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)

Much of the work on forebrain ischemia in the hippocampus has focused on the phenomenon of delayed neuronal death in CA1. It is established that dentate granule cells and CA3 pyramidal cells are resistant to ischemia. However, much less is known about interneuronal involvement in CA3 or ischemic injury in the dentate hilus other than the fact that somatostatin neurons in the latter lose their immunoreactivity. We combined two sensitive methods--heat-shock protein (HSP72) immunocytochemistry and a newly developed Gallyas silver stain for demonstrating impaired cytoskeletal elements--to investigate the extent of ischemic damage to CA3 and the dentate hilus using the four-vessel-occlusion model for inducing forebrain ischemia. HSP72-like immunoreactivity was induced in neuronal populations previously shown to be vulnerable to ischemia. In addition, a distinct subset of interneurons in CA3 was also extremely sensitive to ischemia, even more so than the CA1 pyramidal cells. These neurons are located in the stratum lucidum of CA3 and possess a very high density of dendritic spines. In silver preparations, they were among the first to be impregnated as "dark" neurons, before CA1 pyramidal cells; microglial reaction was also initiated first in the stratum lucidum of CA3. Whereas CA1 damage was most prominent in the septal half of the hippocampus, hilar and CA3 interneuronal damage had a more extensive dorsoventral distribution. Our results also show a far greater extent of damage in hilar neurons than previously reported. At least four hilar cell types were consistently compromised: mossy cells, spiny fusiform cells, sparsely spiny fusiform cells, and long-spined multipolar cells. A common denominator of the injured neurons in CA3 and the hilus was the presence of spines on their dendrites, which in large part accounted for the far greater number of mossy fiber terminals they receive than their non-spiny neighbors. We suggest that the differential vulnerability of neuronal subtypes in these two regions may be attributed to their extremely dense innervation by the mossy fibers and/or the presence of non-NMDA receptor subtypes that are highly permeable to calcium. In addition, early impairment of these spiny CA3 cells and hilar neurons after ischemia may be causal to delayed neuronal death in the CA1 pyramidal cells.
 ...
PMID:Vulnerability of mossy fiber targets in the rat hippocampus to forebrain ischemia. 836 55

There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation. 838 Jun 75

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

The purpose of this investigation was to assess the effects of hyperglycemia, in the absence of changes in plasma insulin and arterial free fatty acid (FFA) levels, on interstitial glucose levels and glucose uptake across the left ventricular wall during ischemia in domestic swine. Insulin secretion was suppressed with a continuous infusion of somatostatin. Arterial FFA levels remained stable due to the suppression of insulin. Microdialysis probes were used to estimate changes in interstitial glucose and lactate, and were placed in the subepicardium and the subendocardium of the left anterior descending ([LAD] ischemic) coronary artery perfusion bed and in the midmyocardium of the circumflex ([CFX] nonischemic) perfusion bed. The LAD coronary artery was cannulated and perfused with blood from the femoral artery through an extracorporal perfusion circuit. Ischemia was induced in the LAD perfusion bed by reducing the flow of the LAD perfusion pump by 60% for 50 minutes, and was followed by 30 minutes of reperfusion. Twenty minutes into the ischemic period, seven animals were given a bolus injection of 50% glucose (200 mg/kg) followed by a glucose infusion (10 mg/kg/min), resulting in an increase in arterial glucose levels from 5 to 13 mmol/L in the hyperglycemic group. Hyperglycemia resulted in a marked increase in dialysate glucose during ischemia and a greater than twofold increase in glucose extraction and uptake. Dialysate glucose correlated with plasma glucose in all three perfusion beds. In conclusion, hyperglycemia, in the absence of an increase in insulin and a decrease in arterial FFA, resulted in a doubling of glucose extraction, delivery, and uptake, which corresponded to the twofold elevation in interstitial glucose during ischemia.
 ...
PMID:Hyperglycemia results in an increase in myocardial interstitial glucose and glucose uptake during ischemia. 862 95

To investigate whether differences in vulnerability to free radicals might underlie differences among striatal neurons in their vulnerability to neurodegenerative processes such as occur in ischemia and Huntington's disease, we have analyzed the localization of superoxide free radical scavengers in different striatal neuron types in normal rhesus monkey. Single- and double-label immunohistochemical experiments were carried out using antibodies against the enzymes copper, zinc superoxide dismutase (SOD1), or manganese superoxide dismutase (SOD2), and against markers of various striatal cell types. Our results indicate that the striatal cholinergic and parvalbumin interneurons are enriched in SOD1 and/or SOD2, whereas striatal projection neurons and neuropeptide Y/somatostatin (NPY+/SS+) interneurons express only low levels of both SOD1 and SOD2. We also found that projection neurons of the matrix compartment express significantly higher levels of SOD than those in the striosome compartment. Since projection neurons have been reported to be more vulnerable than interneurons and striosome neurons more vulnerable than matrix neurons to neurodegenerative processes, our results are consistent with the notion that superoxide free radicals are at least partly involved in producing the differential neuron loss observed in the striatum following global brain ischemia or in Huntington's disease.
 ...
PMID:Differential abundance of superoxide dismutase in interneurons versus projection neurons and in matrix versus striosome neurons in monkey striatum. 872 Aug 60

Somatostatin and its stable analogue octreotide are proposed to ameliorate the outcome from acute pancreatitis by inhibiting pancreatic secretion and preventing cell injury. This study investigated the effect of somatostatin analogue octreotide on pancreatic microcirculatory injury (by means of intravital fluorescence microscopy) and enzyme release after ischemia/reperfusion of the pancreas in rats. Octreotide, injected 15 min before the end of 2 h of ischemia as a bolus injection (50 micrograms kg-1 i.v.) or as a continuous infusion (50 micrograms kg-1 h-1 i.v.), attenuated postischemic reperfusion injury of the pancreas as evidenced by a significant (p < 0.05) improvement in capillary perfusion and decrease in leukocyteendothelium interaction in postcapillary venules compared to ischemia without treatment. Pancreas amylase concentration remained unchanged in the octreotide group but increased significantly (p < 0.05) in the ischemia group. These results indicate a protective effect of octreotide against postischemic reperfusion injury of the pancreas in rats.
 ...
PMID:Protective effect of the somatostatin analogue octreotide in ischemia/reperfusion-induced acute pancreatitis in rats. 883 Mar 36

The purpose of the study was to assess myocardial glucose uptake in nondiabetic (n = 5) and streptozotocin-diabetic (n = 6) Yucatan miniature swine under matched hyperglycemic and hypoinsulinemic conditions. Fasting conscious diabetic swine had significantly higher plasma glucose levels (20.9 +/- 2.6 v 5.2 +/- 0.3 mmol/L) and lower insulin levels (6 +/- 1 v 14 +/- 4 microU/mL) than nondiabetic animals. Myocardial glucose uptake was measured in open-chest anesthetized animals under aerobic and ischemic conditions 12 weeks after streptozotocin treatment. Coronary blood flow was controlled by an extracorporeal perfusion circuit. Ischemia was induced by reducing left anterior descending (LAD) coronary artery blood flow by 60% for 40 minutes. Animals were treated with somatostatin to suppress insulin secretion, and nondiabetic swine received intravenous (IV) glucose to match the hyperglycemia in the diabetic animals. The rate of glucose uptake by the myocardium was not statistically different under aerobic conditions, but was significantly lower in diabetic swine during ischemia (0.20 +/- 0.08 v 0.63 +/- 0.14 micromol x g(-1) x min(-1), P < .01). Myocardial glucose transporter (GLUT4) protein concentration was decreased by 31% in diabetic swine. In conclusion, 12 weeks of streptozotocin diabetes in swine caused a significant decrease in myocardial GLUT4 protein and a decrease in myocardial glucose uptake during ischemia.
 ...
PMID:Decreased myocardial glucose uptake during ischemia in diabetic swine. 903 Aug 24

The alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), offers protection to hippocampal CA1 pyramidal cells after short episodes of transient cerebral ischemia. Besides CA1 pyramidal cells, neurons containing somatostatin (SS) and located in the dentate hilus of the hippocampal formation are lost after cerebral ischemia. We studied the protective effects of NBQX on SS neurons in the hilus and on hippocampal CA1 pyramidal cells following 8, 10, or 12 min of four-vessel occlusion ischemia during systemic hypotension. NBQX was administered 3 x 30 mg/kg at 0, 10, and 25 after induction of ischemia or sham, and all rats survived for 7 days. NBQX given to control rats without ischemia had no influence on number or morphology of hilar SS neurons and CA1 pyramidal cells. After 8 min of ischemia, NBQX prevented loss of hilar SS neurons. After 10 and 12 min of ischemia, NBQX had no significant effects on loss of SS neurons in the dentate hilus. However, in all ischemic groups, NBQX significantly reduced loss of CA1 pyramidal cells as compared to control rats. This neuroprotective effect decreased gradually and significantly as the time of ischemia increased. Our results support the observation that SS neurons in hilus are among the most ischemia-vulnerable neurons in the brain. We found that administration of NBQX in generally accepted dosages can protect the rapidly dying SS neurons in hilus from only brief episodes of ischemia.
 ...
PMID:Effects of the AMPA-receptor antagonist, NBQX, on neuron loss in dentate hilus of the hippocampal formation after 8, 10, or 12 min of cerebral ischemia in the rat. 904 Apr 93

Transient cerebral ischemia causes extensive cell death in hippocampal CA1 pyramidal cells and selective loss of interneurons in the dentate hilus. Many hippocampal interneurons can be classified by their contents of somatostatin (SS) and/or neuropeptide Y (NPY). Following ischemia in the rat, most of the NPY immunoreactivity is permanently lost in hippocampus. Furthermore, SS interneurons in the dentate hilus die, whereas CA1 interneurons survive and their expression of SS mRNA and peptide returns to preischemic levels within 16 days after ischemia. We have addressed the following questions: (1) Does the loss of NPY involve a specific downregulation in surviving CA1 interneurons that pre-ischemically expressed both SS and NPY? (2) Can the subpopulation of dying interneurons in hilus be identified from their preischemic coexpression of SS and NPY? We investigated the coexpression of SS mRNA and NPY peptide using combined in situ hybridization and immunocytochemistry. Cells containing one or both markers were counted in control sections and sections taken 2-16 days after ischemia from the hippocampal formation. In CA1, a decrease in the number of neurons containing NPY alone as well as a decrease in the number of neurons coexpressing NPY and SS was observed, whereas the number of neurons containing SS alone increased 16 days after ischemia. We conclude that neurons coexpressing SS and NPY before ischemia added to the number of neurons containing SS alone after ischemia, because NPY expression was selectively down regulated in the coexpressing population. In hilus, we demonstrated both survival and ischemic cell death of neurons expressing either SS, NPY or both, indicating that hilar interneurons dying from ischemia cannot unequivocally be identified from their preischemic colocalization of SS and NPY.
 ...
PMID:Ischemia changes the coexpression of somatostatin and neuropeptide Y in hippocampal interneurons. 926 97

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.
 ...
PMID:Relative resistance of striatal neurons containing calbindin or parvalbumin to quinolinic acid-mediated excitotoxicity compared to other striatal neuron types. 950 Sep 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>