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

The striatum is especially vulnerable to hypoxic-ischemic injury, both in adulthood and during development. Striatal injury is likely to play a major role in the chronic abnormalities of motor control which occur as a consequence of developmental hypoxia-ischemia. Previous studies have shown that two striatal neuron phenotypes, cholinergic and NADPH-diaphorase-positive, are resistant to developmental hypoxia-ischemia, but little is otherwise known of patterns of vulnerability among other striatal neurons. In particular, there has been no data available about patterns of vulnerability within the major striatal neuron group, the medium-sized neurons. Since a major anatomical and functional organization of these neurons is in their localization to either the striosome or the matrix compartments, we have examined the effect of developmental hypoxia-ischemia on these compartments using a quantitative morphologic analysis of immunostaining for the calcium-binding protein calbindin-D28k. We have found that there is a predominant loss of the striosome compartment; in the presence of a mean loss of 33% of total striatal area, there was a 49% decrease in striosomal area. There was also a 41% reduction in the number of striosomes, and a small (14%) but significant decrease in the mean area of individual striosomes. The striosome loss was uniform in the rostrocaudal dimension. At a cellular level, the density of calbindin-positive neurons, expressed as number per unit area, was preserved. While there are several possible explanations for the selective loss of the striosome compartment, one hypothesis is that the lower level of calbindin within these neurons makes them more vulnerable to increases in intracellular calcium, which has been postulated to play a role in hypoxic-ischemic injury. The predominant loss of the striosome compartment following hypoxic-ischemic injury may lead to an imbalance with the functionally distinct matrix system. Such an imbalance may contribute to the abnormalities of motor control observed after this form of injury.
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PMID:Relative loss of the striatal striosome compartment, defined by calbindin-D28k immunostaining, following developmental hypoxic-ischemic injury. 824 62

The authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV) and calbindin D28K (CaBP). Hydrocephalus was induced in 16 adult Wistar rats by intracisternal injection of a kaolin solution, which was confirmed microscopically via atlantooccipital dural puncture. Four control rats received the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and CaBP, and Nissl staining were performed at 1, 2, 3, and 4 weeks after the injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP-immunoreactive (IR) interneurons initially lost their stained processes together with a concomitant loss of homogeneous neuropil staining, followed by the reduction of their total number. With progressive ventricular dilation, GAD- and PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity were almost entirely diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated a reduction of their processes and terminals surrounding the pyramidal cells, with secondary reduction of CaBP-IR pyramidal and granular cells. On the other hand, Nissl staining revealed almost no morphological changes induced by ischemia or neuronal degeneration even in the most severe cases of hydrocephalus. Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before there is evidence of morphological injury. The initial injury of cortical and hippocampal interneurons suggests that the functional deafferentation from intrinsic projection fibers may be the initial neuronal event in hydrocephalic brain injury. Although the mechanism of this impairment is still speculative, these findings emphasize the importance of investigating the neuronal pathophysiology in hydrocephalus.
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PMID:Progressive loss of glutamic acid decarboxylase, parvalbumin, and calbindin D28K immunoreactive neurons in the cerebral cortex and hippocampus of adult rat with experimental hydrocephalus. 901 Apr 28

Transient forebrain ischemia is associated with selective neuronal vulnerability and persistent memory deficit. This study compares functional outcome and morphological changes in rats subjected to post-ischemic CA1 or hilus/dentate gyrus region hippocampal fetal transplantation. Ischemia was produced by bilateral common carotid artery occlusion with hypotension. Fetal hippocampal neurons were transplanted into both sides of the CA1 or hilus/dentate gyrus region of the dorsal hippocampus, 1 week post-ischemia. Four weeks post transplantation, the rats underwent behavioral testing for 5 consecutive days using the water maze trial. All animals were perfusion fixed for morphological studies. Transplants in the CA1 region of the dorsal hippocampus were associated with memory and morphological recovery, while grafts placed into the hilus/dentate gyrus region of the dorsal hippocampus were not. Similarly, neurons transplanted in the CA1 region of the dorsal hippocampus were morphologically similar to CA1 pyramidal cell neurons and stained positive with calbindin D(28k). In contrast the grafts transplanted into the hilus/dentate gyrus region of the dorsal hippocampus were morphologically heterogeneous and staining with calbindin D(28k) was not as robust. Post-ischemic transplantation in the CA1 region of the dorsal hippocampus is effective in improving memory and morphological function.
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PMID:Embryonic transplantation and ischemic memory deficit. 912 83

To evaluate the relative ability of those striatal neuron types containing calbindin or parvalbumin to withstand a Ca(2+)-mediated excitotoxic insult, we injected the NMDA receptor-specific excitotoxin quinolinic acid (QA) into the striatum in mature adult rats and 2 months later examined the relative survival of striatal interneurons rich in parvalbumin and striatal projection neurons rich in calbindin. To provide standardization to the survival of striatal neuron types thought to be poor in Ca2+ buffering proteins, the survival was compared to that of somatostatin-neuropeptide Y (SS/NPY)-containing interneurons and enkephalinergic projection neurons, which are devoid of or relatively poorer in such proteins. The various neuron types were identified by immunohistochemical labeling for these type-specific markers and their relative survival was compared at each of a series of increasing distances from the injection center. In brief, we found that parvalbuminergic, calbindinergic, and enkephalinergic neurons all showed a generally comparable gradient of neuronal loss, except just outside the lesion center, where calbindin-rich neurons showed significantly enhanced survival. In contrast, striatal SS/NPY interneurons were more vulnerable to QA than any of these three other types. These observed patterns of survival following intrastriatal QA injection suggest that calbindin and parvalbumin content does not by itself determine the vulnerability of striatal neurons to QA-mediated excitotoxicity in mature adult rats. For example, parvalbuminergic striatal interneurons were not impervious to QA, while cholinergic striatal interneurons are highly resistant and SS/NPY+ striatal interneurons are highly vulnerable. Both cholinergic and SS/NPY+ interneurons are devoid of any known calcium buffering protein. Similarly, calbindin does not prevent striatal projection neuron vulnerability to QA excitotoxicity. Nonetheless, our data do suggest that calbindin may offer striatal neurons some protection against moderate excitotoxic insults, and this may explain the reportedly slightly greater vulnerability of striatal neurons that are poor in calbindin to ischemia and Huntington's disease.
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PMID:Relative resistance of striatal neurons containing calbindin or parvalbumin to quinolinic acid-mediated excitotoxicity compared to other striatal neuron types. 950 Sep 58

Administration of endogenous corticosterone to intact animals induces calbindin-D28k protein in the hippocampal CA1-CA2 subfields. The fact that this effect on calbindin-D28k was shown to be specific for the hippocampus argues for a receptor-mediated effect on gene expression. In addition, chronic pretreatment with corticosterone aggravates ischemia-induced neuronal damage in the CA3-CA4 subfields. This effect is similar to that of preischemic hyperglycemia, which also induces postischemic seizures and aggravates brain damage, since corticosterone raises blood glucose level and enhances tissue lactic acidosis during ischemia. The energetically compromising qualities of corticosterone indicates that it is a key factor in hippocampal vulnerability. We assume that the increase of calbindin-D28k expression in the CA1-CA2 subfields in corticosterone-treated animals is an adaptive response to the exogenous stress. The lack of adaptive response in CA3-CA4 neurons endangers them by impairing the ability of these neurons to counteract the deleterious effects of calcium. This finding, supports: (1) the hypothesis that corticosterone treatment, when paired with an ischemic insult, causes a prolonged elevation of neuronal [Ca2+]i, in an energy dependent manner, probably through the reduction of calcium efflux and (2) that neurons which do contain calbindin-D28k are particularly predisposed to ischemic insults. The CA1-CA2 neurons express high amounts of calbindin-D28k under stress conditions because their activity may involve a high rate of calcium buffering.
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PMID:Synergy between chronic corticosterone treatment and cerebral ischemia in producing damage in noncalbindinergic neurons. 950 Sep 60

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell modulator. In two studies within the hippocampal formation (HF), CGRP-like immunoreactivity (CGRP-LI) was increased in the inner molecular layer of the dentate gyrus after adrenalectomy and in mossy cells after colchicine-induced destruction of granule neurons. Given the increase in CGRP-LI following damage to the granule cell region of the HF, we investigated another trauma model, ischemia, that targeted different areas of the HF, CA1 region, and subiculum to ascertain the regional expression of this peptide after insult. Following ischemia, light microscopic evaluation showed CGRP-LI in basket cell-like neuronal perikarya within the dorsal subiculum and CA1 region of the hippocampus and in varicose fibers within the CA2 region of the hippocampus. Control rats rarely expressed CGRP-LI within neurons in these regions. In ischemic brains, double-labeled immunocytochemistry with antibodies to various neural markers demonstrated co-localization of CGRP-LI primarily within surviving subicular and CA1 cells resembling interneurons containing parvalbumin-LI or calbindin-LI. Electron microscopic analysis of the CA1 region from ischemic brains showed that CGRP-LI was contained in terminals with numerous small synaptic vesicles that formed symmetric synapses with perikarya and large dendrites of pyramidal cells, some of which were degenerating. Collectively, the data from this study and our previous study indicate that damage induces CGRP-LI expression in interneurons and nonprincipal cells in the area of damage, and we hypothesize that CGRP expression in surviving neurons within damage-related regions of the hippocampus is likely to be an important, and possibly a protective, component of the response of the nervous system to injury.
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PMID:Induction of calcitonin gene-related peptide-like immunoreactivity in hippocampal neurons following ischemia: a putative regional modulator of the CNS injury/immune response. 952 88

The present study examined the development of calcium binding protein-containing neurons in a timed series of fetal neocortical transplants. The immunoexpression of parvalbumin and calbindin, which are subpopulations of GABAergic neurons, have been widely studied in normal development and in disease and injury states. Because of their purported resistance to oxidative injury by their ability to buffer Ca++ influx, these neurons have been particularly studied following ischemia. Because it is likely that oxidative stress is associated with the grafting procedure, we sought to determine if these neurons displayed enhanced survival characteristics. Normally, parvalbumin and calbindin represent about 5-10% of cortical neurons. Within 2-4 wk after grafting the expression of both proteins increased markedly in that a relatively larger number of neurons (27% for parvalbumin) were immunopositive. This increase was transitory, however, and by 4 mo and beyond, confocal microscopic data showed a reduction of over 50% of parvalbumin (+) neurons and processes. Calbindin (+) processes showed a qualitative change in that they were smaller with less terminal branching. Electron microscopy confirmed a substantial reduction in parvalbumin synaptic contacts. Interestingly, in older grafts, remaining parvalbumin neurons were those that were strongly NSE (+) suggesting a link between normal metabolism and Ca++ buffering in grafted neurons. It is possible that in early grafts certain neuronal populations transiently upregulated calcium binding proteins as a defensive mechanism against Ca++ influx associated with oxidative stress. Over time, however, following physiological normalization within grafts, the calcium binding protein (+) neurons are diminished, possibly due to lack of appropriate afferent input to the interneuronal pool.
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PMID:Developmental expression of calcium-binding protein-containing neurons in neocortical transplants. 958 94

Cytoplasmic calcium-binding proteins are thought to shield neurons against damage induced by excessive Ca2+ elevations. Yet, in theory, a mobile cellular Ca2+ buffer could just as well promote neuronal injury by facilitating the rapid dispersion of Ca2+ throughout the cytoplasm. In sharp contrast to controls, in mice lacking the gene for calbindin-D28k, synaptic responses of hippocampal CA1 pyramidal neurons which are normally extremely vulnerable to ischemia, recovered significantly faster and more completely after a transient oxygen-glucose deprivation in vitro, and sustained less cellular damage following a 12 min carotid artery occlusion in vivo. Other cellular and synaptic properties such as the altered adaptation of action potential firing, and altered paired-pulse and frequency potentiation at affected synapses in calbindin-D28k-deficient mice were consistent with a missing intraneuronal Ca2+ buffer. Our findings provide direct experimental evidence against a neuroprotective role for calbindin-D28k.
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PMID:Calbindin-D28k fails to protect hippocampal neurons against ischemia in spite of its cytoplasmic calcium buffering properties: evidence from calbindin-D28k knockout mice. 962 36

Neurogenesis in the dentate gyrus of adult rodents is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. To determine whether ischemia affects neurogenesis, newly divided cells in the dentate gyrus were examined after transient global ischemia in adult gerbils. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry demonstrated a 12-fold increase in cell birth in the dentate subgranular zone 1-2 weeks after 10 min bilateral common carotid artery occlusions. Two minutes of ischemia did not significantly increase BrdU incorporation. Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D28k, indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons. Newborn cells with a neuronal phenotype were first seen 26 d after ischemia, survived for at least 7 months, were located only in the granule cell layer, and comprised approximately 60% of BrdU-labeled cells in the granule cell layer 6 weeks after ischemia. The increased neurogenesis was not attributable to entorhinal cortical lesions, because no cell loss was detected in this region. Ischemic preconditioning for 2 min, which protects CA1 neurons against subsequent ischemic damage, did not prevent increased neurogenesis in the granule cell layer after a subsequent severe ischemic challenge. Thus, ischemia-induced dentate neurogenesis is not attributable to CA1 neuronal loss. Enhanced neurogenesis in the dentate gyrus may be a compensatory adaptive response to ischemia-associated injury and could promote functional recovery after ischemic hippocampal injury.
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PMID:Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. 974 47

Severe perinatal asphyxia can lead to injury and dysfunction of the basal ganglia. Post insult administration of insulin-like growth factor-1 is neuroprotective, particularly in the striatum. Insulin-like growth factor-1 is also known to be a neuromodulator of several types of striatal neurons. The striatum comprises various phenotypic neurons with a complex neurochemical anatomy and physiology. In the present study, we examined the specificity of neuronal rescue with insulin-like growth factor-1 on different striatal neurons. Bilateral brain injury was induced in near term fetal sheep by 30 min of reversible carotid artery occlusion. A single dose of 3 microg of insulin-like growth factor-1 was infused over 1 h into the lateral ventricle 90 min following ischemia. The histological and immunohistochemical outcome were examined after 4 days recovery using paraffin tissue preparations. Insulin-like growth factor-1 treatment (n = 11) significantly reduced the percentage of neuronal loss in the striatum compared with the vehicle treated group (n = 10, 28.3+/-5.1% vs 55.5+/-17.3%, P < 0.005). Immunohistochemical studies showed that ischemia resulted in a significant loss of calbindin-28kd, choline acetyltransferase, parvalbumin, glutamate acid decarboxylase, neuronal nitric oxide synthase and neuropeptide Y immunopositive neurons, compared with sham controls. Insulin-like growth factor-1 markedly prevented the loss of calbindin-28kd (n = 7, P < 0.05), choline acetyltransferase (n = 7, P < 0.05), neuropeptide Y (n = 7, P < 0.05), neuronal nitric oxide synthase (n = 8, P < 0.05) and glutamate acid decarboxylase (n = 9, P < 0.05) immunopositive neurons, but failed to protect parvalbumin (n = 6) immunopositive neurons. The present study indicates that the therapeutic effect of insulin-like growth factor-1 in the basal ganglia is selectively associated with cholinergic and some phenotypic GABAergic neurons. These data suggest a potential role for insulin-like growth factor-1 in preventing cerebral palsy due to perinatal asphyxia.
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PMID:Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep. 1067 Apr 51


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