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 stroke-prone spontaneously hypertensive rats with permanent occlusion of the middle cerebral artery (MCA), we investigated whether the secondary thalamic degeneration following cortical infarction is related to apoptosis, and whether the protein synthesis inhibitor cycloheximide (CHX) ameliorates this degenerative process. TdT-mediated dUTP-biotin nick end labeling (TUNEL staining) revealed a distinct pattern of nuclear staining in many ventroposterior (VP) thalamic nucleus neurons on the lesioned side at 1 week after MCA occlusion. In rats with a single or continuous intraventricular infusion of CHX, starting just after brain ischemia, in the VP thalamic neurons were significantly more numerous than those in the thalamic nucleus of rats with vehicle infusion at 1 week after MCA occlusion. However, at 2 weeks after MCA occlusion, the numbers of VP thalamic neurons were similar in the CHX- and vehicle-treated groups. These findings suggest that the secondary thalamic degeneration following cortical infarction is an event reminiscent of apoptosis and that CHX prevents the secondary thalamic neuronal death transiently.
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PMID:Protein synthesis inhibitor transiently reduces neuronal death in the thalamus of spontaneously hypertensive rats following cortical infarction. 932 31

Using stroke-prone spontaneously hypertensive (SH-SP) rats with permanent occlusion of the middle cerebral artery (MCA), we investigated the expression of wild type p53 (wt-p53) protein and the occurrence of DNA fragmentation in cerebral neurons after ischemia. Three days following MCA occlusion, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL staining) revealed a distinct pattern of nuclear staining in many neurons around the ischemic core. On the lesioned side of the cerebral cortex one day after MCA occlusion, wt-p53 immunoreactivity was observed specifically in the cortical neurons, in the same regions as the TUNEL staining. Mutant type p53 (mt-p53) immunoreactivity was not observed at any time following MCA occlusion. These findings suggest that wt-p53 dependent cell death of cortical neurons occurred in the ischemic periphery following cerebral ischemia and that this pathway for the induction of cell death may play an important role in the exaggeration of cerebral ischemic injury.
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PMID:Increase in p53 protein expression following cortical infarction in the spontaneously hypertensive rat. 1043 86

The present study investigates the induction of neurogenesis, reduction of apoptosis, and promotion of basic fibroblast growth factor (bFGF) expression as possible mechanisms by which treatment of stroke with bone marrow stromal cells (MSCs) improves neurological functional recovery. Additionally, for the first time, we treated cerebral ischemia in female rats with intraveneous administration of MSCs. Female rats were subjected to 2 hr of middle cerebral artery occlusion (MCAo), followed by an injection of 3 x 10(6) male (for Y chromosome labeling) rat MSCs or phosphate-buffered saline (PBS) into the tail vein 24 hr after MCAo. All animals received daily injection of bromodeoxyuridine (BrdU; 50 mg/kg, i.p.) for 13 days after treatment for identification of newly synthesized DNA. Animals were sacrificed at 14 days after MCAo. Behavioral tests (rotarod and adhesive-removal tests) were performed. In situ hybridization, immunohistochemistry, and terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) were performed to identify transplanted MSCs (Y chromosome), BrdU, bFGF, and apoptotic cells in the brain. Significant recovery of behavior was found in MSC-treated rats at 7 days in the somatosensory test and at 14 days in the motor test after MCAo compared with control, PBS-treated animals (P<.05). MSCs were found to survive and preferentially localize to the ipsilateral ischemic hemisphere. Significantly more BrdU-positive cells were located in the subventricular zone (P<.05), and significantly fewer apoptotic cells and more bFGF immunoreactive cell were found in the ischemic boundary area (P<.05) of MSC-treated rats than in PBS-treated animals. Here we demonstrate that intravenously administered male MSCs increase bFGF expression, reduce apoptosis, promote endogenous cellular proliferation, and improve functional recovery after stroke in female rats.
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PMID:Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. 1294 3

Considerable evidence is accumulating to suggest that in vivo formation of free radicals in the brain, such as peroxynitrite (ONOO-), and programmed cell death (i.e. apoptosis) play important roles in neurodegeneration and stroke. However, it is not known whether ONOO- can induce apoptosis in cerebral vascular smooth muscle cells (CVSMCs). The present study was designed to determine whether or not canine CVSMCs undergo apoptosis following treatment with ONOO-. Direct exposure of canine CVSMCs to ONOO- induced apoptosis in a concentration-dependent manner, as confirmed by means of fluorescence staining, TdT-mediated dUTP nick-end labeling and comet assays. Peroxynitrite treatment resulted in an elevation of [Ca2+]i in the CVSMCs. Peroxynitrite-induced apoptosis may thus be brought about by activation of Ca2+-dependent endonucleases. Although the precise mechanisms by which peroxynitrite induces apoptosis need to be further investigated, the present findings could be used to suggest that ONOO- formation in the brain may play important roles in neurodegenerative processes and strokes via detrimental actions on cerebral microvessels and blood flow.
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PMID:Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes. 1455 Sep 22

Recent data suggest that the incidence of focal cerebral ischemia (FCI) and stroke is higher than previously recognized and could account for a large proportion of brain lesions in the preterm and full term neonate. Therefore, it is critically important to develop an appropriate model of FCI in neonatal animals. We describe here a modified model of permanent FCI in rat pups at postnatal day-7 (P7). To produce permanent FCI, a suture embolus with different diameters (180-220 microm) was inserted into the left common carotid artery (CCA) of the pups with different weight (14-19 g). Then the suture embolus was advanced to the middle cerebral artery (MCA) to produce its occlusion. The success of vascular occlusion was evaluated by imaging the ischemic territory on serial brain sections with carbon black staining immediately after permanent FCI. The consistent cerebral infarction was confirmed by 2,3,5-triphenyltetrazolium chloride (TTC) staining 24 h after permanent FCI. Terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphospate-biotin nick end labeling (TUNEL) staining showed cell death with TUNEL labeling in the ischemic areas, which is one of the features of apoptosis. The present model opens the way for advanced pathophysiological studies of FCI in neonates.
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PMID:A reproducible experimental model of focal cerebral ischemia in the neonatal rat. 1517 89

Poly(ADP-ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3-aminobenzamide (3-AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3-AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague-Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague-Dawley rats were used for sham operation. 3-AB was administered to 85 rats 10 min before the occlusion [3-AB group (n = 85) vs. control group without 3-AB (n = 85)]. Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end-labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP-ribose) polymer (PAR), cleaved caspase-3, CD11b, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), phospho-Akt (pAkt) and phospho-glycogen synthase kinase-3 (pGSK-3) were compared in the peri-infarcted region of the 3-AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3-AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL-positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase-3, CD11b, ICAM-1 and COX-2 were significantly reduced, while the IRs of pAkt and pGSK-3 were increased. These results suggest that 3-AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.
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PMID:The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals. 1535 13

Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with stroke and neurotrauma. The aim of our study was to evaluate the therapeutic efficacy of in vivo inhibition of PARP in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration (measured as an increase in myeloperoxidase activity), and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated UTP end labeling coloration). Infiltration of spinal cord tissue with neutrophils was associated with a marked increase in immunoreactivity for poly(ADP-ribose) (PAR), index of PARP activation, in the spinal cord tissue. These inflammatory events were associated with the activation of nuclear factor-kappaB (NF-kappaB) at 4 h after spinal cord damage. Treatment of the mice with the PARP inhibitors 3-aminobenzamide (3-AB) or 5-aminoisoquinolinone (5-AIQ) significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score), 2) PAR formation, 3) neutrophil infiltration, and 4) apoptosis. Treatment with these PARP inhibitors also reduced DNA binding of NF-kappaB and inhibitory kappaB degradation. In a separate set of experiments, we have also demonstrated that PARP inhibitors significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with PARP inhibitors reduces the development of inflammation and tissue injury events associated with spinal cord trauma.
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PMID:Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways and secondary damage in experimental spinal cord trauma. 1545 94

Erythropoietin (Epo) plays a central role in erythropoiesis but also has neuroprotective properties. Recently, Epo-related neuroprotective studies used a hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent cause of neonatal brain injury. We report on the effects of Epo treatment given after focal stroke and its potential neuroprotective mechanisms in postnatal day 7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle cerebral artery. The experimental groups included sham operation, FCI plus vehicle, and FCI plus Epo. In the Epo-treated group, pups received a single intraperitoneal injection of 1000 U/kg 15 min after FCI or three injections of 100, 1000, or 5000 U/kg, starting at 15 min and repeated at 1 and 2 d after FCI. Epo treatment produced significant reductions in the mean infarct area and volume at 1 and 3 d after FCI, demonstrated by 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining showed a markedly reduced number of TUNEL-positive cells in the Epo-treated group when compared with the vehicle control 3 d after FCI (p<0.01). The most effective dose after FCI was 1000 U/kg for 3 d. Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-kappaB expression. In conclusion, Epo given after FCI in neonatal rats provides significant neuroprotection, mediated possibly by activation of the Janus kinase-signal transducer and activator of transcription-Bcl-xL signaling pathways.
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PMID:Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. 1571 73

The expression of BAX in carotid atherosclerosis and its regulation is far from defined. Objectives To investigate BAX expression in stable/fibrous and instable/vulnerable carotid plaque and its clinical significance. Methods Twenty-five cases of carotid plaque specimens obtained from endarterectomy were divided into two groups, stable/fibrous 14 cases, vulnerable/instable 11 cases; aortic artery and its branches from hepatic transplantation donors 6 case as control. The expression of proapoptotic BAX was detected by immunohistochemistry (IHC), in situ hybridization(ISH) and in situ TdT dUTP nick end labeling (TUNEL). Results Five cases of BAX ( + ) were detected by ICH and ISH, 4 case of TUNEL ( + ) were detected by TUNEL in stable/fibrous carotid plaque , while 10 cases were BAX ( + )by IHC(P < 0.05) , 11 cases by ISH and 9 cases by TUNEL were detected in instable/vulnerable carotid plaque ( P < 0.01 ), respectively. The intensity of BAX ( + ) cells by IHC and ISH was (8.63 +/- 2.62) and (10.32 +/- 3.12) in fibrous plaques, whereas (122 +/- 21.64) and (152 +/- 23.35) in vulnerable plaques, respectively. No expression of BAX was found in controlled group. Conclusion The higher expression of Bax in vulnerable carotid plaque may be one mechanism in molecular pathogenesis of carotid atherosclerosis which affect plaque stability and be the cause of higher incidence of stroke than fibrous carotid plaques, the regulation of BAX expression in different stage of atherosclerosis may provide targets in gene therapy for carotid atherosclerosis.
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PMID:Apopotic gene Bax expression in carotid plaque. 1768 41

Preclinical and clinical studies have demonstrated that a free radical scavenger edaravone has neuroprotective effects on ischemic stroke but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the Fas/FasL signaling pathway. Transient focal ischemia in rats was induced for 2 hours by middle cerebral artery occlusion (MCAO). After reperfusion rats were treated i.v. with either edaravone or physiological saline. The expression of Fas-associated death domain protein (FADD), death-associated protein (Daxx) and caspase-8 was examined by immunohistochemistry. The mRNA levels for FADD and Daxx by reverse-transcriptase PCR (RT-PCR) and apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Neurological scores and infarction volumes were also evaluated. Edaravone significantly improved the neurological outcome (p<0.05) and reduced the total infarct volumes (p<0.05), compared with saline control. In addition, edaravone-treatment significantly reduced the number of TUNEL-positive cells (p<0.01), reduced expression levels of FADD, Daxx and caspase-8 immunoreactivity (p <0.05 approximately 0.01), and decreased mRNA levels of FADD and Daxx (p<0.05 approximately 0.01) within the peri-infarct area. We conclude that edaravone may protect ischemic neurons from apoptosis via suppressing the gene expression of the Fas/FasL signaling pathway.
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PMID:Edaravone neuroprotection effected by suppressing the gene expression of the Fas signal pathway following transient focal ischemia in rats. 1796 39


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