Brain kininogen following experimental brain injury: evidence for a secondary event

Abstract

✓ Previous studies have shown that following experimental brain injury cerebral arterioles dilate and display endothelial lesions and reduced responsiveness to hypocapnia. These abnormalities are caused by cyclooxygenase-dependent free radical generation. There is evidence that the kallikrein-kinin system may in part stimulate the cyclooxygenase-dependent damage since bradykinin is a powerful stimulator of prostaglandin formation and it has recently been shown that a specific kinin receptor blocker decreases the arteriolar abnormalities caused by injury. In order to further examine the hypothesis that the kallikrein-kinin system is important in inducing damage, rat brain tissue was examined for kininogen, the precursor of kinins, at 10 minutes and 1, 3, 6, 15, 24, 48, and 72 hours after injury. A fluid-percussion brain injury device was attached over the right cerebral cortex of rats and a 1.6-atmosphere pressure injury was administered. The kininogen content was determined by a radioimmunoassay procedure in tissues which were free of intravascular blood. After injury, bleeding was confined mainly to the right hemisphere. The kininogen content in the right hemisphere was significantly elevated by one hour after injury, continued to rise until 15 hours after injury, then was significantly decreased by 2 days after injury. In the left hemisphere, kininogen was significantly elevated at 1 hour postinjury, returned toward control levels over the 3- to 6-hour period after injury, then was again elevated at 15 hours after injury. These studies also show that brain water and cerebrovascular permeability were greater at 15 hours postinjury than at earlier time points. The data further support a role for the kallikrein-kinin system in brain injury and, when considered with the results of other studies, suggest that a secondary event is occurring in the 12- to 24-hour period after neural injury. The authors hypothesize that this secondary event is related to endothelial and vascular repair and may be important for the return of normal cerebrovascular function.