Postinjury treatment with rolipram increases hemorrhage after traumatic brain injury

C. M. Atkins, Y. Kang, C. Furones, J. S. Truettner, O. F. Alonso, W. D. Dietrich

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1861-1871
Number of pages11
JournalJournal of Neuroscience Research
Volume90
Issue number9
DOIs
StatePublished - Sep 1 2012

Keywords

  • Blood-brain barrier
  • CAMP
  • Cerebral blood flow
  • Cytokine
  • Phosphodiesterase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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