CEREBRAL VASCULAR DYSFUNCTION FOLLOWING TRAUMATIC BRAIN INJURY

Abstract

Traumatic brain injury (TBI) affects more than 1.7 million people in the United States annually, having a major impact on public health. Cerebral autoregulation is altered in humans after TBI and in animal models, reflecting a fundamental loss of pressure‐induced cerebral artery constriction (myogenic tone). We hypothesize that TBI leads to abnormal increases in endothelial nitric oxide (NO) synthesis leading to decreased cerebral vascular tone. A fluid percussion model of brain injury was used to produce moderate TBI in adult Sprague‐Dawley rats and animals were studied 24 h after injury. Magnetic resonance imaging (MRI) demonstrated brain damage and edema involving both the ipsilateral and contralateral sides of the cerebral cortex. Cerebral arteries from TBI animals exhibited decreased cytosolic smooth muscle (SM) Ca2+ and reduced myogenic tone in response to stepwise increases in intravascular pressure compared to controls. Inhibition of NO synthase with Nω‐L‐arginine (L‐NNA) restored myogenic tone and SM Ca2+ in arteries from TBI animals. Bioavailability of NO assessed via 4,5‐diaminofluorescein (DAF‐2 DA) was increased in cerebral artery endothelium of TBI animals compared to controls. These results suggest that enhanced nitric oxide‐mediated vasodilation contributes to loss of myogenic tone and cerebrovascular dysfunction following TBI; this information may ultimately lead to novel therapeutic targets that improve clinical outcomes.