Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nestin, an intermediate filament protein, is known to be expressed in proliferating and provisional cells in the forming mammalian brain, disappearing on differentiation. The aim of the present work was to identify the morphological types and locations of cells regaining the ability to synthesize nestin after transient total brain ischemia in rats. Transient ischemia was found to be followed by the induction of nestin synthesis in astrocytes in the damaged area; these cells acquired structural features not characteristic of the adult brain, and these persisted in the long term. Nestin synthesis was also induced in proliferation-capable undifferentiated cells in the subventricular zone. The acquisition by astrocytes of some of the phenotypic features of immature glial cells, however, does not provide grounds for the notion that they were transformed into neural stem cells.
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PMID:Induction of nestin synthesis in rat brain cells by ischemic damage. 1819 79

STAT3 is a major signaling molecule for many neurotrophic factors but its direct role in the protection of neurons in response to stress has not been addressed. We have studied the role of STAT3 in protecting retinal neurons from damage induced by ischemia/reperfusion and glutamate excitotoxicity by using adenovirus constructs to introduce active, normal or inactive STAT3 into retinal ganglion cells in culture and cells of the ganglion cell layer in the intact retina. Transient ischemia/reperfusion was induced in adult CD1 mice by elevating the intraocular pressure to the equivalent of 120mmHg for 60min, followed by a return to normal pressure. The levels, activation and distribution of STAT3 protein were evaluated by Western blot and immunocytochemistry. A transient peak of STAT3 activation was seen at 24h post ischemia and a strong increase in STAT3 protein levels 24h later. The increase in levels of STAT3 was detected in both ganglion cell bodies and processes in the plexiform layers by immunocytochemistry. The time course of STAT3 increase was slower than the time course of ganglion cell death as measured by TUNEL assay. Intravitreal injection of NMDA led to peak increases in activated STAT3 and STAT3 at 12 and 24h post insult respectively. Purified RGCs were infected with recombinant wild-type STAT3, constitutively active and dominant negative forms of STAT3 adenoviruses or control empty virus and then treated with glutamate. Surviving infected cells were counted 24 and 48h later. Infection with constitutively active STAT3 gave substantial protection when compared to the other constructs. Similarly, intravitreal injection of constitutively active STAT3 adenovirus one day before ischemia-reperfusion resulted in a decreased neural cell death in the ganglion cell layer compared with GFP adenovirus control. Our results suggest that persistent activation of STAT3 by neurotrophic factors provides strong neuroprotection and will be an effective strategy in a number of chronic retinal diseases.
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PMID:STAT3 activation protects retinal ganglion cell layer neurons in response to stress. 1847 11

Changes in the extracellular space diffusion parameters during ischemia are well known, but information about changes during the postischemic period is lacking. Extracellular volume fraction (alpha) and tortuosity (lambda) were determined in the rat somatosensory cortex using the real-time iontophoretic method; diffusion-weighted magnetic resonance imaging was used to determine the apparent diffusion coefficient of water. Transient ischemia was induced by bilateral common carotid artery clamping for 10 or 15 mins and concomitant ventilation with 6% O(2) in N(2). In both ischemia groups, a negative DC shift accompanied by increased potassium levels occurred after 1 to 2 mins of ischemia and recovered to preischemic values within 3 to 5 mins of reperfusion. During ischemia of 10 mins duration, alpha typically decreased to 0.07+/-0.01, whereas lambda increased to 1.80+/-0.02. In this group, normal values of alpha=0.20+/-0.01 and lambda=1.55+/-0.01 were registered within 5 to 10 mins of reperfusion. After 15 mins of ischemia, alpha increased within 40 to 50 mins of reperfusion to 0.29+/-0.03 and remained at this level. Tortuosity (lambda) increased to 1.81+/-0.02 during ischemia, recovered within 5 to 10 mins of reperfusion, and was increased to 1.62+/-0.01 at the end of the experiment. The observed changes can affect the diffusion of ions, neurotransmitters, metabolic substances, and drugs in the nervous system.
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PMID:Extracellular diffusion parameters in the rat somatosensory cortex during recovery from transient global ischemia/hypoxia. 1854 60

Cerebral ischemia leads to neuronal damage in the hippocampus and cognitive decline. Reactive oxygen species play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Deprenyl, an irreversible monoamine-oxidase B inhibitor, has antioxidant and neuroprotective effects against reactive oxygen species. In the present study, the effect of deprenyl on spatial memory impairment, oxidative stress and apoptotic neuronal cell death following transient cerebral ischemia in rats was investigated. Transient ischemia was induced by occlusion of left common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 1 mg/kg deprenyl (n = 24) or equal volume of saline (n = 24) for 14 days before the experiment. Deprenyl treatment attenuated spatial memory deficits following ischemia-reperfusion as measured by the Morris water maze task. Deprenyl treatment elicited a significant decrease in lipid peroxidation and increase in superoxide dismutase activities in ischemic rat brains. The number of TUNEL-positive cells decreased significantly in deprenyl-treated group when compared with the control group. The results show that deprenyl reduces the ischemia-induced oxidative stress and thus prevents spatial memory deficits and apoptotic neuronal cell death when it is administered before ischemia-reperfusion.
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PMID:Protective effects of deprenyl in transient cerebral ischemia in rats. 1917 83

Cerebral ischemia leads to cognitive decline and neuronal damage in the hippocampus. Reactive oxygen species (ROS) play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Carnosine has both antioxidant and neuroprotective effects against ROS. In the present study, the effects of carnosine on oxidative stress, apoptotic neuronal cell death and spatial memory following transient cerebral ischemia in rats were investigated. Transient ischemia was induced by occlusion of right common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 250 mg/kg carnosine or saline 30 min prior to experiment. Determination of antioxidant enzyme activities was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed using an In Situ Cell Death Detection Kit. Carnosine treatment elicited a significant decrease in lipid peroxidation and increase in antioxidant enzyme activities in ischemic rat brains. The number of TUNEL-positive cells was decreased significantly in carnosine-treated group when compared with the ischemia-induction group. Carnosine treatment did not provide significant protection from ischemia induced deficits in spatial learning. The results show that carnosine is effective as a prophylactic treatment for brain tissue when it is administered before ischemia without affecting spatial memory.
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PMID:Carnosine attenuates oxidative stress and apoptosis in transient cerebral ischemia in rats. 1958 23

The beneficial effects of angiotensin II type 1 (AT1) receptor blockers (ARB) in cerebrovascular disease have been shown in clinical trials. However, the effects of ARBs vary based on their unique pharmacologic properties. In this study, we focused on telmisartan, a fat-soluble ARB with selective peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist activity, and investigated its effects on ischemic injury in cerebral vasculature using murine models of both transient and permanent focal ischemia. Analysis by triphenyltetrazolium-staining revealed that pre-treatment of mice with telmisartan reduced stroke volume 72 h after the transient ischemic insult in a dose-dependent manner, though such treatment did not reduce stroke volume due to permanent ischemia. Transient ischemia induced pro-inflammatory adhesion molecules, such as ICAM-1 and P-selectin in the ischemic region, and treatment with telmisartan diminished the expression of these adhesion molecules with diminished infiltration of inflammatory cells. The beneficial effect of telmisartan was attenuated, in part, by administration of a PPAR gamma antagonist. Treatment with valsartan (an ARB without PPAR gamma agonist activity) also decreased ischemic injury after transient ischemia, though to a lesser extent than telmisartan. Our findings indicate that telmisartan has a beneficial effect in a murine model of ischemia/reperfusion injury through blockade of AT1 receptors, and, in addition, due to a positive effect via its specific anti-inflammatory PPAR gamma agonist activity.
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PMID:Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. 2038

Delayed neuronal death following transient cerebral ischemia is mixed with apoptosis and necrosis, and the activation of microglia are activated after the ischemic insult. In the present study, we examined the long-term changes in neuronal degeneration and microglial activation in the gerbil hippocampal CA1 region after 5min of transient cerebral ischemia using specific markers for neuronal damage and microliosis. Transient ischemia-induced neuronal death was shown in CA1 pyramidal cells 4days after ischemia/reperfusion (I/R). However, neuronal degeneration of the pyramidal cells were observed up to 45days in the CA1 region after I/R. Microglial activation was also observed in the CA1 region after I/R. Isolectin B4- (IB4) immunoreactive ((+)) microglia appeared in the CA1 region 4days after I/R. On the other hand, ionized calcium-binding adapter molecule 1 (Iba-1)(+) microglia was markedly increased after I/R, and peaked at 15days after I/R. Thereafter, Iba-1 immunoreactivity was decreased with time-dependant manner in the ischemic CA1 region. These results indicate that neuronal degeneration of CA1 pyramidal cells may last about 45days in the CA1 region after ischemic damage, and microglial activation may be diverse according to their function, such as phagocytosis, after I/R.
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PMID:Long-term changes in neuronal degeneration and microglial activation in the hippocampal CA1 region after experimental transient cerebral ischemic damage. 2042 5

Stress has long been known to be a causative factor of various disease states. In this study, we investigated the effects of repeated restraint stress on platelet endothelial cell adhesion molecule-1 (PECAM-1), a very important mediator in inflammation, immunoreactivity and protein levels as well as neuronal damage, in the gerbil hippocampus after 5 minutes of transient cerebral ischemia. Transient ischemia-induced neuronal death was shown in CA1 pyramidal cells 4 days after ischemia/reperfusion. However, repeated restraint stress protected neuronal death induced by ischemic damage. In the ischemia-group, PECAM-1 immunoreactivity and its protein levels were significantly increased in all the hippocampal subregions 4 days after ischemia/reperfusion. However, PECAM-1 immunoreactivity and its protein levels did not change significantly in the hippocampus of the stress-ischemia-group compared to the sham-groups. These results indicate that repeated restraint stress protects neuronal damage induced by transient cerebral ischemia, and this may be associated with maintenance of PECAM-1levels.
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PMID:Effects of repeated restraint stress on platelet endothelial cell adhesion molecule-1 immunoreactivity and protein levels in the gerbil hippocampus after transient cerebral ischemia. 2119 5

Depression is a frequent but often unrecognized and under treated complication of stroke that has scarcely been investigated in animal models particularly regarding treatment issues. Using the Forced Swim Test (FST) and testing spontaneous motor activity, we studied whether a transient focal cerebral ischemia modifies mice behaviours and antidepressant drug effects. We first evaluated whether FST realized 2 days or 1 week after brain reperfusion may be routinely used in male Swiss mice previously submitted to a 15, 30 or 60-min transient occlusion of the right middle cerebral artery. We then evaluated behavioural changes up to 5 weeks in mice previously submitted to a 15-min ischemia. Behaviours according to the administration of imipramine or fluvoxamine at 1 and 5 weeks after a 15-min ischemia were finally evaluated. Transient ischemia was associated with a decrease in immobility in the FST performed 2 days after reperfusion while no changes were observed in 1 and 5 weeks post-ischemia groups. Changes were related neither to brain ischemia duration nor to infarct volume. At both 1 and 5 weeks after brain ischemia, a dramatic decrease in the antidepressant response to imipramine related to a decrease in climbing behaviour was observed while the effects of fluvoxamine were improved through an increase in both climbing and swimming. Behaviours in the FST were unrelated to any spontaneous motor activity changes. Responses to anti-depressant drugs are strongly modified in mice previously submitted to brain ischemia. Present results underline that not all antidepressant drugs are appropriate after ischemic stroke.
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PMID:Brain ischemia changes the long term response to antidepressant drugs in mice. 2123 93

Stem cells have the ability to self renew and are therefore a good source for cell therapy following ischemia. In this study, we transplanted adult rat neural stem cells (NSCs) by lumbar puncture (LP) to investigate whether these cells can migrate and differentiate into neurons or glial cells, thereby improving functional outcome in cerebral ischemia. Transient ischemia was induced in adult rats (n=16) for 1h. Three days after the induction of ischemia, NSCs obtained from the subventricular zone of adult rats were injected into ischemic animals (n=8) by LP at the level of L6-S1. Improved recovery of the coordination of movement on the 1st, 7th, 14th, 21st and 28th days after the injury was examined by the Rotarod test and compared with non-transplanted ischemic animals (n=8). The presence of NSCs in the brain tissue of the animals was examined by immunohistofluorscence and immunohistochemical techniques. The coordination of movement in ischemic animals that received neural stem cells was improved significantly (P<0.05) compared with untreated ischemic animals. Cells labeled with PKH26 were observed in the ischemic area of brain tissue sections. The alkaline phosphatase test and immunohistochemical techniques demonstrated a gathering of NSCs in the lateral ventricle. A number of cells which expressed neuronal and astrocytic cell markers had migrated from the lateral ventricle to the subjacent brain parenchyma. NSCs injected by LP were able to migrate to the ischemic tissue and differentiate into neural-like cells. These differentiated cells may have improved the coordination in movement in the ischemic animals injected with NSCs.
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PMID:Investigating the effects of adult neural stem cell transplantation by lumbar puncture in transient cerebral ischemia. 2133 15


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