A phospholipase C inhibitor ameliorates postischemic neuronal damage in rats.
OBJECTIVE
The hypothesis of calcium-induced neuronal damage has been proposed regarding brain ischemia. Phospholipase C is an enzyme that catalyzes the phosphodiesteratic cleavage of phosphatidylinositol. The cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C yields 1,4,5-inositol triphosphate, which mediates intracellular release of calcium, and 1,2-diacylglycerol, which is an activator of protein kinase C. We examined the effect of phenylmethylsulfonyl fluoride, a phospholipase C inhibitor, on delayed neuronal damage after transient forebrain ischemia in the hippocampal CA1 subfield in rats to assess the role of phospholipase C in postischemic neuronal damage.


METHODS
Twenty-minute forebrain ischemia was induced using the method of Pulsinelli and Brierley. We measured the neuronal density of the hippocampal CA1 subfield 7 days after reperfusion. The effect of phenylmethylsulfonyl fluoride was tested in both pretreatment and posttreatment groups.


RESULTS
In the vehicle treatment group (n = 13), neuronal density was 51 +/- 42/mm (mean +/- SD). The neuronal densities in the 50-mg/kg (n = 12) and 100-mg/kg (n = 14) phenylmethylsulfonyl fluoride pretreatment groups and the 100-mg/kg (n = 10) phenylmethylsulfonyl fluoride posttreatment group were 99 +/- 50, 150 +/- 55, and 143 +/- 63/mm, respectively. These values were significantly higher than that of the vehicle treatment group (p less than 0.05, p less than 0.01, and p less than 0.01, respectively).


CONCLUSIONS
It is suggested that the activation of phospholipase C has an important role in postischemic delayed neuronal damage.
Umemura
A
A
Department of Neurosurgery, Nagoya City University Medical School, Japan.
Mabe
H
H
Nagai
H
H
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D010664:Phenylmethylsulfonyl Fluoride; D010738:Type C Phospholipases