Increased phospholipase C activity after experimental brain injury

Wei, Enoch P.; Lamb, Robert G.; Kontos, Hermes A.

doi:10.3171/jns.1982.56.5.0695

Cited by 146 publications

(61 citation statements)

References 10 publications

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“…Based on the available evidence, perhaps one of the most likely sources of posttraumatic oxygen radical formation is arachidonic acid oxidation by either prostaglandin synthetase or lipoxygenases (Kukreja et al, 1986). Indeed, activation of the arachidonic acid-liberating enzyme phospholipase C in the brains of fluid percussion head-injured cats has been reported (Wei et al, 1982). Activation of brain phospholipase A, has also been documented in rats subjected to severe concussive head injury (Shohami et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Brain Hydroxyl Radical Generation in Acute Experimental Head Injury

Hall¹,

Andrus²,

Yonkers³

1993

Journal of Neurochemistry

232

109

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Abstract:The time course and intensity of brain hydroxyl radical ('OH) generation were examined in male CF-I mice during the first hour after moderate or severe concussive head injury. Hydroxyl radical production was measured using the salicylate trapping method in which the production of 2.3-and/or 2.5-dihydroxybenzoic acid (DHBA) in brain 15 min after salicylate administration was used as an index of 'OH formation. In mice injured with a concussion of moderate severity asdefined by the I-h posttraumatic neurologic recovery (grip score), a 60% increase in 2,5-DHBA formation was observed by 1 min after injury compared with that observed in uninjured mice. The peak in DHBA formation occurred at 15 min after injury (+67.5%; p < 0.02, compared with uninjured). At 30 min, the increase in DHBA lost significance, indicating that the posttraumatic increase in brain 'OH formation is a transient phenomenon. In severely injured mice, the peak increase in DHBA (both 2,3-and 2,5-) was observed at 30 min after injury, but also fell off thereafter as with the moderate injury severity. Preinjury dosing of the mice with SKF-525A (50 mg/kg i.p.), an inhibitor of microsomal drug oxidations, did not blunt the posttraumatic increase in salicylate-derived 2,5-DHBA, thus showing that it is not due to increased metabolic hydroxylation. Neither injury nor SKF-525A administration affected the DHBA plasma levels. However, saline perfusion of the injured mice to remove the intravascular blood before brain removal eliminated the injury-induced increase in 2,5-DHBA, but did not affect the baseline levels seen in uninjured mice. This implies that the source of the increased DHBA in the injured mice is the microvasculature, probably the endothelium. The administration of the 2 1 -aminosteroid lipid antioxidant, tirilazad mesylate, which possesses 'OH scavenging properties, also attenuated the posttraumatic increase in DHBA, further supporting that it reflects an increase in 'OH radical formation. These results are the first direct demonstration of the occurrence and time course of increased 'OH production in injured brain. Key Words: Hydroxyl radical-Concussion-Salicylate trapping-Brain. Hall E. D. et al. Brain hydroxyl radical generation in acute experimental head injury. J. Neurochem. 60, 588-594 (1 993).

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Section: Discussionmentioning

confidence: 99%

Brain Hydroxyl Radical Generation in Acute Experimental Head Injury

Hall¹,

Andrus²,

Yonkers³

1993

Journal of Neurochemistry

232

109

View full text Add to dashboard Cite

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“…Gerbils (48)(49)(50), but the contribution of intrinsic intracellular XO has not been defined previously. While our results suggest that H202 from XO may contribute to acute edematous cerebral edema after ischemia reperfusion injury, a contribution from neutrophils is also possible.…”

Section: Discussionmentioning

confidence: 99%

“…Test tubes were immediately placed in boiling water for 2.5 min and then in ice water. Aminotriazole 49 and 61%, respectively (Table I). After temporary unilateral carotid artery occlusion, gerbils that had developed mild or severe neurologic deficits during ischemia and had been fed tungsten for 4, 5, or 6 wk had progressively decreased brain edema (Fig.…”

Section: Methodsmentioning

confidence: 99%

Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains.

Patt¹,

Harken²,

Burton³

et al. 1988

J. Clin. Invest.

205

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The contribution of toxic 02 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H202 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H202 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H202 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H202 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while > 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H202 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia.

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“…The release of arachidonic acid and its metabolites is due to activation of cPLA 2 (Shohami et al, 1989), as well as the phospholipase C/diacylglycerol-lipase pathway (Wei et al, 1982). The pathological consequences of alterations in phospholipid metabolism in neural trauma and neurodegenerative diseases may include release of glutamate, energy failure, stimulation of PLA 2 and diacylglycerol lipase activities, free radical damage, and alteration of membrane fluidity and permeability.…”

Section: G Head Injurymentioning

confidence: 99%