Postinjury treatment with rolipram increases hemorrhage after traumatic brain injury
Version of Record online: 26 APR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Neuroscience Research
Volume 90, Issue 9, pages 1861–1871, September 2012
How to Cite
Atkins, C.M., Kang, Y., Furones, C., Truettner, J.S., Alonso, O.F. and Dietrich, W.D. (2012), Postinjury treatment with rolipram increases hemorrhage after traumatic brain injury. J. Neurosci. Res., 90: 1861–1871. doi: 10.1002/jnr.23069
- Issue online: 10 JUL 2012
- Version of Record online: 26 APR 2012
- Manuscript Accepted: 22 MAR 2012
- Manuscript Revised: 1 MAR 2012
- Manuscript Received: 22 DEC 2011
- National Institute of Neurological Disorders and Stroke. Grant Numbers: NS056072, NS069721
- blood–brain barrier;
- cerebral blood flow;
The pathology caused by traumatic brain injury (TBI) is exacerbated by the inflammatory response of the injured brain. Two proinflammatory cytokines that contribute to inflammation after TBI are tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). From previous studies using the parasagittal fluid-percussion brain injury model, we reported that the anti-inflammatory drug rolipram, a phosphodiesterase 4 inhibitor, reduced TNF-α and IL-1β levels and improved histopathological outcome when administered 30 min prior to injury. We now report that treatment with (±)-rolipram given 30 min after injury significantly reduced TNF-α levels in the cortex and hippocampus. However, postinjury administration of (±)-rolipram significantly increased cortical contusion volume and increased atrophy of the cortex compared with vehicle-treated animals at 10 days postinjury. Thus, despite the reduction in proinflammatory cytokine levels, histopathological outcome was worsened with post-TBI (±)-rolipram treatment. Further histological analysis of (±)-rolipram-treated TBI animals revealed significant hemorrhage in the contused brain. Given the well-known role of (±)-rolipram of increasing vasodilation, it is likely that (±)-rolipram worsened outcome after fluid-percussion brain injury by causing increased bleeding. © 2012 Wiley Periodicals, Inc.