We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
PAR-1 deficiency protects against neuronal damage and neurologic deficits after unilateral cerebral hypoxia/ischemia.
- Authors
Olson, Ellen E; Lyuboslavsky, Polina; Traynelis, Stephen F; McKeon, Robert J
- Abstract
Cardiovascular and neurologic surgeries often involve a temporary reduction in cerebral blood flow. In these conditions, as well as during cerebral ischemia and traumatic brain injury, the temporary loss of oxygen and glucose initiates a cascade of cellular events that culminate in neuronal death and damage. Understanding the mechanisms that contribute to neuronal death after hypoxia/ischemia is critically important for treatment of such brain injury. Here, we use a model of combined cerebral hypoxia/ischemia (H/I) to examine the role of protease-activated receptor-1 (PAR-1) in hypoxic/ischemic neuronal damage. Our data show that PAR-1-deficient mice have smaller lesion volumes than wild-type controls after 45 minutes of H/I. The results of the genetic block of PAR-1 were corroborated using a PAR-1 antagonist, which decreased infarct volume in wild-type C57Bl6 mice. Examination of cellular responses to H/I reveals that PAR-1 -/- animals have less cellular death and diminished glial fibrillary acidic protein expression. Additionally, PAR-1 -/- mice exhibit less motor behavior impairment in rotorod and inverted wire-hang tests. These data suggest that PAR-1 contributes to hypoxic/ischemic brain injury and are consistent with other studies that implicate serine proteases and their receptors in neuropathology after cerebral insults.
- Publication
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2004, Vol 24, Issue 9, p964
- ISSN
0271-678X
- Publication type
Journal Article
- DOI
10.1097/01.WCB.0000128266.87474.BF