Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotoxic edema is a phenomenon of the ischemically damaged brain. In the present study we tested a histochemical method that detects this phenomenon based on potassium (K+) levels in the brain. In a first series focal cerebral ischemia was induced by arterial occlusion in 23 gerbils (Meriones unguiculatus). After survival times of 30, 60 and 120 min, the animals were killed and brain section histochemically stained for potassium and quantitatively evaluated with a morphometric method. The results were compared with those using physicochemical techniques. A distinct K+ depletion could be demonstrated in the area of the focal ischemia within a survival time of 30 min, the depletion growing thereafter with increasing survival time. In a second series histochemical and chemical methods were used to study the stability of K+ levels in undamaged brains of 15 healthy rats during postmortem intervals of 2.5 and 5 h. Within these intervals K+ levels were clearly depleted, apparently as a result of cerebral spinal fluid (CSF) diffusion. Even if neuronal injury can be demonstrated histochemically after very brief survival times of about 30 min, postmortem storage of the cadavers rendered detection impossible due to electrolyte and water diffusion. In autoptic human cases, therefore, this technique is of no practical utility in detecting cytotoxic brain edema in postmortem tissue.
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PMID:Histochemical characterization of cytotoxic brain edema. Potassium concentrations after cerebral ischemia and during the postmortem interval. 1098 89

Cerebral ischemia causes cell swelling and breakdown of the blood-brain barrier (BBB). Cytotoxic edema results from energy failure, and vasogenic edema occurs when the blood vessels are damaged. Proteases and free radicals are the end result of a molecular injury cascade. Matrix metalloproteinases (MMPs) are a gene family of extracellular matrix-degrading enzymes that disrupt the BBB. Tight junction proteins (TJPs), occludin and claudin-5, which form the endothelial barrier, are vulnerable to attack by MMPs. Basal lamina proteins, such as fibronectin, laminin, and heparan sulfate, are also degraded by MMPs. Reperfusion injury leads to a biphasic opening of the BBB, with the early opening occurring several hours after the onset of reperfusion due to activation of the constitutive enzyme gelatinase A (MMP-2). This initial opening is transient and followed 24 to 48 hours later by more intense damage to the blood vessel, which is associated with the expression and activation of gelatinase B (MMP-9) and stromelysin-1 (MMP-3). Synthetic MMP inhibitors restore the early integrity of the BBB but are ineffective in the later opening. Because these inhibitors block MMPs involved in angiogenesis and neurogenesis, they also slow recovery. The challenge is to identify agents that will protect the BBB, blocking vasogenic edema without interfering with recovery.
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PMID:Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia. 1761 35