LY178002 reduces rat brain damage after transient global forebrain ischemia.

Abstract

1 -4 Although a considerable amount of scientific evidence suggests a role for free radicals in the pathology of ischemia, the actual presence of free radicals during ischemia and reperfusion in the brain, unlike in the heart and other organs, has been difficult to demonstrate.Increases in the amounts of free fatty acids 5 after ischemia and during early reperfusion can provide the substrate for lipid peroxidation and for the formation of products of the arachidonic acid cascade. These products, in particular thromboxane and platelet activating factor, are believed to play a deleterious role in ischemic brain. Received September 20, 1990; accepted April 11, 1991. let activating factor at the receptor level reduced the volume of focal cortical infarcts.

Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N -methyl- d -aspartic acid-receptors and phospholipase A 2

“…This hypothesis is supported by reports that COX (15,16) and phospholipase A 2 (PLA 2 ) inhibitors (17) reduce hippocampal damage in global ischemia. We studied the regulation of COX-2 mRNA and protein in the rat brain using a model of transient focal ischemia and a KCl model of SD.…”

Phospholipase A2 activity can protect renal tubules from oxygen deprivation injury.

“…Because the latter can compromise cellular integrity, it is widely hypothesized that phospholipase activation (5), with resultant membrane damage, is a critical determinant of hypoxic/ischemic cell injury, in general, and of ischemic acute renal failure (6, 7). This view is supported by experimental observations showing that relatively nonspecific phospholipase inhibitors may ameliorate in vivo and in vitro ischemic/hypoxic cell injury (8)(9)(10)(11), that addition of phospholipase A2 (PLA2) to isolated renal tubules causes direct cytotoxicity (12), and that exogenous PLA2 can exacerbate selected pathways that themselves lead to tubular cell death (2).In the course of exploring some of the consequences of exogenous PLA2 addition to isolated rat renal proximal tubular segments (PTS), a perplexing observation was made: addition of pancreatic PLA2, rather than causing cell injury, actually conferred a marked cytoprotective effect against hypoxic cell death. Given that PLA2 is viewed as a mediator of acute tubular necrosis, rather than a defense against it, the The publication costs of this article were defrayed in part by page charge payment.…”

“…Because the latter can compromise cellular integrity, it is widely hypothesized that phospholipase activation (5), with resultant membrane damage, is a critical determinant of hypoxic/ischemic cell injury, in general, and of ischemic acute renal failure (6,7). This view is supported by experimental observations showing that relatively nonspecific phospholipase inhibitors may ameliorate in vivo and in vitro ischemic/hypoxic cell injury (8)(9)(10)(11), that addition of phospholipase A2 (PLA2) to isolated renal tubules causes direct cytotoxicity (12), and that exogenous PLA2 can exacerbate selected pathways that themselves lead to tubular cell death (2).…”

A phenothiazine derivative reduces rat brain damage after global or focal ischemia.

“…We conducted the four-vessel occlusion study as previously described 14 using male Wistar rats (Hilltop Laboratories, Scottsdale, Pa.) weighing 250-280 g, according to the method of Pulsinelli and Brierley.' 5 In the present study, however, the rats were subjected to a 10-minute period of four-vessel occlusion.…”