TY - JOUR
T1 - Hydroxyl radical production and lipid peroxidation paralles selective post‐ischemic vulnerability in gerbil brain
AU - Hall, Edward D.
AU - Andrus, P. K.
AU - Althaus, J. S.
AU - Von Voigtlander, P. F.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - The salicylate trapping method was used to investigate the changes in hydroxyl radical (·OH) levels in the selectively vulnerable hippocampus compared to the cerebral cortex of gerbils subjected to a 10 min period of near complete forebrain ischemia. Salicylate‐derived 2,5‐dihydroxybenzoic acid (2,5‐DHBA) was measured in sham‐operated animals and at 1, 5, and 15 min of reperfusion. A basal level of 2,5‐DHBA was also seen in non‐ischemic gerbil brain, both in the hippocampus and cortex. The hippocampal basal level was 160% higher than in the cortex (P < .01). Treatment with the cytochrome P450 inhibitor SKF‐525A (50 mg/kg s.c. 30 min before measurement) did not affect this basal level in either hippocampus or cortex, which argues against a contribution of metabolic salicylate hydroxylation as its source. In contrast, pretreatment with the arachidonic acid cyclo‐oxygenase inhibitor ibuprofen (20 mg/kg s.c.) decreased (−68.8%) the level of salicylate hydroxylation in the hippocampus, but not the cortex. In animals subjected to 10 min of forebrain ischemia, a selective increase in 2,5‐DHBA was observed in the hippocampus at 1 min of reprerfusion which subsided by 5 min. No increase in salicylate hydroxylation was apparent in the cortex within the same time frame. The increase in ·OH in the hippocampus at 1 min of reperfusion was accompanied by a significant decrease (−15%; P < .03) in the hippocampal levels of vitamin E. No loss of vitamin E was observed in the cortex at the same time. It is hypothesized that the selective ischemic vulnerability of the hippocampus is mechanistically related to a selective post‐ischemic burst in ·OH in that region. Moreover, this may be based upon an intrinsically higher level of oxidative stress in that region as a by‐product of greater arachidonic acid turnover. © 1993 Wiley‐Liss, Inc.
AB - The salicylate trapping method was used to investigate the changes in hydroxyl radical (·OH) levels in the selectively vulnerable hippocampus compared to the cerebral cortex of gerbils subjected to a 10 min period of near complete forebrain ischemia. Salicylate‐derived 2,5‐dihydroxybenzoic acid (2,5‐DHBA) was measured in sham‐operated animals and at 1, 5, and 15 min of reperfusion. A basal level of 2,5‐DHBA was also seen in non‐ischemic gerbil brain, both in the hippocampus and cortex. The hippocampal basal level was 160% higher than in the cortex (P < .01). Treatment with the cytochrome P450 inhibitor SKF‐525A (50 mg/kg s.c. 30 min before measurement) did not affect this basal level in either hippocampus or cortex, which argues against a contribution of metabolic salicylate hydroxylation as its source. In contrast, pretreatment with the arachidonic acid cyclo‐oxygenase inhibitor ibuprofen (20 mg/kg s.c.) decreased (−68.8%) the level of salicylate hydroxylation in the hippocampus, but not the cortex. In animals subjected to 10 min of forebrain ischemia, a selective increase in 2,5‐DHBA was observed in the hippocampus at 1 min of reprerfusion which subsided by 5 min. No increase in salicylate hydroxylation was apparent in the cortex within the same time frame. The increase in ·OH in the hippocampus at 1 min of reperfusion was accompanied by a significant decrease (−15%; P < .03) in the hippocampal levels of vitamin E. No loss of vitamin E was observed in the cortex at the same time. It is hypothesized that the selective ischemic vulnerability of the hippocampus is mechanistically related to a selective post‐ischemic burst in ·OH in that region. Moreover, this may be based upon an intrinsically higher level of oxidative stress in that region as a by‐product of greater arachidonic acid turnover. © 1993 Wiley‐Liss, Inc.
KW - brain ischemia
KW - gerbil
KW - hydroxyl radical
KW - lipid peroxidation
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U2 - 10.1002/jnr.490340111
DO - 10.1002/jnr.490340111
M3 - Article
C2 - 8380874
AN - SCOPUS:0027505884
SN - 0360-4012
VL - 34
SP - 107
EP - 112
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 1
ER -