we selectively review evidence from cognitive intervention studies and conclude that most of them have failed to observe generalizable performance improvements, as documented by the small size and scope of positive transfer to untrained tasks. We further note that generally accepted criteria for defining transfer distance are lacking, rendering the relevant evidence difficult to interpret. Hence, we propose a taxonomy of transfer distance based on the structure of human intellectual abilities.
Flexible and adaptive socio-emotional problem solving in adult	development and aging
Authors: Blanchard-Fields Fredda
Published: December 2019

Purpose: Despite decline in basic cognitive mechanisms, aging adults may also possess abilities that allow them to function quite effectively, particularly when cognition is examined in a socio-emotional context. In this article, I highlight the importance of the functional dynamics or the ability to effectively adapt to the demands and opportunities that individuals are confronted with on an everyday basis.

Methods: This overview takes into consideration how life experiences, social interactions, beliefs, and emotions influence motivational goals for processing information in daily life. I present an integrative representation of my empirical work and theorizing on the impact of socio-emotional contextual factors in older adulthood by identifying developmental mechanisms and contexts that determine when older adults' everyday problem solving and emotion regulation is optimal or adaptive and when it is not.

Results: Older adults display flexibility in problem solving and emotion regulation strategy use as well as a decrease in the amount of resources necessary to maintain or regain emotional well-being, while performing well at other tasks.

Conclusions: We suggest that growing older has the adaptive potential to effectively solve problems, regulate emotions, and reduce the cognitive costs of emotion regulation, further corroborating findings of a positive and flexible developmental trajectory for emotional control with increasing age.
Human embryonic stem cells which express hrGFP in the	undifferentiated state and during dopaminergic differentiation
Authors: Chen Jia , Tsai Shang-Yi , Vazin Tandis , Coggiano Mark , Freed William J.
Published: December 2019

Purpose: human embryonic stem cells (hESCs) which express a reporter gene consistently during all phases of differentiation would be valuable for basic research on cell transplantation. In this study, we describe karyotypically-abnormal variant hESCs, BGO1V2-EFG, which express hrGFP driven by the EF1 promoter.

Methods: BGO1V2-EFG cells were analyzed by using immunocytochemistry, single cell-based confocal image, and in vitro differentiation, including dopaminergic differentiation.

Results: Undifferentiated BGO1V2-EFG cells expressed pluripotent ESC markers and retained the ability to differentiate into cell types of all three germ layers. BGO1V2-EFG cells maintained stable and robust hrGFP expression in vitro in the undifferentiated state and during differentiation. The EF1 promoter retained activity during dopaminergic differentiation, as 76% of tyrosine hydroxlase (TH)-positive cells co-expressed hrGFP by confocal analysis. Treated with sodium butyrate (0.02 mM to 2.0 mM), an inhibitor of histone deacetylase (HDAC), during differentiation did not affect hrGFP expression, although TH expression was reduced by higher concentrations of sodium butyrate.

Conclusion: BGO1V2-EFG cells maintain stable and robust hrGFP expression in the undifferentiated state and during neural differentiation. Especially, the EF1 promoter was effective in driving hrGFP expression during dopaminergic differentiation. BGO1V2-EFG cells may be useful for transplantation studies in Parkinson disease animal models.
Cognitive training and plasticity: Theoretical perspective and	methodological consequences
Authors: Willis Sherry L. , Schaie K. Warner
Published: December 2019

Purpose. To provide an overview of cognitive plasticity concepts and findings from a lifespan developmental perspective. Methods. After an evaluation of the general concept of cognitive plasticity, the most important approaches to study behavioral and brain plasticity are reviewed. This includes intervention studies, experimental approaches, cognitive trainings, the study of facilitating factors for strategy learning and strategy use, practice, and person-environment interactions. Transfer and durability of training-induced plasticity is discussed. Results. The review indicates that methodological and conceptual advances are needed to improve the match between levels of behavioral and brain plasticity targeted in current developmental research and study designs. Conclusions. The results suggest that the emphasis of plasticity studies on treatment effectiveness needs to be complemented by a strong commitment to the grounding of the intervention in a conceptual framework.
Imaging cortical activity after vestibular lesions
Authors: Dieterich Marianne , Brandt Thomas
Published: December 2019

In this article we will discuss our current knowledge of multisensory vestibular structures and their functions in the human cortex. Most of it derives from brain activation studies with PET and fMRI in humans conducted over the last decade. They have confirmed the existence of several separate and distinct cortical areas that were identified earlier by tracer and electrophysiological studies in animals, especially in monkeys. The patterns of activations and deactivations during vestibular stimulations in healthy subjects have been compared with those in patients with acute and chronic peripheral and central vestibular disorders. The following reviews what is presently known about the interconnections of vestibular structures, their activations and interactions with other sensory modalities, the correlations of perceptual and motor functions in normal humans, and the changes that result from strategic unilateral peripheral and central vestibular lesions such as vestibular neuritis and bilateral vestibular failure, on the one hand, and central vestibular nucleus lesions due to ischemic infarctions of the lateral medulla (Wallenberg's syndrome), on the other.
In vitro differentiation of GABAergic cells from bone marrow	stromal cells using Potassium Chloride as inducer
Authors: Gharibani Payam Mohammad , Tiraihi Taki , Arabkheradmand Jalil
Published: December 2019

Bone marrow stromal cells (BMSCs) are multipotent and can be induced to differentiate into different lineages including osteogenic, chondrogenic, myogenic and neuronal phenotypes. BMSCs were reported to be a suitable option for regenerative medical research. In this study, BMSCs were induced into GABAergic phenotypes using β-mercaptoethanol (βME) and retinoic acid (RA) as preinducers followed by potassium chloride as inducer, and were evaluated by fibronectin and Oct-4. The percentages of cells immunoreactive for nestin, neurofilaments (NF 68, NF 160, and NF 200), GABA and GABA synthesizing and packaging enzymes (GAD1, GAD2, VGAT) were used for evaluating GABAergic differentiation. RT-PCR was used for confirming the expression of these enzymes. The differentiated cells were loaded and unloaded with FM1-43 in order to assess the functionality of the cells. At the preinduction stage, the cells downregulated fibronectin and Oct-4, and expressed neuronal markers. At the induction stage, the preinduced cells transdifferentiated into GABAergic cells, as confirmed by immunohistochemistry and RT-PCR. The GABAergic cells were stained and destained with FM1-43. Therefore, the two-stage induction protocol resulted in transdifferentiation of BMSCs into GABAergic cells with synaptic release upon stimulation.
A case of pathological excitability located with navigated-TMS:	Presurgical evaluation of focal neocortical epilepsy
Authors: Schmidt Sein , Holst Eric , Irlbacher Kerstin , Oltmanns Frank , Merschhemke Martin , Brandt Stephan A.
Published: December 2019

Purpose: The quality of presurgical evaluation in focal extratemporal epilepsy surgery is highly dependent on precise structural and functional identification of the epileptic focus. Navigated transcranial magnetic stimulation (nTMS) is a tool that combines the spatial information of high-resolution magnetic resonance imaging (MRI) with the functionality of non-invasive cortical stimulation. The non-invasive character of nTMS suggests that it could be a promising tool for presurgical evaluation of cortical excitability.

Methods: Presurgical nTMS evaluation was performed on an 8-year-old boy with left-sided intractable focal epilepsy, somatosensory auras and epilepsia partialis continua. In line with standardized procedures, motor evoked potentials were sought in both hemispheres over perirolandic cortex during simultaneous belly-tendon surface recordings of the first dorsal interosseus muscles.

Results: One singular motor-evoked potential (MEP) could be elicited in the unaffected hemisphere. In contrast, in the affected hemisphere MEPs could be elicited over a large area of the cortex even after the stimulation strength was reduced by at least 44%. Latency stratification in the affected hemisphere differentiated a motor from a sensory region of interest. Stimulation over the sensory region induced a sensory aura. The sensory site was concordant with a previous transient diffusion restriction found in an MRI two years prior to nTMS.

Conclusions: NTMS can locate pathological excitability with high spatial precision. Future studies should compare nTMS with direct cortex stimulation, as well as the combination of nTMS with electroencephalography (EEG) in a larger patient-collective.
Noninvasive brain stimulation and motor recovery after	stroke
Authors: Nowak Dennis A. , Bösl Kathrin , Podubeckà Jitka , Carey James R.
Published: December 2019

Purpose: Upper limb function is the best predictor of long-term disability after stroke. Despite extensive rehabilitation, recovery of upper limb motor function is frequently incomplete after stroke.

Methods: We review the pertinent literature on functional reorganization within the cerebral motor network after stroke and noninvasive techniques to modulate brain function towards beneficial plasticity.

Results: Direct current stimulation and repetitive transcranial magnetic stimulation are powerful tools to (i) modulate cortical excitability, (ii) induce remote changes within the cortical motor system and (iii) thereby improve upper limb motor function after stroke. Today no relevant side effects have been reported.

Conclusions: Neuromodulation, by means of noninvasive brain stimulation techniques, has been shown to be a safe, feasible and effective method to promote recovery of motor function after stroke. However, several methodological and theoretical issues remain to be addressed in future work.
Research with rTMS in the treatment of aphasia
Authors: Naeser Margaret A. , Martin Paula I. , Treglia Ethan , Ho Michael , Kaplan Elina , Bashir Shahid , Hamilton Roy , Coslett H. Branch , Pascual-Leone Alvaro
Published: December 2019

This review of our research with rTMS to treat aphasia contains four parts: Part 1 reviews functional brain imaging studies related to recovery of language in aphasia with emphasis on nonfluent aphasia. Part 2 presents the rationale for using rTMS to treat nonfluent aphasia patients (based on results from functional imaging studies). Part 2 also reviews our current rTMS treatment protocol used with nonfluent aphasia patients, and our functional imaging results from overt naming fMRI scans, obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy (CILT). Part 4 reviews our diffusion tensor imaging (DTI) study that examined white matter connections between the horizontal, midportion of the arcuate fasciculus (hAF) to different parts within Broca's area (pars triangularis, PTr; pars opercularis, POp), and the ventral premotor cortex (vPMC) in the RH and in the LH. Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients.