Superoxide and Nitric Oxide Mechanisms in Traumatic Brain Injury and Hemorrhagic Hypotension.
Abstract
Traumatic brain injury (TBI) renders the brain vulnerable to secondary ischemia and poor outcome after TBI. The goal of this project was to understand the causes of neurological injury due to TBI and hypotension and to use this information to develop treatment strategies to reduce the morbidity of these combined insults. We reported that posttraumatic hypoperfusion can be prevented using L-arginine but that nitric oxide (NO) synthase activity is not affected by TBI, suggesting that TBI is affecting NO directly. We have observed evidence of peroxynitrite (ONOO-) production after TBI and have observed that ONOO- and TBI impair of compensatory cerebral vasodilatory responses. We have performed survival studies after TBI and hemorrhage demonstrating neuronal ischemic injury in 100% of rats subjected to combined injury. Exciting new data suggests that perivascular nerve fibers may modulate myogenic responses through the vasodilatory cannabanoid (CB) receptors. We observed that the destruction of perivascular sensory nerves or CB receptor antagonism reduces myogenic responses to decreased pressure in isolated middle cerebral arteries suggesting that perivascular nerves mediate autoregulation by releasing an agent which dilates the cerebral circulation through CB1 receptors. We observed that hypertonic arginine improves CBF during resuscitation from hypotension after TBI without increasing ICP. These exciting observations cotribute to a better understanding of the mechanisms of traumatic vascular injury and suggest new treatment stategies that will improve functional recovery from TBI and hypotension.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1999
- Accession Number
- ADA373671
Entities
People
- Douglas S. Dewitt
Organizations
- University of Texas Medical Branch