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

Adult neurogenesis is modulated by growth factors, physical conditions, and other alterations in the physical microenvironment. We studied the effects of focal ischemia on neurogenesis in the subventricular zone (SVZ), olfactory bulb (OB), and hippocampal dentate gyrus (DG) (known to be persistent neurogenic regions) in the adult non-human primate, the cynomolgus monkey. Three monkeys underwent middle cerebral artery occlusion-induced focal ischemia and were given multiple BrdU injections during the first 2 weeks after ischemia. Twenty-eight days later, the animals were perfused. The number of new neurons (3182 +/- 408/mm3) in the ipsilateral DG of ischemic monkeys was 4.7-fold that in the DG of non-operated monkeys. The number of new neurons (9176 +/- 2295/mm3) in the ipsilateral olfactory bulb of ischemic monkeys was 18.0-fold that in normal olfactory bulb. These observations suggest an increase in the number of new OB neurons, as well as new DG neurons, after focal ischemia in a primate. This substantial increase in new neurons after focal ischemia could result from the enhancement of cell proliferation rather than a change in the rate of cell commitment. Of the three monkeys subjected to ischemia, only one animal possessed a unique progenitor cell type at the most anterior aspect of the ipsilateral SVZ. Within this region, a short migration (approximately 500 microm) of doublecortin-expressing immature neuronal progenitor cells was observed.
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PMID:Increased number of new neurons in the olfactory bulb and hippocampus of adult non-human primates after focal ischemia. 1671 40

Sensory deficits are frequently observed in cerebral palsy patients. The motor response to smell was found to be abnormal in an animal model of cerebral palsy following fetal hypoxia-ischemia. We hypothesized that fetal hypoxia-ischemia causes long-lasting and selective olfactory tract injury. A population of newborn rabbits with motor deficits was selected after spontaneous delivery following uterine ischemia at 22 days gestation (E22, 70% term). MnCl(2), 20 mg/kg, was administered in both nostrils at postnatal day 1 (E32). One nostril was occluded to control for smell augmentation through the other open nostril by intermittent amyl acetate stimulation for 6 h. T1-weighted MRI images were obtained on newborn rabbits. Amyl acetate exposure increased augmentation of Mn(2+) uptake in olfactory epithelium on the open side in control group but the augmentation was decreased after hypoxia. The proportion of animals with a greater enhancement in the open side increased in controls after amyl acetate, but not in hypoxia. Mn(2+) took longer to arrive at the olfactory bulbs and the rate of subsequent increase was slower in hypoxia. Concomitantly, the thickness of olfactory epithelium and the number of mature olfactory neurons, detected on olfactory marker protein immunostaining, were significantly less in the hypoxic group. Functional MRI studies are superior to neurobehavioral smell testing in the rabbit kits as they are more sensitive and quantifiable measures and do not depend upon the motor response. Antenatal hypoxia-ischemia causes long-lasting injury to neuronal tracts of the olfactory system including olfactory epithelium.
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PMID:Sensory deficits and olfactory system injury detected by novel application of MEMRI in newborn rabbit after antenatal hypoxia-ischemia. 1686 Oct 7

During the last decade, olfactory ensheathing cells (OECs) have been successfully applied in multiple experimental approaches aimed to repair damaged mammalian spinal cord. Some of these experiments have consequently been translated into clinical trials. Finding a reliable source of human OECs that is easily accessible and can ensure a sufficient number of cells is a major prerequisite for conducting studies on OEC-mediated spinal cord regeneration. Here, we present a procedure for obtaining olfactory bulbs (OBs) and olfactory mucosa (OM) simultaneously from adult cadaver heart-beating donors for OEC isolation and analyze some of the factors that may condition successful OEC culture. We show that the results of OEC culture from OBs (10 cases) correlated significantly with warm ischemia time (WIT) as well as the initial viability of the isolated cells. Efficient OEC culture was possible when the WIT for the OB was up to 20 min. Brain damage, assessed by determination of S100B serum level, was not related to the success of OEC culture from the OB. Cadaver OM (7 cases) was shown to be a more reliable source of human OECs than the OB. In most of the examined cases the efficacy of culturing OECs from cadaver OM obtained even 180 min after cardiac arrest was comparable to that of living patients. The method of obtaining OBs and OM from cadavers enables the use of an alternative source of primary adult human OECs for further preclinical and clinical studies on their neurotrophic properties.
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PMID:The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells. 1691 54

The study of the early events that characterize cerebral ischemia is limited in available experimental models. The study of neurophysiological network changes that occur in brain tissue during the early minutes that follow focal ischemia induction is restricted in the in vivo condition. Very simplified systems, such as in vitro brain slices and in isolated neurons, have been utilized for this type of studies. We describe here a new model of transient focal ischemia and reperfusion developed in the isolated guinea pig brain, maintained in vitro by arterial perfusion with a complex saline solution without blood cells. In this preparation, that combines the advantage of an in vitro preparation with the functional preservation of both vascular and neuronal compartments, the arteries of the Willis circle are directly accessible by visual control. To induce transitory focal ischemia, one medial cerebral artery (MCA) was transiently tied for 30 min, while brain activity was recorded with multiple electrodes positioned in brain areas within and outside MCA territory. Anoxic depression in ischemic areas propagated to the surrounding tissue and was associated with the abolition of evoked responses due to both functional impairment of afferent olfactory input and tissue depression. Recovery of evoked responses was obtained after MCA reperfusion. The spatial distribution of hypoxic depressions was characterized and was correlated with the extension of brain damage, defined by immunohistochemical analysis with antibodies against microtubule-associated protein (MAP-2). We propose that the present model can be utilized to analyze brain activity changes that occur in early stages of focal brain ischemia and reperfusion.
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PMID:Early excitability changes in a novel acute model of transient focal ischemia and reperfusion in the in vitro isolated guinea pig brain. 1714 Dec 21

It has been reported that the over-stimulation of N-methyl-D-aspartate receptor (NR) modulates glutamate postsynaptic neurotransmission by generating long lasting Ca2+ channel openings. In the present study, we investigated ischemia-induced change in NR1 immunoreactivity and level in the main olfactory bulb (MOB) after 5 min of transient forebrain ischemia in gerbils. NR1 immunoreactivity in the sham-operated group was shown mainly in tufted cells of the external plexiform and in mitral cells of the mitral cell layer. NR1 immunoreactivity in these neurons was increased with time and was very strong 15 days after ischemia/reperfusion. At that time, NR1 protein level in the MOB was also highest. Thereafter, NR1 immunoreactivity and protein level in the MOB were decreased with time after ischemia/reperfusion. Thus, NR1 in tufted and mitral cells in the gerbil MOB is changed after transient forebrain ischemia. This suggests that mitral and tufted cells may be the principal neurons in the MOB affected in receiving inputs and sending projections to the olfactory area after transient ischemia.
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PMID:N-methyl-D-aspartate receptor type 1 immunoreactivity and protein level in the gerbil main olfactory bulb after transient forebrain ischemia. 1716 May 2

The adult human brain retains the capacity to generate new neurons in the hippocampal formation (Eriksson et al., 1998) and neuronal progenitor cells (NPCs) in the forebrain (Bernier et al., 2000), but to what extent it is capable of reacting to injuries, such as ischemia, is not known. We analyzed postmortem tissue from normal and pathological human brain tissue (n = 54) to study the cellular response to ischemic injury in the forebrain. We observed that cells expressing the NPC marker polysialylated neural adhesion cell molecule (PSA-NCAM) are continuously generated in the adult human subventricular zone (SVZ) and migrate along the olfactory tracts. These cells were not organized in migrating chains as in the adult rodent rostral migratory stream, and their number was lower in the olfactory tracts of brains from old (56-81 years of age) compared with young (29 + 36 years of age) individuals. Moreover, we show that in brains of patients of advanced age (60-87 years of age), ischemia led to an elevated number of Ki-67-positive cells in the ipsilateral SVZ without concomitant apoptotic cell death. Additionally, ischemia led to an increased number of PSA-NCAM-positive NPCs close to the lateral ventricular walls, compared with brains of comparable age without obvious neuropathologic changes. These results suggest that the adult human brain retains a capacity to respond to ischemic injuries and that this capacity is maintained even in old age.
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PMID:Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. 1716

Disorders of the maternal-placental-fetal unit often results in fetal brain injury, which in turn results in one of the highest burdens of disease, because of the lifelong consequences and cost to society. Investigating hypoxia-ischemia in the perinatal period requires the factoring of timing of the insult, determination of end-points, taking into account the innate development, plasticity, and enhanced recovery. Prenatal hypoxia-ischemia is believed to account for a majority of cerebral palsy cases. We have modeled sustained and repetitive hypoxia-ischemia in the pregnant rabbit in utero to mimic the insults of abruptio placenta and labor, respectively. Rabbits have many advantages over other animal species; principally, their motor development is in the perinatal period, akin to humans. Sustained hypoxia-ischemia at 70% (E22) and 79% (E25) caused stillbirths and multiple deficits in the postnatal survivors. The deficits included impairment in multiple tests of spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and the coordination of suck and swallow. Hypertonia was observed in the E22 and E25 survivors and persisted for at least 11 days. Noninvasive imaging using MRI suggests that white matter injury in the internal capsule could explain some of the hypertonia. Further investigation is underway in other vulnerable regions such as the basal ganglia, thalamus and brain stem, and development of other noninvasive determinants of motor deficits. For the first time critical mechanistic pathways can be tested in a clinically relevant animal model of cerebral palsy.
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PMID:A model of cerebral palsy from fetal hypoxia-ischemia. 1726 27

We performed transient global cerebral ischemia on adult macaque monkeys by reversibly stopping blood flow to the brain. We labeled de novo-generated cells in postischemic animals as well as in sham-operated controls by infusing the DNA synthesis indicator BrdU, and subsequently investigated the distribution and phenotype of BrdU-labeled cells in several telencephalic regions at various time-points after ischemia. The ischemic insult significantly increased the number of proliferating cells in the hippocampus, SVZ, neocortex, and striatum, but had no such effect in PHR. In the olfactory bulb, ischemia did not change the proliferating cell levels in the first two postischemic weeks, but did increase these levels at long-term survival time periods. The majority of newly generated cells outside the germinative centers were of a glial phenotype, while neurons constituted only 1% of these cells. Notably, no new neurons were observed in the hippocampal CA1 sector, the region exhibiting the highest vulnerability to ischemia. Within the germinative centers, most BrdU-labeled cells were of a progenitor phenotype and a large proportion of these precursors sustained their existence in the niche for months after ischemia. Furthermore, cells with a progenitor phenotype were identified in brain parenchyma, and these might be responsible for the limited parenchymal neurogenesis as well as for the oligodendrogliogenesis and astrogliogenesis in striatum and neocortex. Our results show that ischemia differentially activates endogenous neural precursors residing in diverse locations of the adult primate CNS. A limited endogenous potential for postischemic neuronal repair exists in neocortex and striatum, but not in the hippocampus proper of the adult macaque monkey brain. The presence of putative parenchymal progenitors and of sustained progenitors in germinative centers opens novel possibilities for precursor cell recruitment to sites of injury. The molecular manipulation of this process may advance our ability to effectively apply brain progenitor cells in the treatment of human neurological diseases.
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PMID:Distribution and phenotype of proliferating cells in the forebrain of adult macaque monkeys after transient global cerebral ischemia. 1740 16

Neural progenitor cells (NPCs) in the subventricular zone (SVZ) travel a long distance along the rostral migratory stream (RMS) to give rise to interneurons in the olfactory bulb (OB). Using the multiphoton microscope and time-lapse recording techniques we here report the behavior of NPCs in the RMS under both intact and ischemic conditions in living brain slices. The NPCs were visualized in 3-week-old transgenic mice that carry the reporter gene, green fluorescent protein (GFP), driven by the nestin promoter. Cortical brain ischemia was induced by permanent occlusion of the right common carotid artery and the middle cerebral artery. We observed that the RMS contained two populations of NPCs: nonmigrating cells (bridge cells) and migrating cells. Bridge cells enabled migrating cells to travel and also produced new cells in the RMS. The direction of NPC migration in the RMS was bidirectional in both intact and ischemic conditions. Cortical ischemia impeded NPC travel in the RMS next to the lesion area during the early period of ischemia. Cell-cell contact was a prominent feature affecting NPC translocation and migratory direction. These data suggest that behavior and function of nestin-positive NPCs in the RMS are variable. Cell-cell contacts and microenvironmental changes influence NPC behavior in the RMS. This study may provide insights to help in understanding NPC biology.
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PMID:Multiphoton microscope imaging: the behavior of neural progenitor cells in the rostral migratory stream. 1772 76

In the present study, we investigated changes in glutamate decarboxylase 65 (GAD65) and GAD67 immunoreactivity and protein levels in the main olfactory bulb (MOB) after 5 min of transient forebrain ischemia in gerbils. GAD65 immunoreactivity in the sham-operated group was shown in neurons and neuropil except for the somata of granule cells. GAD65 immunoreactivity was increased in neurons in the external plexiform layer 60 days after ischemia, and in mitral cells 30 and 60 days after ischemia. GAD67 immunoreactivity in the sham-operated group was shown in periglomerular cells, neuron in the external plexiform layer and granule cells with neuropil. GAD67 immunoreactivity in periglomerular cells was increased 10, 45 and 60 days after ischemia. GAD67 immunoreactivity in neurons in the external plexiform layer was increased 10 and 15 days after ischemia. Mitral cells showed strong GAD67 immunoreactivity 10 days after ischemia. However, GAD67 immunoreactivity in the granule cells was not changed with time after ischemia. In Western blot analysis for GAD65 and GAD67 protein levels in the ischemic gerbil MOB, GAD65 level was not changed after ischemia; GAD67 level was increased 10 days after ischemia. These results suggest that transient ischemia causes changes in GAD65 and GAD67 immunoreactivity in the gerbil MOB, and this change may induce a malfunction in olfaction after an ischemic insult.
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PMID:Comparison of changes in GAD65 and GAD67 immunoreactivity and levels in the gerbil main olfactory bulb induced by transient ischemia. 1794 Aug 93


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