Effects of lipoxygenase inhibitor on cerebral edema induced by freezing lesion in rats.
This study was done to examine the effect of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), on cerebral edema and to substantiate the hypothesis that the metabolites of arachidonic acid are involved in the pathogenesis of cerebral edema. The experiment was performed on rats with vasogenic cerebral edema induced by a freezing lesion. Results demonstrate that the permeability of blood-brain barrier to macromolecules, assessed by Evans blue, was progressively increased and reached a maximum at 24 hrs after freezing untreated rats. At 24 hrs following cold injury, the intracranial pressure was significantly increased from 5.6 +/- 0.4 mmHg to 11.1 +/- 0.8 mmHg and water content from 79.9 +/- 0.3% to 82.7 +/- 0.4%. Sodium and calcium contents increased but potassium decreased significantly as found in untreated cerebral edema tissues. In the nordihydroguaiaretic acid pretreatment group, (3 mg/kg & 6 mg/kg, i.p., 48 hrs in advance) intracranial pressure, water, sodium, and calcium contents were significantly decreased but potassium was increased in cerebral edema tissues. There was no significant difference between untreated controls and immediately post-treated animals. Since NDGA substantially alleviated brain edema, the results suggest that the metabolites of arachidonic acid resulting from the lipoxygenase pathway may contribute to the pathogenesis of cerebral edema.
Yen
M H
MH
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Lee
S H
SH
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism; D004573:Electrolytes / Q000032:analysis; D005615:Freezing; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000493:pharmacokinetics
D004573:Electrolytes; D016859:Lipoxygenase Inhibitors; D012709:Serum Albumin; D009637:Masoprocol