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

The pattern of hippocampal cell death has been studied following hippocampal seizure activity and status epilepticus induced by 110-min stimulation of the perforant pathway in awake rats. The order of vulnerability of principal cells in the different hippocampal subfields--as determined by silver impregnation--was found to be very similar to the pattern found in ischemia; i.e., dentate hilus greater than CA1, subiculum greater than CA3c greater than CA3a,b greater than dentate granule cells. The hilar somatostatin-containing cells were the most vulnerable cell type, whereas all other subpopulations of nonprincipal neurons--visualized by immunocytochemistry for the calcium binding proteins parvalbumin and calbindin--were remarkably resistant. Pyramidal cells in the CA3 region containing neither of the examined calcium binding proteins were more resistant to overexcitation than CA1 pyramidal cells, most of which do contain calbindin. This indicates that no simple relationship exists between vulnerability in status epilepticus and neuronal calcium binding protein content, and that local and/or systemic hypoxia during status epilepticus may be responsible for the ischemic pattern of cell death.
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PMID:Pattern of neuronal death in the rat hippocampus after status epilepticus. Relationship to calcium binding protein content and ischemic vulnerability. 134 49

Calbindin D28k (CaBP) is present throughout the entire cell volume of all dentate granule cells in the rat and its appearance is a useful indicator of their development and maturation. Kindling induces a dramatic reduction of granule cell CaBP content but does not make granule cells any more susceptible to the effects of ischemia in adult rats. Others have reported that the levels of CaBP are regulated by corticosterone but our results (in adrenalectomized Wistar or hypophysectomized Sprague-Dawley rats) suggest that any effect is small and transitory. Parvalbumin (PV) is located quite specifically within the entire cell volume of a subpopulation of GABAergic neurons both in the granule cell layer and hilar zone. It appears quite late in the development of the neurons. Reports that kindling induces an increase in PV immunoreactivity in neurons within the hippocampal formation are not supported by the direct measurement of PV levels by radioimmunoassay. Hypophysectomy resulted in a significant fall in PV levels in a number of brain areas including the combined dentate gyrus/CA3 region of the hippocampal formation.
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PMID:Calcium-binding proteins in the dentate gyrus. 146 67

An antibody against rat calbindin-D28K, a calcium-binding protein present at high concentration in certain neurons of the central and peripheral nervous systems, was used to determine the progression of the pathological events in the rat hippocampus following experimental cerebral ischemia. Calbindin-D28K immunoreactivity is present in dentate granule cells and in the CA1-CA2 pyramidal cells. CA1 subfield contains a higher proportion of calbindin-D28K-positive pyramidal cells than does the CA2 subfield and CA1 cells are more immunoreactive than the CA2 cells. The pyramidal cells of the CA1 and CA2 subfields are vulnerable to ischemia. The cells in the CA1 became necrotic within 3-4 days after ischemia while those of the CA2 became necrotic within 2 days. There was a concomitant decrease in calbindin-D28K immunoreactivity in the whole hippocampal regio superior after ischemia which peaked 3 days postischemia. The difference in CA2 and CA1 vulnerability seemed to be inversely correlated with the calbindin-D28K contents of the CA2 and CA1 pyramidal cells. The decrease in the calbindin-D28K contents of these neurons was accompanied by cell damage. We therefore suggest that calbindin-D28K is an important factor for the survival of pyramidal cells in the hippocampal formation after ischemia.
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PMID:Calbindin-D28K and ischemic damage of pyramidal cells in rat hippocampus. 161 25

Cerebral ischemia can be caused by many diverse conditions such as cardiac arrest and severe hypotension and is often the cause of secondary brain damage following head injury or infantile birth trauma. The inadequate cerebral blood flow can result in permanent loss of essential brain circuitries and neurological deficits. The CA1 region of the hippocampal formation is the region of the brain that is most often lesioned following transient forebrain ischemia and is associated with impairments of learning and memory. Furthermore, the loss of such a large target area can lead to detrimental post-trauma synaptic reorganization. Since methods are not currently available for the prevention of neuronal loss following cerebral ischemia, a number of anatomical methodologies were utilized to investigate whether transplanted neurons had the potential to afford some measure of repair. The hippocampal CA1 region of the rat brain was lesioned by transient forebrain ischemia and subsequently repopulated with suspensions of fetal hippocampal tissue. The ability of the transplanted neurons to remain viable when placed into a degenerating environment was confirmed by the histological demonstration of 3H-thymidine labelled neurons in the lesioned region. Histological and immunohistochemical techniques showed that the transplanted neurons developed cytological features that were indistinguishable from their normal CA1 counterparts, often showed a remarkable degree of organization, and expressed some of the same neuron specific proteins; specifically calbindin-D28K and parvalbumin. Acetylcholinesterase histochemistry and retrograde axonal transport of Fluorogold demonstrated that some afferent and efferent fibre projections to and from the septal nucleus could be reinstated. The data have shown that the transplanted neurons can demonstrate many of the anatomical properties that are characteristic of the adult cells they have replaced and therefore have great potential for the reconstruction of severe focal lesions due to ischemia.
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PMID:Hippocampal neurons transplanted into ischemically lesioned hippocampus: anatomical assessment of survival, maturation and integration. 172 74

The relationship between neuronal calcium binding protein content (calbindin D28K: CaBP and parvalbumin: PV) and vulnerability to ischemia was studied in different regions of the rat brain using the four vessel occlusion model of complete forebrain ischemia. The areas studied, i.e. the hippocampal formation, neocortex, neostriatum and reticular thalamic nucleus (RTN), show a characteristic pattern of CaBP and PV distribution, and are involved in ischemic damage to different degrees. In the hippocampal formation CaBP is present in dentate granule cells and in a subpopulation of the CA1 pyramidal cells, the latter being the most and the former the least vulnerable to ischemia. Non-pyramidal cells containing CaBP in these regions survive ischemia, whereas PV-containing non-pyramidal cells in the CA1 region are occasionally lost. Hilar somatostatin-containing cells and CA3 pyramidal cells contain neither PV nor CaBP. Nevertheless, the latter are resistant to ischemia and the former is the first population of cells that undergoes degeneration. Supragranular pyramidal neurons containing CaBP are the most vulnerable cell group in the sensory neocortex. In the RTN the degenerating neurons contain both PV and CaBP. In the neostriatum, ischemic damage involves both CaBP-positive and negative medium spiny neurons, although the degeneration always starts in the dorsolateral neostriatum containing relatively few CaBP-positive cells. The giant cholinergic interneurons of the striatum contain neither CaBP nor PV, and they are the most resistant cell type in this area. These examples suggest the lack of a consistent and systematic relationship between neuronal CaBP or PV content and ischemic vulnerability. It appears that some populations of cells containing CaBP or PV are more predisposed to ischemic cell death than neurons lacking these proteins. These neurons may express high levels of calcium binding proteins because their normal activity may involve a high rate of calcium uptake and/or intraneuronal release.
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PMID:Relationship of neuronal vulnerability and calcium binding protein immunoreactivity in ischemia. 207 50

The calcium-binding proteins, parvalbumin (PV) and calbindin (CaBP), were used as immunocytochemical markers for two different interneuron populations in the rat hippocampus shortly after transient cerebral ischemia. Besides in interneurons, CaBP immunoreactivity (-i) is located in hippocampal CA1 pyramidal cells and dentate granule cells. Shortly after ischemia, the PV-i and CaBP-i were unchanged but, around the 4th postischemic day, PV-i disappeared from somata and fibers located in CA1, CA3c, and the dentate hilus. Terminal PV-i was unchanged. Within days, the PV-i gradually reappeared, first in somata and then in fibers. The transient loss of PV-i was, on a time scale, closely accompanied by a permanent loss of CaBP-i in CA1 pyramidal cells. CaBP-i in interneurons was unchanged. In order to examine the effect of an increased intracellular calcium concentration on the PV-i and CaBP-i, the calcium ionophore A23187 was stereotaxically injected into CA1. In rats killed 30 min later and processed for PV-i and CaBP-i, both PV-i and CaBP-i had disappeared around the A23187 injection sites. Based on this observation and the changes observed after ischemia, it is suggested that the hippocampal PV-i interneurons suffer from a delayed and reversible calcium accumulation in the days after ischemia. Concomitantly, there could be a decreased synthesis or increased destruction of PV after ischemia.
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PMID:Short-term changes of parvalbumin and calbindin immunoreactivity in the rat hippocampus following cerebral ischemia. 229 4

Histological and immunohistochemical techniques were used to investigate the long-term structural changes that occur in the rat hippocampal formation following the induction of transient forebrain ischemia. Histological analysis showed that after 6-12 months cell loss was still largely restricted to the CA1 region but within this region degeneration was progressive and culminated in a severe shrinkage of the stratum oriens and stratum radiatum. Using the immunohistochemical markers calbindin-D28K and parvalbumin, we were able to demonstrate some of the structural changes that reflect this shrinkage. Calbindin immunohistochemistry clearly illustrated that the shrinkage was primarily due to the loss of the pyramidal neurons and the framework normally provided by their long apical dendrites. Parvalbumin immunostaining demonstrated that although a few GABAergic interneurons survived the insult, their terminal network was reduced greatly and the dendrites which normally extended the length of the stratum radiatum were retracted. Additionally, the normally dense band of parvalbumin immunoreactivity in the stratum lacunosum-moleculare, thought to be indicative of a fiber bundle travelling through the CA1 region, was almost completely depleted. These data illustrate that the primary damage observed in the CA1 region following cerebral ischemia is not static but progressive and may thus have important functional implications.
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PMID:Long-term structural changes in the rat hippocampal formation following cerebral ischemia. 277 6

Repeated episodes of cerebral hypoxia-ischemia can cause primarily striatal neuronal loss in the developing brain. We investigated the effect of repeated episodes of asphyxia on specific neuronal sub-populations of the basal ganglia in late-gestation fetal sheep. Asphyxia was induced in 10 fetal sheep (118-126 days gestation) by occluding the umbilical cord for 5 min. This procedure was repeated four times at 30 min intervals and the brains were fixed 3 days later for histopathology. Immunohistochemical markers were used to identify various populations of neurons in the striatum. Antibodies to calbindin were used to stain the GABAergic medium-sized striatal projection neurons and antibodies to somatostatin and parvalbumin to identify striatal interneurons. Striatal projection neurons to the globus pallidus were recognized by enkephalin immunoreactivity, while the striatonigral terminals were identified in the substantia nigra pars reticulata by substance P immunohistochemical labelling. The results showed a marked loss of calbindin staining in the striatum, evident by both reduced cell numbers and a decrease in neuropil staining. The number of parvalbumin immunoreactive cells was also reduced in the striatum, while somatostatin interneurons were selectively preserved. In addition, immunostaining for enkephalin in the globus pallidus and for substance P in the substantia nigra was markedly reduced. These results show that the stiatal GABAergic medium-sized projection neurons are severely affected by recurrent episodes of asphyxia. These findings are confirmed and extended by the results demonstrating that both the enkephalin/GABA striatopallidal and the substance P/GABA stiatonigral pathways are affected. The results of this study therefore suggest that the efferent striatal projections to the globus pallidus and to the substantia nigra may be involved in asphyxial episodes resulting in cerebral palsy.
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PMID:Repeated asphyxia causes loss of striatal projection neurons in the fetal sheep brain. 760 81

In the normal developing hippocampus of the gerbil, parvalbumin-immunoreactive neurons first appear in the stratum pyramidale of CA3 at postnatal day 15 (P15), and in CA2 and hilus of the dentate gyrus from P21 onwards. Immunoreactive terminals also follow the same sequence from CA3 to CA1 to reach adult patterns by the end of the 1st month. Calbindin D-28k immunoreactivity is seen in the external part of the upper blade of the dentate gyrus at P5, and progresses to the granule cell and molecular layers of the whole gyrus by P15, except for a thin band of immature cells located at the base of the granule cell layer which are calbindin negative. Calbindin immunoreactivity in mossy fibers progresses from the external to the hilar region of CA3 during the same period. A few immunoreactive cells are also found in the stratum radiatum/lacunare of the CA3, but no calbindin-immunoreactive cells are observed in the CA1 and CA2 subfields. The adult pattern of calbindin immunoreactivity is reached at P21. Vulnerability following transient forebrain ischemia for 20 min was examined in the hippocampal formation of gerbils during postnatal development. No cellular damage was seen in animals aged 7 days. Dying cells were observed at the base of the granule cell layer of the dentate gyrus in animals aged 15, 21 and 30 days. Pyramidal cells in the CA3 subfield were also sensitive to ischemia in gerbils aged 15 days, and less frequently in animals aged 21 days. The adult pattern of cellular damage, characterized by selective vulnerability of the CA1 subfield, was seen from day 30 onwards.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Poor correlation between delayed neuronal death induced by transient forebrain ischemia, and immunoreactivity for parvalbumin and calbindin D-28k in developing gerbil hippocampus. 794 74

Changes at the level of gene expression are becoming an increasingly recognized component of the neuronal response to injury. We used Northern analysis and three in vivo models of central nervous system (CNS) injury in the rat to determine whether injury alters the expression of certain gene products related to cellular homeostasis. The three models included kainate (KA)-induced seizures, global ischemia, and lateral fluid percussion injury to the cerebral cortex. Animals were sacrificed at various times after injury, and total RNA was isolated from specific brain regions. Northern blots were hybridized with probes for calbindin-D28K, the 78 and 94 kDa glucose-regulated proteins (grp78, grp94), the inducible 72 kDa heat-shock protein (hsp72), and a control probe for the 18S ribosomal subunit. Results showed that mRNA for calbindin-D28K, grp78, and hsp72 increased in the hippocampus following seizures. Peak expression occurred 6-12 h after administration of KA, and returned towards baseline in most cases by 24 h. Changes in all four transcripts were seen in the hippocampus or cortex following global ischemia, although the return to baseline tended to exceed 24 h for the grps. In the trauma model, mRNA for hsp72 was increased in the cortex ipsilateral to the impact 12 h after injury. These results expand the repertoire of known changes in mRNA expression following CNS injury. The increases in hsp72 and grps indicate the occurrence of a generalized stress response. Furthermore, given the evidence that grp78 and grp94 are induced by calcium ionophores in vitro, and the potential role of calbindin-D28K in buffering cytoplasmic calcium, the changes observed in this study may represent a cellular response to perturbed calcium homeostasis that is known to occur in acute CNS injury.
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PMID:Increased expression of mRNA encoding calbindin-D28K, the glucose-regulated proteins, or the 72 kDa heat-shock protein in three models of acute CNS injury. 801 87


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