Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an immunoblotting technique, we investigated changes in the concentrations of microtubule-associated protein 2, 200-kDa neurofilament, tubulin, myelin-associated glycoprotein, and 2':3'-cyclic nucleotide 3'-phosphodiesterase in the brains of 40 rats following occlusion of the left middle cerebral artery or sham operation. Compared with those 4 hours after surgery, concentrations of all proteins decreased significantly in the left hemisphere 3 days after surgery (p less than 0.01). Microtubule-associated protein 2 was the most susceptible to ischemia, and its mean +/- SEM concentration decreased to 23 +/- 9.4% of that in concurrent sham-operated controls. Degradation products of microtubule-associated protein 2 and myelin-associated glycoprotein were detected on the blots. Furthermore, in the contralateral hemisphere (where calpain might be activated), concentrations of these two proteins decreased to 57 +/- 12.0% and 83 +/- 4.3% of those in concurrent sham-operated controls, respectively, 3 days after surgery. Changes in the concentrations of cerebral proteins in the contralateral hemisphere are important for understanding clinical symptoms not attributable solely to the ipsilateral lesion following a focal cerebral stroke.
Stroke 1990 Jun
PMID:Changes in the concentrations of cerebral proteins following occlusion of the middle cerebral artery in rats. 211 75

A coiled stainless steel wire clip was made that allowed us to chronically reduce cerebral blood flow in Mongolian gerbils. After 6 weeks of reduced cerebral blood flow in 15 experimental gerbils, we evaluated their learning ability and found it to be impaired relative to that in 15 control gerbils. Eight weeks after surgery, regional cerebral blood flow in the parietal cortex measured by the hydrogen clearance method in the experimental gerbils was 73-76% of that in the control gerbils. Light microscopy showed minimal histologic changes in the brains of the experimental gerbils. Concentrations of brain proteins analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that among water-soluble brain proteins, the concentrations of cytoskeletal proteins (microtubule-associated protein 2, calspectin, and clathrin) declined in the experimental gerbils. In particular, the concentration of microtubule-associated protein 2 declined significantly. Our findings show that the reduction of cerebral blood flow via carotid stenosis impairs the learning behavior in gerbils, with an associated decrease in the concentration of microtubule-associated protein 2. We believe that Mongolian gerbils with chronically reduced cerebral blood flow are a useful animal model of chronic brain hypoperfusion.
Stroke 1990 Aug
PMID:Learning impairment and microtubule-associated protein 2 decrease in gerbils under chronic cerebral hypoperfusion. 238 2

We have previously demonstrated that transient cerebral ischemia induces marked decreases in concentrations of cytoskeletal proteins and have suggested putative involvement of calpain in the decrease of microtubule-associated protein 2 (MAP2) content. We examine the effect of nilvadipine, a new calcium channel blocker, on protein degradation in gerbil brains after 5 minutes of bilateral carotid artery occlusion and compare this effect with those of nimodipine and nicardipine. By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day. MAP2 content was also depleted in vitro when normal nonischemic brain extract was incubated with calcium, but this degradation was not inhibited by the calcium channel blockers. Our results suggest that calcium channel blockers do not act directly on calpain but act at the calcium channels of neurons and may suppress activation of the enzyme and attenuate ischemic degradation of cytoskeletal protein. We found nilvadipine to be the most potent drug among those studied, and we believe it could be useful for the treatment of cerebral ischemia.
Stroke 1989 Jan
PMID:Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins. 291 39

To examine the therapeutic effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane) on neuronal ischemia-reperfusion injury, we evaluated the neurological score in gerbils subjected to unilateral common carotid occlusion. Using the neurological score method, we selected animals which showed stroke symptoms without seizures, because seizure activity can modify the neurological outcome. Just after the clip removal following 30 min of ischemia, 0.2 ml of either vehicle (0.9% saline, n = 10) or bifemelane (25 mg/kg, n = 10) was administered intraperitoneally. Then, the neurological score and the maximum inclination at which the gerbil could maintain its equilibrium were recorded at 5, 10, and 30 min, and 1, 2, 3, 6, and 24 hr after the insult. Animals were then decapitated and their brains were processed for immunohistochemical investigation. Treatment with bifemelane after reperfusion significantly improved the neurological score and motor function. Immunohistochemistry using an antibody for microtubule-associated protein 2 clearly demonstrated preservation of staining especially in the caudate-putamen in the animals treated with bifemelane. The present findings suggest a beneficial effect of bifemelane on neuronal ischemia-reperfusion injury, which may be common after cerebral ischemia.
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PMID:Therapeutic effect of bifemelane on unilateral cerebral ischemia in gerbils. 760 10

We evaluated the influence of an acute hypoxic-ischemic insult on the neuronal dendritic cytoskeletal protein microtubule-associated protein 2 (MAP2) in the immature rat brain. Studies were performed using a well-characterized perinatal rodent stroke model, in which unilateral ischemic forebrain injury was induced in 7-day-old rats by right carotid artery ligation, followed by 3 h exposure to 8% oxygen. Changes in the neuroanatomic distribution of MAP2 in the first 48 h after injury were evaluated by immunocytochemistry with a monoclonal mouse anti-MAP2 antibody. The distribution of MAP2 immunoreactivity was markedly disrupted in the lesioned hippocampus; prominent reductions in MAP2 immunostaining evolved concurrently in lesioned cortex, caudate and thalamus. These data demonstrate that at this developmental stage, MAP2 immunocytochemistry provides a sensitive indicator of the distribution and severity of hypoxic-ischemic neuronal injury.
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PMID:Hypoxic-ischemic injury acutely disrupts microtubule-associated protein 2 immunostaining in neonatal rat brain. 872 54

Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. To investigate the correlation of brain stem damage with various cause of respiratory disorders, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) were examined using immunohistochemical technique. Based on the cause of death, the forensic autopsy cases were divided into 5 groups as follows. Group I: hanging, ligature strangulation and manual strangulation, Group II: smothering and choking, Group III: drowning, Group IV: respiratory failure, control group: heat stroke and sun stroke. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Three nuclei showed no obvious morphological changes in all examined groups. However, in case of asphyxia (Group I to III), neurons in HN were positively stained with both HSP70 and c-Fos antibodies. This may indicate that the occlusion of upper airway results in the neuronal damage of HN without their morphological changes. Positive staining of HSP70 and c-Fos in IO was more frequently observed in Group III than other 4 groups. Since IO is involved in maintaining body balance which is often disturbed by drowning, it seems possible that neuronal damage in IO observed in drowning may be related to the disturbance of body balance. These observations indicate that immunohistochemical study on the damage to neurons in brain stem nuclei can provide useful information for determining the cause of death.
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PMID:[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. I. Various cases of asphyxia and respiratory disorder]. 1033 83

Apolipoprotein (apo) E isoforms are key determinants of susceptibility to Alzheimer's disease. The apoE4 isoform is the major known genetic risk factor for this disease and is also associated with poor outcome after acute head trauma or stroke. To test the hypothesis that apoE3, but not apoE4, protects against age-related and excitotoxin-induced neurodegeneration, we analyzed apoE knockout (Apoe-/-) mice expressing similar levels of human apoE3 or apoE4 in the brain under control of the neuron-specific enolase promoter. Neuronal apoE expression was widespread in the brains of these mice. Kainic acid-challenged wild-type or Apoe-/- mice had a significant loss of synaptophysin-positive presynaptic terminals and microtubule-associated protein 2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus. Expression of apoE3, but not of apoE4, protected against this excitotoxin-induced neuronal damage. ApoE3, but not apoE4, also protected against the age-dependent neurodegeneration seen in Apoe-/- mice. These differences in the effects of apoE isoforms on neuronal integrity may relate to the increased risk of Alzheimer's disease and to the poor outcome after head trauma and stroke associated with apoE4 in humans.
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PMID:Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration. 1036 21

Stroke is the major cause of adult brain dysfunction. In an experimental approach to evaluate the possible beneficial effects of administration of neurotrophic factors in stroke, we have used a model of distal middle cerebral artery (MCA) occlusion in adult rats. In this model, we found: (1) a permanent reduction of brain-derived neurotrophic factor (BDNF) and its full-length receptor, TrkB, in the infarcted core; (2) a transient increase in BDNF immunoreactivity in the internal region of the border of the infarct (penumbra area) at 12 h after MCA occlusion; (3) increased truncated TrkB immunoreactivity in astrocytes surrounding the area of the infarction; and (4) increased full-length TrkB immunoreactivity in scattered neurons, distant from the infarct, in ipsilateral and contralateral cortices at 24 and 48 h after MCA occlusion. We next studied the regulation of TrkB expression by BDNF, after ischemia, and its neuroprotective effects in vivo. In control non-ischemic rats, grafting of mock- or BDNF-transfected fibroblasts (F3A-MT or F3N-BDNF cell lines, respectively) in the medial part of the somatosensory cortex increased truncated TrkB immunoreactivity in neighboring astrocytes. Grafting alone also increased full-length TrkB in the vicinity of the mock graft (at 24 and 48 h) and the BDNF-grafted graft (at 4 days). Interestingly, ischemic animals grafted with the mock-transfected cell line did not show any further regulation of TrkB receptors. However, ischemic animals grafted with the BDNF cell line showed an up-regulation of full-length TrkB expression in neurons located in the internal border of the infarct. Analysis of nuclear DNA fragmentation in situ, combined with microtubule-associated protein 2 immunohistochemistry, revealed that most cells dying in the borders of the infarct (penumbra area) at 48 h following MCA occlusion were neurons. No differences in the infarct size were found between MCA occluded, mock-transfected MCA-occluded, and BDNF-transfected MCA-occluded rats. Moreover, cell death was similar in nongrafted and mock-grafted rats subjected to MCA occlusion. However, the number of cells with nuclear DNA breaks was significantly reduced in the penumbra area close to the BDNF graft in ischemic rats. Thus, our results show that BDNF specifically up-regulates its full-length TrkB receptor in cortical neurons of the penumbra area and prevents their death in an in vivo model of focal ischemia.
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PMID:Brain-derived neurotrophic factor reduces cortical cell death by ischemia after middle cerebral artery occlusion in the rat. 1130 22

Although stem cell-based treatments for stroke and other neurodegenerative diseases have advanced rapidly, there are still few clinical treatments available. In this study, rats receiving intracerebral peripheral blood hematopoietic stem cell (CD34+) (PBSC) transplantation showed much more improvement in neurological function after chronic cerebral ischemia in comparison with vehicle-treated control rats. Using laser-scanning confocal microscopy, implanted PBSCs were seen to differentiate into glial cells [GFAP+ (glial fibrillary acidic protein-positive)], neurons [Nestin+, MAP-2+ (microtubule-associated protein 2-positive), Neu-N+ (neuronal nuclear antigen-positive)], and vascular endothelial cells [vWF+ (von Willebrand factor-positive)], thereby enhancing neuroplastic effects in the ischemic brain. Cortical neuronal activity, as evaluated by 1H-MRS (proton magnetic resonance spectroscopy), also increased considerably in PBSC-treated rats compared with a vehicle-treated control group. In addition, PBSC implantation promoted the formation of new vessels, thereby increasing the local cortical blood flow in the ischemic hemisphere. These observations may be explained by the involvement of stem cell-derived macrophage/microglial cells, and beta1 integrin expression, which might enhance this angiogenic architecture over the ischemic brain. Furthermore, quantitative reverse transcription-PCR analysis showed significantly increased modulation of neurotrophic factor expression in the ischemic hemisphere of the PBSC-transplanted rats compared with vehicle-treated control rats. Thus, intracerebral PBSC transplantation might have potential as a therapeutic strategy for treating cerebrovascular diseases.
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PMID:Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. 1657 51

In this study, we investigated the effects of electroacupuncture (EA) on ischemia-induced neurogenesis in the striatum of adult rat brains with a 30-minute middle cerebral artery occlusion. Injection of bromodeoxyuridine (BrdU, 30 mg/kg, i.p., cell proliferation marker) and 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3',3',3' -tetramethylindocarbo-cyanine (DiI, 1 microg/ microl, i.c.v, lipophilic neuronal tracer) combined with multiple fluorescence immunostaining were used to determine whether the proliferated cells were newly generated neurons and where they originated from in the brain. We demonstrated that EA treatment (60 Hz 1 s and 2 Hz 3 s alternately at an intensity of 10 mA for 20 min on "Fengfu", GV.16 and "Jinsuo", GV.8) enhanced stroke-induced striatal neurogenesis in rat brains as follows: 1) EA increased the number of BrdU+ cells, indicating that it activates cell proliferation; 2) EA increased BrdU+/CRMP-4(+) (collapsing response mediated protein-4, immature neuron marker) and BrdU+/MAP-2(+) (microtubule-associated protein 2, mature neuron marker) cells, suggesting that it facilitates neurogenesis and maturation of newly generated neurons; 3) EA expanded the distribution of DiI-stained cells in the striatum. Moreover, most BrdU+/CRMP-4(+) or BrdU+/MAP-2(+) cells in the striatum were observed DiI+ staining. Thus, the results suggest that striatal newborn neurons mainly migrate from the cells lining ventricle. Therefore, we conclude that EA can improve neuronal regeneration, newborn neuron migration and their maturation in the striatum of adult rat brains after stroke.
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PMID:Electroacupuncture enhances striatal neurogenesis in adult rat brains after a transient cerebral middle artery occlusion. 1661 87


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