Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nestin is a neurofilament protein expressed by the immediate precursors to neurons and glia in rats and humans. Nestin immunoreactivity in the rat CNS was studied following kainic acid (KA) hippocampal lesions. Numerous nestin positive cells within the KA lesion were confirmed to be reactive astrocytes by their immunoreactivity for glial fibrillary acidic protein (GFAP). The number of these cells decreased with time after the KA lesion and no astrocyte immunostaining for nestin was observed in control animals. A subset of nestin-positive cells in the ventricular subependymal region appeared to be radial glial cells, extending to cell body layers. Nestin is one of several embryonic markers expressed by reactive astrocytes, suggesting an embryonic reversion induced by the KA lesion, possibly to enhance functional recovery.
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PMID:Reactive astrocytes express the embryonic intermediate neurofilament nestin. 784 69

We have shown previously that epidermal growth factor (EGF) plus fibroblast growth factor (FGF2) expands the neural precursor cells in the ependyma of the normal adult rat spinal cord in vivo. To investigate the therapeutic effect of these factors on spinal cord injury (SCI), we administered EGF, FGF2, EGF plus FGF2, or artificial cerebrospinal fluid (aCSF) intrathecally (15 ng/h of EGF or FGF2) for 3 or 14 days after mild (2.4-g) or moderate (20-g) clip compression injury at T1 in adult rats. Histological and functional assessments were used to evaluate the therapeutic effects. The EGF plus FGF2 group, which received these agents for 14 days, showed better functional recovery than the aCSF group 42 days after moderate SCI (p < 0.05). At 14 days, the EGF plus FGF2 group showed a much greater expansion of ependymal cells and astrocytes compared to the other groups, and there was evidence for extensive migration of ependymal cells into the surrounding injured cord. These mitogens did not significantly enhance nestin expression in the ependymal layer or alter the expansion of oligodendrocyte precursor cells or microglia/macrophages, and dividing cells did not show the neuron-specific marker NeuN except immediately adjacent to the ependyma. The exact mechanism for improved functional recovery after EGF plus FGF2 is not known.
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PMID:Intrathecal administration of epidermal growth factor and fibroblast growth factor 2 promotes ependymal proliferation and functional recovery after spinal cord injury in adult rats. 1189 24

Although the juvenile human brain is relatively radioresistant, irradiation can result in brain growth retardation, progressive mental disturbance, and neurologic abnormalities. As neural stem cells or progenitor cells may be a target of radiation injury and may play an important role in the brain's functional recovery, we examined the effects of whole brain irradiation on these cells in juvenile rat. Six-week-old Wistar rats, where the brain is still growing, were irradiated with single doses of 1, 2, or 3 Gy X-ray. We measured their body and brain weights at 30 or 60 days after irradiation. The chronological changes of the subventricular zone (SVZ) were examined at 6 h, 2, 7, 14, 30, or 60 days after irradiation by immunohistochemistry, specifically looking at the neural stem cells or progenitor cells using anti-nestin antibodies specific for these cells. The rate of brain weight gain of irradiated rats significantly decreased in comparison to controls, although that of body weight gain was similar among them. Multiple apoptotic cells appeared in the SVZ at 6 h after irradiation with simultaneous reduction in nestin-positive cells (69% of the control). The cell levels recovered within a week, with the nestin-positive cells reaching maximal numbers (182%) on Day 14. Nestin-positive cells returned to baseline levels within 30 days (96%) and remained unchanged for the subsequent 60 days. The X-ray dosage did not affect these findings. Our findings revealed that single low dose X-ray administration reversibly affected the levels of neural stem and progenitor cells in the SVZ region. These results suggest that continuous multiple administrations of X-rays in clinical treatment may affect irreversible changes on neural stem or progenitor cells, causing brain growth retardation, or dysfunction.
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PMID:Effects of single low dose irradiation on subventricular zone cells in juvenile rat brain. 1250 Jul 5

The ability of implanted embryonic neural stem cells (NSCs) to improve survival, migration, and functional recovery following a compression spinal cord injury (SCI) was tested in adult rats. NSCs were isolated from E14-16 rat cerebral cortex and SCI was produced by using an aneurysm clip applicator applied to the 8th thoracic spinal cord according to method of Dolan and Tator. Two weeks after the injury, NSCs (4 microl of 1 x 10(4) cells/microl) were injected into the lesion site. The grafted NSCs were noted to survive and integrate with the host spinal cord 1 month after transplantation, which was demonstrated by the presence of Hoechst 33342 (a nuclear dye) pre-labeled NSCs within and surrounding the lesion site. Some of these cells remained undifferentiated and were stained with nestin, a marker for NSCs. Transplanted NSCs migrated for at least 3 mm from the injury epicenter towards both the rostral and caudal directions. Significant reduction in the lesion area (P<0.05) and improvement in inclined plane (P<0.05) and BBB locomotor rating scale (P<0.05) were found in the cases that received implantation of NSCs, as compared with those that received vehicle injection. More importantly, when glial cell line-derived neurotrophic factor (GDNF; 1.5 microg/microl) was added to the transplants, further reduction in lesion area (P<0.01) and improvement in the function were observed in the combined treatment group as compared with the vehicle infused group. Our results suggest that intraspinal treatment with NSCs and GDNF synergistically reduced lesion size and improved functional outcome after a compressive SCI in adult rats.
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PMID:[Effects of embryonic neural stem cells and glial cell line-derived neurotrophic factor in the repair of spinal cord injury]. 1281 5

We have investigated the potential of human pluripotent cells to restore function in rats paralyzed with a virus-induced motor neuronopathy. Cells derived from embryonic germ cells, termed embryoid body-derived (EBD) cells, introduced into the CSF were distributed extensively over the rostrocaudal length of the spinal cord and migrated into the spinal cord parenchyma in paralyzed, but not uninjured, animals. Some of the transplanted human cells expressed the neuroglial progenitor marker nestin, whereas others expressed immunohistochemical markers characteristic of astrocytes or mature neurons. Rare transplanted cells developed immunoreactivity to choline acetyltransferase (ChAT) and sent axons into the sciatic nerve as detected by retrograde labeling. Paralyzed animals transplanted with EBD cells partially recovered motor function 12 and 24 weeks after transplantation, whereas control animals remained paralyzed. Semi-quantitative analysis revealed that the efficiency of neuronal differentiation and extension of neurites could not account for the functional recovery. Rather, transplanted EBD cells protected host neurons from death and facilitated reafferentation of motor neuron cell bodies. In vitro, EBD cells secrete transforming growth factor-alpha (TGF-alpha) and brain-derived neurotrophic factor (BDNF). Neutralizing antibodies to TGF-alpha and to BDNF abrogated the ability of EBD-conditioned media to sustain motor neuron survival in culture, whereas neutralizing antibodies to BDNF eliminated the axonal outgrowth from spinal organotypics observed with direct coculture of EBD cells. We conclude that cells derived from human pluripotent stem cells have the capacity to restore neurologic function in animals with diffuse motor neuron disease via enhancement of host neuron survival and function.
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PMID:Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury. 1283 37

The current study examines nestin expression after intracerebral hemorrhage (ICH), the role of different blood components in nestin upregulation, and the possibility that low doses of thrombin that induce tolerance to brain injury (thrombin preconditioning) might also induce nestin expression. Adult male Sprague-Dawley rats received an intracaudate injection of either whole blood, thrombin (1 or 5 U) or red blood cells (RBCs). Animals were sacrificed for single and double labeling immunohistochemistry to identify which cells express nestin, and for Western blotting to quantify nestin expression. By immunohistochemistry, nestin immunoreactivity was present in large numbers of astrocytes, surrounding the hematoma from day 3 to 1 week after ICH. After 2 weeks, nestin immunoreactivity was co-localized with a neuronal marker (neuronal specific enolase). By Western blot analysis, nestin was strongly expressed at day 3 (P<0.01) and 1 week (P<0.01), and expression persisted for at least 1 month (P<0.05). Intracerebral injection of thrombin or lysed RBCs resulted in a marked increase in nestin expression. Interestingly, injection of a low dose of thrombin that induces brain tolerance also upregulated nestin. The ICH-induced nestin expression in astrocytes may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury perhaps leading to recovery of function. Nestin induction by a low dose of thrombin suggests that specific receptor-mediated pathways are involved in inducing nestin expression and that nestin may play a role in thrombin preconditioning.
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PMID:Nestin expression after experimental intracerebral hemorrhage. 1288 31

Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea, leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in the adult rat. We report that in Sprague-Dawley rats the initial IH-induced impairments in spatial learning are followed by a partial functional recovery over time, despite continuing IH exposure. These functional changes coincide with initial decreases in basal neurogenesis as shown by the number of positively colabelled cells for BrdU and neurofilament in the dentate gyrus of the hippocampus, and are followed by increased expression of neuronal progenitors and mature neurons (nestin and BrdU-neurofilament positively labelled cells, respectively). In contrast, no changes occurred during the course of IH exposures in the expression of the synaptic proteins synaptophysin, SNAP25, and drebrin. Collectively, these findings indicate that the occurrence of IH during the lights on period results in a biphasic pattern of neurogenesis in the hippocampus of adult rats, and may account for the observed partial recovery of spatial function.
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PMID:Temporal aspects of spatial task performance during intermittent hypoxia in the rat: evidence for neurogenesis. 1462 95

Transplantation of stem and neural progenitor cells hold great promise in the repair of neuronal tissue lost due to injury or disease. However, survival following transplantation to the adult CNS has been poor, likely due to a lack of neurotrophic factors, such as basic fibroblast growth factor (FGF-2), that are used to maintain and expand these cells in culture. Chromaffin cells produce several neurotrophic agents, including FGF-2, which may aid in both neuroprotection following injury and progenitor cell proliferation and survival. In addition, increased CNS catecholamines have been shown to improve functional recovery following insult. Thus, cotransplants of neural progenitor cells and chromaffin cells may be a useful clinical strategy. To address this, the survival of rat cortical progenitors transplanted to the adult rat striatum with and without bovine chromaffin cell cografts was assessed. Progenitors obtained from E14 embryos were prelabeled with bromodeoxyuridine (BrdU) before transplantation to enable later identification. Transplants were made both unilaterally and bilaterally, where animals received a monograft (progenitor cells alone) on one side and a cograft (progenitors + chromaffin cells) on the other. Histological results after 7, 17, and 30 days posttransplant revealed greatly improved survival of BrdU-labeled cells in the cografts and also less infiltration of presumptive immune cells. In addition, perivascular cuffing was seen in the monografts. In vitro progenitor cohorts stained positive for nestin, GFAP, and beta-tubulin III, but in vivo very few cells were found that were double labeled with BrdU and one of these markers. Thus, in contrast to in vitro findings, chromaffin cells did not enhance differentiation of progenitors in vivo during the 30 days posttransplantation. The results of these studies suggest that chromaffin cells may provide neurotrophic support to enhance survival, but not differentiation, of cortical progenitor grafts in the adult CNS.
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PMID:Improved neural progenitor cell survival when cografted with chromaffin cells in the rat striatum. 1469 24

Previous reports showed the therapeutic effect of transplants of bone marrow stromal cells (BMSC) after incomplete traumatic spinal cord lesions. We studied the effect of this form of therapy in chronically paraplegic Wistar rats due to severe spinal cord injury (SCI). Rats were subjected to weight-drop impact causing paraplegia, and BMSC or phosphate buffered saline (PBS) was injected into spinal cord 3 months after injury. Functional outcome was measured using the Basso-Beattie-Bresnehan score until sacrifice of the animals, 4 weeks after transplantation. At this time, samples of spinal cord tissue were studied histologically. The results showed a clear and progressive functional recovery of the animals treated with BMSC transplantation, compared to controls. Grafted BMSC survived into spinal cord tissue, forming cell bridges within the traumatic centromedullary cavity. In this tissue, cells expressing neuronal and astroglial markers can be seen, together with a marked ependymal proliferation, showing nestin-positivity. These findings suggest the utility of BMSC transplantation in chronically established paraplegia.
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PMID:Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation. 1512 54

Here, we investigate the effects of endothelial nitric oxide synthase (eNOS) on angiogenesis, neurogenesis, neurotrophic factor expression, and neurological functional outcome after stroke. Wild-type and eNOS knock-out (eNOS-/-) mice were subjected to permanent occlusion of the right middle cerebral artery. eNOS-/- mice exhibited more severe neurological functional deficit after stroke than wild-type mice. Decreased subventricular zone (SVZ) progenitor cell proliferation and migration, measured using bromodeoxyuridine, Ki-67, nestin, and doublecortin immunostaining in the ischemic brain, and decreased angiogenesis, as demonstrated by reduced endothelial cell proliferation, vessel perimeter, and vascular density in the ischemic border, were evident in eNOS-/- mice compared with wild-type mice. eNOS-deficient mice also exhibited a reduced response to vascular endothelial growth factor (VEGF)-induced angiogenesis in a corneal assay. ELISAs showed that eNOS-/- mice have decreased brain-derived neurotrophic factor (BDNF) expression but not VEGF and basic fibroblast growth factor in the ischemic brain compared with wild-type mice. In addition, cultured SVZ neurosphere formation, proliferation, telomerase activity, and neurite outgrowth but not cell viability from eNOS-/- mice were significantly reduced compared with wild-type mice. BDNF treatment of SVZ cells derived from eNOS-/- mice restored the decreased neurosphere formation, proliferation, neurite outgrowth, and telomerase activity in cultured eNOS(-/-) SVZ neurospheres. SVZ explant cell migration also was significantly decreased in eNOS-/- mice compared with wild-type mice. These data indicate that eNOS is not only a downstream mediator for VEGF and angiogenesis but also regulates BDNF expression in the ischemic brain and influences progenitor cell proliferation, neuronal migration, and neurite outgrowth and affects functional recovery after stroke.
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PMID:Endothelial nitric oxide synthase regulates brain-derived neurotrophic factor expression and neurogenesis after stroke in mice. 1574 63


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