A phospholipase C inhibitor ameliorates postischemic neuronal damage in rats.

Abstract

BACKGROUND AND PURPOSE:

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.

• Authors: A Umemura, H Mabe, H Nagai
• Journal: Stroke (Stroke) Vol. 23 Issue 8 Pg. 1163-6 (Aug 1992) ISSN: 0039-2499 [Print] United States
• PMID: 1636192 (Publication Type: Journal Article)

Chemical References

• Phenylmethylsulfonyl Fluoride
• Type C Phospholipases

Topics

• Animals
• Brain Ischemia (metabolism, pathology)
• Hippocampus (pathology)
• Male
• Neurons (drug effects, pathology)
• Phenylmethylsulfonyl Fluoride (pharmacology)
• Rats
• Rats, Inbred Strains
• Type C Phospholipases (antagonists & inhibitors, metabolism)