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)

It has been appreciated for many years that the recovery of brain protein synthesis activity following a transient ischemic insult lags considerably behind the normalization of brain energy metabolism. More recently, selective increases or decreases in the synthesis of specific proteins have been documented to occur during postischemic recirculation, the best characterized of such changes being the induction of proteins characteristic of the "heat shock" or "stress" response. This review will summarize these developments in the study of changes in gene expression following ischemia, with an emphasis on regional differences in the vulnerability of overall translational activity as well in the expression of stress proteins and their mRNAs. The neuronal localization of the 70 kDa heat shock protein, hsp70, after ischemia is contrasted with its largely glial and vascular induction following a hyperthermic stress. The lasting depression of protein synthesis and sustained expression of hsp70 mRNA in vulnerable hippocampal CA1 neurons appear to be mechanistically related and may constitute markers for cellular pathophysiology leading to neuronal cell loss. Elucidating the mechanisms responsible for cell-specific regulation of stress proteins and other gene products may eventually contribute to a more precise understanding of the evolution of brain injury at the molecular level following diverse insults.
 ...
PMID:Protein synthesis and the heart shock/stress response after ischemia. 227 46

The expression of heat shock protein immunoreactivity in rat brain was evaluated in a model of neonatal hypoxia-ischemia. One-week-old rats were subjected to left carotid artery coagulation and exposure to 8% O2/92% N2 for 2 h (moderate injury) or 3.5 h (severe injury). Animals were sacrificed 1, 12 and 24 h after the hypoxic insult. Cells immunoreactive for the 72 kDa heat shock protein (HSP72) were observed in ipsilateral cortex as early as 1 h after the termination of the hypoxia. After 12 h, neurons in the ipsilateral hippocampus and cortex stained intensely for HSP72 immunoreactivity in the moderately injured group. In the severely injured brains, bilateral staining was observed in neurons and vessels of the hippocampus and cortex. Therefore, cells containing HSP72 immunoreactivity may serve as an early marker for neuronal injury from hypoxia-ischemia in the neonatal rat brain and more importantly may illustrate previously unrecognized areas of central nervous system vulnerability.
 ...
PMID:Hypoxia-ischemia induces heat shock protein-like (HSP72) immunoreactivity in neonatal rat brain. 235 Aug 81

Induction of the 70-kDa heat shock protein, hsp70, has been demonstrated in brain following experimental stroke. In the present study, hsp70 was localized in gerbil brain at intervals after transient ischemia using a monoclonal antibody specific for stress-inducible forms of hsp70-related proteins. Induced immunoreactivity was found only in neurons, primarily in hippocampus, striatum, entorhinal cortex and some neocortical regions. Notably hsp70 accumulation was minimal in hippocampal CA1 neurons which die after brief ischemic episodes, but was most pronounced in dentate granule cells and CA3 neurons which are spared. The peak of CA3 immunoreactivity occurred at 48-h recirculation, at the onset of CA1 neuron loss at 2-4 days, demonstrating that hsp70 induction is also a component of this delayed hippocampal pathophysiology rather than a direct response to the metabolic disruption of the initial ischemic episode. These results suggest that hsp70 immunocytochemistry may serve as a marker for neuronal circuitry involved in proposed excitotoxic mechanisms after ischemia and other stresses. Control animals showed immunoreactivity in ependymal cells lining the ventricles, indicating a role for hsp70 in normal functioning of these specialized cells.
 ...
PMID:Localization of 70-kDa stress protein induction in gerbil brain after ischemia. 322 11

Preconditioning of the gerbil brain with a 2-min period of sublethal ischemia protects against neuronal damage following a subsequent 3-min period of ischemia which normally damages CA1 neurons of the hippocampus (ischemic tolerance). In this study, we investigated the role of a small stress protein, heat shock protein-27, in the induction of ischemic tolerance. For this purpose, we used immunohistochemistry with an antibody against heat shock protein-27. Normal hippocampus contained very low levels of heat shock protein-27. The preconditioning ischemia for 2 min caused little changes in the heat shock protein-27 immunostaining in CA1 neurons but an increase in heat shock protein-27 immunostaining in a small number of astrocytes in the CA3 region and in many astrocytes in the dentate hilus. The second ischemia for 3 min caused no specific changes in heat shock protein-27 immunostaining in CA1 neurons both with and without tolerance in early reperfusion periods. After seven days, destruction of CA1 neurons occurred in animals without preconditioning and reactive astrocytes were intensely immunostained for heat shock protein-27. An intense heat shock protein-27 immunostaining was also seen in astrocytes in the dentate hilus after the second ischemia in both groups. Thus, we observed no temporal correlation between the induction of heat shock protein-27 and the manifestation of ischemic tolerance in the CA1 neurons. Most intense heat shock protein-27 immunostaining was observed in reactive astrocytes that accumulated in the damaged CA1 region and dentate hilus.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:An immunohistochemical study of heat shock protein-27 in the hippocampus in a gerbil model of cerebral ischemia and ischemic tolerance. 747 36

The distribution of the nonconstitutive 72 kDa heat shock protein (HSP) in the brains of rats 24 h following graded periods of hyperthermia was studied immunocytochemically. Hyperthermia induced HSP-72 diffusely in cells throughout the cortex, hippocampus and basal ganglia in a dose dependent manner. The cell morphology and location in white matter appeared non-neuronal. Following ischemia, neuronal HSP expression was prominent. These data raise questions regarding prior reports of hyperthermic induction of neuronal HSP expression and the potential pathogenesis of prior hyperthermia in protection against subsequent neuronal injury from ischemia.
 ...
PMID:Hyperthermia induces 72kDa heat shock protein expression in rat brain in non-neuronal cells. 750 12

Induction of the 72-kDa heat shock protein expression is thought to protect neurons against the subsequent effects of ischemia. However, it is not clear whether the induction of 72-kDa heat shock protein expression by an ischemic event improves neuronal survival. To address this question, we outlined the temporal profile of neuronal induction and expression of the 72-kDa heat shock protein in a model of transient focal ischemia in the rat. Fifty two adult Wistar rats were subjected to middle cerebral artery occlusion of 2 h duration. At 0.5, 3, 6, 9, 12, 24, 48, 96 and 168 h after reopening the artery, coronal brain sections were analyzed using both immunohistochemical methods and hematoxylin and eosin staining to determine the topographic and cellular distribution of the 72-kDa heat shock protein, as well as the extent of neuronal damage. Immunoreactivity to the 72-kDa heat shock protein was not detected in neurons that were destined to become necrotic, and were located in the ischemic core of the brain lesions. However, 72-kDa heat shock protein expression was evident in morphologically intact neurons located in the peripheral zone. The earliest neuronal expression of 72-kDa heat shock protein was detected in animals in which the 2 h occlusion of the middle cerebral artery was followed by 6 h recirculation; the intensity of the 72-kDa heat shock protein immunoreactivity peaked at 48 h, and progressively disappeared 7 days after the ischemic reperfusion event.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neuronal survival is associated with 72-kDa heat shock protein expression after transient middle cerebral artery occlusion in the rat. 751 Nov 57

Previous studies in gerbils have shown that cytoskeletal disruption and a loss of the dendritic microtubule-associated protein, MAP2, may occur after short periods of transient global ischemia. tau, a predominantly axonal microtubule-associated protein, has not been examined following ischemia. We compared neuronal damage with alterations in MAP2, tau, and 72-kD heat shock protein (HSP72) immunostaining at various reperfusion times following 20 min of ischemia in the rat four-vessel occlusion model. tau accumulated in neuronal cell bodies throughout the hippocampal formation 30 min to 2 h after the ischemic insult. Perikaryal tau immunostaining was transient in most regions, but persisted in polymorphic hilar neurons. This was accompanied by a loss of immunostaining in the target of many hilar neurons, the inner molecular layer of the dentate gyrus. The same neuronal populations that exhibited increased tau immunostaining of perikarya later displayed an induction of HSP72 immunoreactivity. In contrast, loss of MAP2 immunostaining was not consistently observed before neuronal death and did not correspond to HSP72 induction. The altered tau immunostaining is not the direct result of excitotoxic insult, as intrahippocampal injection of kainic acid did not cause the somal accumulation of tau, but did cause disruption of MAP2 immunostaining. Taken together, the results suggest that the somal accumulation of tau is an early, sensitive, and selective marker of ischemic insult.
 ...
PMID:Alterations in tau immunostaining in the rat hippocampus following transient cerebral ischemia. 751 35

Myocardial infarction is a dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in the replacement of dead myocardium by a fibrous scar. Many biochemical and metabolic changes have been observed early after the onset of ischemia, but the precise cause of the transition to irreversibility has not been elucidated. However, disruption of the plasmalemma of the sarcolemma is an early event, the presence of which indicates that the ischemic myocytes are dead. Not all ischemic myocytes become irreversibly injured simultaneously in experimental infarction in the canine heart; rather, myocytes die in a transmural wavefront of cell death proceeding from the subendocardial to the subepicardial myocardium with the subendocardial layer dying first and the subepicardial layer last. About 6 hours of ischemia are required to complete the wave-front. During the reversible phase of ischemic injury, reperfusion salvages all ischemic myocytes in all layers, but once lethal injury begins to develop, reperfusion salvages reversibly injured myocytes that are located chiefly in the subepicardial and midmyocardial layers and thereby limits the transmural extent of infarction. The gradual evolution of cell death in experimental acute ischemia provides a basis for limitation of infarct size by reperfusion with arterial blood in man. Many functions of myocardium subjected to reversible episodes of ischemia return to the control condition a few seconds or minutes after the onset of reperfusion. Others, such as repletion of the adenine nucleotide pool, require hours to days to repair. Reversibly injured myocardium exhibits reduced contractile efficiency, termed stunning, which is a form of reperfusion injury. Stunning is reversible; it disappears after hours or days of reperfusion. Finally, reversibly injured myocardium develops adaptive changes that protect it against subsequent episodes of ischemia. One such change, termed ischemic preconditioning, persists for 1-2 hours and serves to delay the development of cell death if the tissue is subjected to a new prolonged episode of ischemia. Another, heat shock protein synthesis, does not appear until the tissue has been reperfused for 12-24 hours; it also protects the myocardium against subsequent ischemic injury. The molecular mechanisms underlying stunning, ischemic preconditioning, and heat shock protein synthesis remain to be established.
 ...
PMID:Myocardial ischemia and reperfusion. 760 85

The inducible isoform of the 70-kDa heat shock protein (HSP) family, HSP 72, has been shown to protect cells from protein-damaging stressors and has been associated with myocardial protection. Because exercise is capable of increasing HSP 72 content, we determined whether exercise induction of HSP 72 also provided myocardial protection. Twenty-eight rats (n = 7 per group) were divided into control, heat-shocked (15 min at 42 degrees C), and two exercised groups. Exercise consisted of either one or three bouts (on 3 consecutive days) of treadmill running for 60 min at 30 m/min. Twenty-four hours after heat shock or exercise, hearts were placed on a Langendorff apparatus and subjected to 30 min of global ischemia followed by 30 min of reperfusion. Left ventricular developed pressure (LVDP), maximal rate of contraction and relaxation (+/- dP/dt, respectively), coronary flow, catalase activity, and HSP 72 content were determined. During reperfusion, hearts from heat-shocked animals and animals subjected to three bouts of exercise recovered a greater percentage of preischemic LVDP and +/- dP/dt compared with controls or animals that exercised only once. Compared with hearts from controls, HSP 72 content was significantly elevated in the hearts of heat-shocked animals and in animals subjected to three bouts of exercise, but not in animals that exercised only once. These results suggest that exercise induction of HSP 72 can confer an enhanced postischemic recovery and may explain, at least in part, the myocardial protection associated with exercise.
 ...
PMID:Enhanced postischemic myocardial recovery following exercise induction of HSP 72. 763 64

Induction of the 70 kDa heat shock protein (HSP70) by hypoxia and/or hypoglycemia and the effects of prior heat shock on injury owing to hypoxia and/or hypoglycemia were studied in rat cerebral endothelial cells. Hypoxia and/or hypoglycemia treatment resulted in increased expression of HSP70 only when such treatment was sufficient to cause detectable injury and when the initial treatment was followed by exposure of the cells to 24 h of normoxia and normoglycemia. Heat shock induced 24 h prior to treatment with 48 h of hypoxia slightly reduced endothelial cell damage as measured by fraction of lactate dehydrogenase release (10% decrease in injury). There was a more dramatic effect of prior heat shock on the moderate damage produced by 12 h of combined hypoxia and hypoglycemia (45% decrease), whereas the severe damage produced by 24 h of hypoxia and hypoglycemia was decreased by prior heat shock by only 16%. These results indicate that the hypoxia and hypoglycemia occurring in conjunction with ischemia are more likely to result in heat shock protein expression when there is injury to the tissue. Furthermore, heat shock protects cerebral endothelial cells from hypoxia and hypoglycemia either by slowing the initial development of injury or by delaying the onset of injury.
 ...
PMID:Amelioration of hypoxic and hypoglycemic damage to cerebral endothelial cells. Effects of heat shock pretreatment. 763 16


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