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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal apoptosis is important in the developmental sculpting of a normal nervous system and also in the loss of neurons caused by neurodegenerative disease, ischemia or trauma. In a developing embryo, exquisite mechanisms of regulation exist to balance factors that control neuronal birth and death within a given neuronal group, so that sufficient neurons develop and survive to elicit normal function. Postnatally, the only part of the mammalian nervous system where many of these regulatory balance mechanisms are retained is the olfactory epithelium (OE). During the last 30 years, researchers investigating olfactory receptor neuron cellular and developmental biology have focussed on the regeneration of the neuronal population within the olfactory neuroepithelium, following the induced death of the mature neuronal population. This body of work has thus far overshadowed the equally important and intrinsically linked phenomenon of the death of mature olfactory receptor neurons, which is required to initiate regeneration. The purpose of this review is to reveal what has been established about the different forms of cell death that can occur in neurons of the olfactory epithelium, and highlight the identified pro- and anti-apoptotic pathways that control the normal and induced turnover of olfactory receptor neurons.
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PMID:Apoptosis in the mature and developing olfactory neuroepithelium. 1220 99

The purpose of this study was to investigate the effect of (3S)-7-chloro-3-[2-((1R)-1-carboxyethoxy)-4-aminomethylphenyl]aminocarbonylmethyl-1,3,4,5-tetrahydrobenz[c,d]indole-2-carboxylic acid hydrochloride (SM-31900), an antagonist with high selectivity and affinity for the NMDA receptor glycine-binding site, on the cerebral infarct volume in a permanent middle cerebral artery occlusion (MCAo) model, which was constructed by electrocoagulation of a unilateral middle cerebral artery distal to the olfactory tract using spontaneously hypertensive rats (SHRs). To investigate the dose-response characteristics and the therapeutic time window of SM-31900 in this MCAo model, we conducted three experiments, in which the administration of SM-31900 was started 5min (experiment I), 30min (experiment II), or 60min (experiment III) after MCAo, respectively. In all the studies, SM-31900 was administered by intravenous bolus injection followed by continuous intravenous infusion to obtain a steady-state level of this compound in blood immediately after its administration. The treatment with SM-31900 was continued until 24h after MCAo, at which time the cerebral infarct volume was measured. In experiment I, SM-31900 significantly reduced the infarct volume by 37% at a dosage of 0.38mg/kg bolus followed by 1.5mg/kg/h continuous infusion (0.38mg/kg+1.5mg/kg/h). In experiment II, the neuroprotective effect of SM-31900 was also significant, with a 25% reduction in infarct volume at a dosage of 0.38mg/kg+1.5mg/kg/h, and a 40% reduction at 1.5mg/kg+6.0mg/kg/h. Furthermore, even in experiment III, SM-31900 exerted a significant neuroprotective effect, with a 20% reduction at 1.5mg/kg+6.0mg/kg/h. These studies revealed that SM-31900 can exert a neuroprotective effect when it is administered up to at least 60min after the onset of ischemia in the MCAo model, an animal model of stroke, indicating that SM-31900 is a good candidate for treating acute brain ischemia.
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PMID:SM-31900, a novel NMDA receptor glycine-binding site antagonist, reduces infarct volume induced by permanent middle cerebral artery occlusion in spontaneously hypertensive rats. 1251 20

The stage of neurogenesis can be divided into three steps: proliferation, migration, and differentiation. To elucidate their detailed relations after ischemia, the three steps were comprehensively evaluated, in the subventricular zone (SVZ) through the rostral migratory stream (RMS) to the olfactory bulb (OB), in adult gerbil brain after 5 minutes of transient forebrain ischemia. Bromodeoxyuridine (BrdU), highly polysialylated neural cell adhesion molecule (PSA-NCAM), neuronal nuclear antigen (NeuN), and glial fibrillary acidic protein (GFAP) were used as markers for proliferation, migration, and differentiation, respectively. The number of BrdU-labeled cells that coexpressed PSA-NCAM and the size of PSA-NCAM-positive cell colony increased in the SVZ with a peak at 10 d after transient ischemia. In the RMS, the number of BrdU-labeled cells that coexpressed PSA-NCAM increased, with a delayed peak at 30 d, when the size of RMS itself became larger and the number of surrounding GFAP-positive cells increased. In the OB, BrdU + NeuN double positive cells were detected at 30 and 60 d. NeuN staining and terminal deoxynucleotidyl dUTP nick-end labeling staining showed no neuronal cell loss around the SVZ, and in the RMS and the OB after transient ischemia. These findings indicate that transient forebrain ischemia enhances neural stem cell proliferation in the SVZ without evident neuronal cell loss, and has potential neuronal precursor migration with activation of GFAP-positive cells through the RMS to the OB.
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PMID:Temporal profile of stem cell division, migration, and differentiation from subventricular zone to olfactory bulb after transient forebrain ischemia in gerbils. 1262 8

We investigated the fate of proliferating cells in the adult monkey brain after global ischemia. We used the thymidine analogue bromodeoxyuridine (BrdU) to label S-phase cells and their progeny in Japanese macaques subjected to global cerebral ischemia for 20 min or to a sham operation. Subsequently, newly generated cells were identified by BrdU immunohistochemistry, and their immunophenotype was determined quantitatively, using specific markers. The ischemic insult significantly increased the number of proliferating cells in the hippocampus and temporal neocortex, where the majority BrdU-labeled cells expressed markers for microglia (Iba1, CD68, and Ham56) or astrocytes (S-100beta and glial fibrillary acidic protein [GFAP]). In contrast, the proliferation level in the parahippocampal region remained unchanged. This discrepancy prompted us to investigate the postischemic response in the olfactory bulb, a well-known site of adult cell generation that is anatomically distant from the above-mentioned regions but that is also subjected to the global ischemic insult. The olfactory bulb contained clusters of proliferating cells expressing markers for neural (Musashi1 and Nestin) and/or neuronal (class III beta-tubulin) progenitors; these were immunophenotypically distinct from other cell types. Their number and distribution were unaltered by ischemia. Our results demonstrate that cell proliferation and differentiation in the adult macaque brain and olfactory bulb are differentially affected by a common insult.
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PMID:Differential proliferative response in the postischemic hippocampus, temporal cortex, and olfactory bulb of young adult macaque monkeys. 1267 28

We investigated spatial and temporal alterations of calbindin D-28k (CB) immunoreactivity in the gerbil main olfactory bulb after transient ischemia-reperfusion. In sham-operated animals, CB-immunoreactive (IR) neurons were found in the periglomerular layer, external plexiform layer and granule cell layer. At 1-4 days after ischemic insult, the number of CB-IR neurons significantly increased. This result suggests that the increased CB may buffer the intracellular calcium at an early time point after the ischemic insult. In contrast, 10-30 days after the ischemic insult, the number of CB-IR neurons significantly decreased as compared to sham-operated animals. This result suggests that a malfunction in olfactory process may have occurred in the olfactory bulb at a later time point after the ischemic insult.
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PMID:Chronological alterations of calbindin D-28k immunoreactivity in the gerbil main olfactory bulb after ischemic insult. 1270 42

The immature brain is more resistant to hypoxia/ischemia than the mature brain. Although chronic hypoxia can induce adaptive-changes on the developing brain, the mechanisms underlying such adaptive changes are poorly understood. To further elucidate some of the adaptive changes during postnatal hypoxia, we determined the activities of four enzymes of glucose oxidative metabolism in eight brain regions of hypoxic and normoxic rats. Litters of Sprague-Dawley rats were put into the hypoxic chamber (oxygen level maintained at 9.5%) with their dams starting on day 3 postnatal (P3). Age-matched normoxic rats were use as control animals. In P10 hypoxic rats, lactate dehydrogenase (LDH) activity in cerebral cortex, striatum, olfactory bulb, hippocampus, hypothalamus, pons and medulla, and cerebellum was significantly increased (by 100%-370%) compared to those in P10 normoxic rats. In P10 hypoxic rats, hexokinase (HK) activity in hypothalamus, hippocampus, olfactory bulb, midbrain, and cerebral cortex was significantly decreased (by 15%-30%). Neither alpha-ketoglutarate dehydrogenase complex (KGDHC, which is believed to have an important role in the regulation of the tricarboxylic acid [TCA] cycle flux) nor citrate synthase (CS) activity was significantly decreased in the eight regions of P10 hypoxic rats compared to those in P10 normoxic rats. In P30 hypoxic rats, LDH activity was only increased in striatum (by 19%), whereas HK activity was only significantly decreased (by 30%) in this region. However, KGDHC activity was significantly decreased in olfactory bulb, hippocampus, hypothalamus, cerebral cortex, and cerebellum (by 20%-40%) in P30 hypoxic rats compared to those in P30 normoxic rats. Similarly, CS activity was decreased, but only in olfactory bulb, hypothalamus, and midbrain (by 9%-21%) in P30 hypoxic rats. Our results suggest that at least some of the mechanisms underlying the hypoxia-induced changes in activities of glycolytic enzymes implicate the upregulation of HIF-1. Moreover, our observation that chronic postnatal hypoxia induces differential effects on brain glycolytic and TCA cycle enzymes may have pathophysiological implications (e.g., decreased in energy metabolism) in childhood diseases (e.g., sudden infant death syndrome) in which hypoxia plays a role.
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PMID:Chronic hypoxia in development selectively alters the activities of key enzymes of glucose oxidative metabolism in brain regions. 1271 48

Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)-olfactory bulb pathway and increases in the adult after brain insults. The influence of neonatal injury on SVZ neural precursors is unknown. We examined the effects of hypoxia-ischemia (HI) on neonatal mouse SVZ cell proliferation and neurogenesis. Postnatal day 10 (P10) mice underwent right carotid artery ligation followed by 10% O2 exposure for 45 min. The SVZ area and hemispheric injury were quantified morphometrically 1-3 weeks later. Bromodeoxyuridine (BrdU) was used to label proliferating cells, and cell phenotypes of the progeny were identified by immunohistochemistry. HI significantly enlarged the ipsilateral SVZ at P18, P24, and P31, and increases in the SVZ area correlated directly with the degree of hemispheric damage. HI also stimulated cell proliferation and neurogenesis in the SVZ and peri-infarct striatum. Some newborn cells expressed a neuronal phenotype at P24, but not at P31, indicating that neurogenesis was short-lived. These results suggest that augmenting SVZ neuroblast recruitment and survival may improve neural repair after neonatal brain injury.
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PMID:Neonatal hypoxic-ischemic injury increases forebrain subventricular zone neurogenesis in the mouse. 1526 71

Olfactory dysfunction could happen following various insults such as ischemic-hypoxic state. Neurons of the main olfactory bulb (MOB) are resistant to ischemic damage. In the present study, we investigated the ischemia-related changes of neurons and glial cells in the glomerular layer (GL) of the gerbil MOB after transient ischemia. The number of NeuN-immunoreactive neurons became to decrease from 10 days after ischemic insult. Fifteen days after ischemic insult, astrocytes and microglia were increased in number. By 60 days after ischemia, NeuN-immunoreactive neurons were significantly decreased by 42% per glomerulus. At this time period, astrocytes and microglia were pronouncedly increased. This result indicates that neuronal loss must be much delayed in the GL following transient ischemia.
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PMID:Very delayed neuronal loss occurs in the glomerular layer of the main olfactory bulb following transient ischemia in gerbils. 1528 33

Hypoxia as well as global and focal ischemia are strong activators of neurogenesis in the adult mammalian central nervous system. Here we show that the hypoxia-inducible vascular endothelial growth factor (VEGF) and its receptor VEGFR-2/Flk-1 are expressed in clonally-derived adult rat neural stem cells in vitro. VEGF stimulated the expansion of neural stem cells whereas blockade of VEGFR-2/Flk-1-kinase activity reduced neural stem cell expansion. VEGF was also infused into the lateral ventricle to study changes in neurogenesis in the ventricle wall, olfactory bulb and hippocampus. Using a low dose (2.4 ng/d) to avoid endothelial proliferation and changes in vascular permeability, VEGF stimulated adult neurogenesis in vivo. After VEGF infusion, we observed reduced apoptosis but unaltered proliferation suggesting a survival promoting effect of VEGF in neural progenitor cells. Strong expression of VEGFR-2/Flk-1 was detected in the ventricle wall adjacent to the choroid plexus, a site of significant VEGF production, which suggests a paracrine function of endogenous VEGF on neural stem cells in vivo. We propose that VEGF acts as a trophic factor for neural stem cells in vitro and for sustained neurogenesis in the adult nervous system. These findings may have implications for the pathogenesis and therapy of neurodegenerative diseases.
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PMID:Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. 1544 78

Cerebral ischemia often results in neuronal loss, leading to the neurological deficits in stroke patients. To obtain the functional recovery after stroke, cell transplantation and enhancement of endogenous neurogenesis may have potential application. Recent evidence has demonstrated that neural stem cells exist in the adult mammalian brain. After cerebral ischemia, newly born neurons were found not only in hippocampal dentate and olfactory bulb but also in hippocampal CA1 and striatum, where neurons were lost after ischemia. Administration of neurotrophic factors or genes encoding them into the lateral venticule could enhance endogenous neurogenesis in experimental ischemia model. Furthermore, we have recently developed non-invasive gene transfer into macrophages infiltrating an infarct to stimulate proliferation of neural stem cells in cerebral infarction. Several strategies including gene therapy and pharmacological approach will be tried in stroke patients in near future. However, it remains unclear whether the number of new-born neurons from endogenous neural stem cells is sufficient for replacement of damaged neurons. Cell transplantation will have the advantage of preparing the large amount of transplanted cells. Human neural stem cells, embryonic stem cells and bone marrow-derived cells will be donor cells in stroke patients. Surprisingly, neuron-like cells derived from human teratoma cell line were already applied in stroke patients. However, ethical aspect will have to be discussed carefully before cells from other individuals are used as donor cells in stroke patients.
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PMID:[Therapeutic application of cell transplantation and increased neurogenesis in cerebral infarction]. 1565 Dec 83


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