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

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.
 ...
PMID:Calbindin-D28K and ischemic damage of pyramidal cells in rat hippocampus. 161 25

The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the lateral part of the CA1 region, while PV-ir was not altered in the CA2 and CA3 areas. Pretreatment with the L-type Ca2+ channel blocker nimodipine prevented the ischemia-induced loss of PV-ir in the CA1, suggesting a role for L-type voltage sensitive calcium channels in the mechanism of early neuronal alterations in the hippocampus CA1 region after focal cerebral ischemia.
 ...
PMID:Nimodipine prevents early loss of hippocampal CA1 parvalbumin immunoreactivity after focal cerebral ischemia in the rat. 775 91

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.
 ...
PMID:Relative loss of the striatal striosome compartment, defined by calbindin-D28k immunostaining, following developmental hypoxic-ischemic injury. 824 62

Although specific patterns of cellular vulnerability have been identified in experimental models of cerebral ischemia, there is little data on the occurrence of similar abnormalities in human ischemia. We therefore used a variety of histochemical methods to define changes affecting specific classes of cells in post-mortem specimens from seven patients with hippocampal and neocortical ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed against nonphosphorylated neurofilaments that labels pyramidal projection neurons, was prominently depleted even when conventional Nissl staining revealed only mild pyknosis. In contrast, staining for other markers such as microtubule-associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a calcium-binding protein found in gamma-aminobutyric acid (GABA)-ergic interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic axons and axonal retraction balls in and around acute ischemic lesions. The pattern of differential changes in immunoreactivity was essentially the same in all acute ischemic injuries, including both diffuse lesions in the CA1 field (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition, immunoreactivity for the immediate early gene product c-fos was enhanced in and around the acute ischemic lesions that we studied. In some very acute lesions, immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was increased in lesions more than a few days old. In contrast, the loss of SMI-32 immunoreactivity persisted in chronic lesions. These findings are consistent with those of experimental ischemia in animals and confirm the relevance of these studies for human cerebral ischemia. The pattern of selective changes also resembles that of injuries induced directly by excitatory amino acids, which may play a significant role in the pathogenesis of ischemic damage.
 ...
PMID:Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia. 827 38

HSP-70 was induced in the gerbil following 20 min of forebrain ischemia. The induction, as revealed with immunohistochemistry, is stronger and longer-lasting in CA3 and dentate gyrus than in CA1. Most neurons in this region, except GABAergic interneurons containing the calcium-binding protein parvalbumin, eventually cease to live as a result of delayed cell death. Double-labeling of inducible HSP-70 and parvalbumin has shown that no co-localization occurs in the hippocampus and neocortex of the gerbil in this model of transient forebrain ischemia. These results show that different thresholds of sensitivity and vulnerability exist for different subpopulations of neurons in the ischemic hippocampus, and suggest that HSP-70 protein induction is probably not essential for the survival of particular neuronal subpopulations subjected to transient ischemia.
 ...
PMID:Survival of parvalbumin-immunoreactive neurons in the gerbil hippocampus following transient forebrain ischemia does not depend on HSP-70 protein induction. 854 18

Following transient global ischemia most of the neurons containing somatostatin in the fascia dentata of the dorsal hippocampal formation die, while somatostatinergic neurons in the CA1 region survive. The neurons react to ischemia with a transiently reduced expression of somatostatin mRNA and peptide. We have tested the hypothesis that this selective vulnerability is solely related to those somatostatinergic neurons which do not express the calcium-binding protein parvalbumin. Postischemic changes were studied in rat dorsal hippocampus at 2 and 16 days after 10 min of global cerebral ischemia using a four-vessel occlusion model. We performed a double-staining visualizing the mRNA coding for somatostatin by non-radioactive in situ hybridization and parvalbumin protein by immunocytochemistry. Only 5% of the somatostatinergic cells in the fascia dentata contained parvalbumin. The number of somatostatinergic cells was permanently reduced following ischemia. Among surviving neurons we found cells with and without parvalbumin expression. Thus, expression of parvalbumin is not predictive for survival of somatostatinergic cells in the fascia dentata. In contrast, in CA1, 37% of the somatostatinergic cells contained parvalbumin. These cells were unaffected by the transient ischemic period. The somatostatinergic cells lacking parvalbumin showed transiently reduced mRNA levels at day 2, but recovered to control values at the 16th postischemic day. Thus, expression of the calcium-buffering protein parvalbumin coincides with resistance of somatostatinergic neurons in CA1 to transient effects of ischemia. We conclude that the calcium-buffering capacity of parvalbumin may partially contribute to the protection of somatostatinergic neurons from ischemia in the dorsal hippocampus. However, the survival of somatostatinergic cells without parvalbumin indicates the importance of other factors as well.
 ...
PMID:Co-localization of somatostatin mRNA and parvalbumin in the dorsal rat hippocampus after cerebral ischemia. 858 97

Delayed cell death of projection cells in the CA1 area of the hippocampus is produced in the adult gerbil following 5 minutes (min) of transient forebrain ischemia. Parvalbumin-immunoreactive local-circuit neurons are resistant to the ischemic insult. Brain-Derived Neurotrophic Factor (BDNF) immunoreactivity is localized in all neurons of the CA1 area in control gerbils. However, TrkB immunoreactivity is observed in a minority of BDNF-immunoreactive neurons in the CA1 area. The number of BDNF-immunoreactive cells in CA1 is dramatically reduced in ischemic gerbils as early as 24 h after ischemia, but the number of TrkB-immunoreactive cells in the CA1 area is maintained following ischemia. Moreover, about 90% of BDNF-immunoreactive cells and about 85% of TrkB-immunoreactive cells in ischemic gerbils co-localize the calcium-binding protein parvalbumin. Finally, BDNF and TrkB are coexpressed in about 95% of CA1 neurons surviving the ischemic insult. These results indicate that a subpopulation of CA1 hippocampal neurons coexpressing TrkB, parvalbumin and BDNF is resistant to transient forebrain ischemia in the gerbil. These results also suggest that a subpopulation of CA1 hippocampal neurons in the gerbil hippocampus is endowed with a putative BDNF/TrkB autocrine regulatory loop that may be involved in both cell survival and synaptic remodeling of the damaged gerbil hippocampus following transient forebrain ischemia.
 ...
PMID:BDNF and TrkB co-localize in CA1 neurons resistant to transient forebrain ischemia in the adult gerbil. 921 Aug 75

Calcium is an important mediator of programmed cell death induced by transient cerebral ischemia, and calcium-binding proteins have been implicated in calcium-regulated signal transduction. Apoptosis-linked gene 2 is a calcium-binding protein required for cell death induced by different apoptotic stimuli. By Western blot analysis, we found that apoptosis-linked gene 2 protein was expressed in normal brains, and that expression increased in ischemic brains after 20 or 90 min of transient focal cerebral ischemia. Immunocytochemistry showed increased apoptosis-linked gene 2 protein expression in frontal cortex, a region where neurons underwent ischemic stress but still survived, after 20 or 90 min of focal cerebral ischemia. Apoptosis-linked gene 2 protein was also up-regulated in the ischemic border-zone of parietal cortex 24h after 20 min of focal ischemia, and was remarkably over-expressed in the caudate-putamen and parietal cortex, (where cells are destined to die) 24h after 90 min of ischemia. The expression pattern of apoptosis-linked gene 2 protein was similar to that of deoxyribonucleic acid damage detected by Klenow labeling assay. Our results suggest that apoptosis-linked gene 2 may be involved in the regulation of cell death after transient focal cerebral ischemia.
 ...
PMID:Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia. 1068 20

The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the two carotid arteries combined with arterial hypotension as a method to induce ischemia in rats. We measured the rate of cell production and their state of differentiation with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the immunohistochemical detection of neuronal markers. One week after the ischemic episode, the cell production in dentate gyrus was increased two- to threefold more than the basal level seen in control animals. Two weeks after ischemia, over 60% of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development. Five weeks after the ischemia, over 60% of new neurons expressed calbindin, a calcium-binding protein normally expressed in mature granule neurons. In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia. The maturation rate of neurons as determined by the calbindin labeling and by the rate of migration from a proliferative zone into the granule cell layer was not changed when examined 5 weeks after ischemia. The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain.
 ...
PMID:Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. 1124 73

Mongolian gerbils are epilepsy-prone animals. In adult gerbils two major groups can be differentiated according to their seizure behavior: Highly seizure-sensitive gerbils exhibit facial and forelimb clonus or generalized tonic-clonic seizures from the first test on, while kindled-like gerbils are seizure free for the first three to six consecutive tests, later develop forelimb myoclonus, and eventually progress to generalized tonic-clonic seizures. In the hippocampus, seizure history of the individual animal is mirrored in the intensity in which GABAergic neurons are immunostained for the calcium-binding protein parvalbumin: they lose parvalbumin with increasing seizure incidence. In a first step to clarify the influence of hippocampal projection neurons on spontaneous seizure behavior and related parvalbumin expression, we induced degeneration of the CA1 pyramidal cells by transient forebrain ischemia. This results in a decreased seizure sensitivity in highly seizure-sensitive gerbils. The kindling-like process, however, is not permanently blocked by the ischemic nerve cell loss, suggesting that an intact CA1 field is not a prerequisite for the development of seizure behavior. The seizure-induced loss of parvalbumin from the ischemia-resistant interneurons recovers after ischemia. Thus, changes in parvalbumin content brought about by repeated seizures are not permanent but can rather be modulated by novel stimuli.
 ...
PMID:Ischemia-induced degeneration of CA1 pyramidal cells decreases seizure severity in a subgroup of epileptic gerbils and affects parvalbumin immunoreactivity of CA1 interneurons. 1125 24


1 2 3 Next >>