Post-Injury Treatment with Rolipram Increases Hemorrhage After Traumatic Brain Injury

• Published in: Journal of neuroscience research Vol. 90; no. 9; pp. 1861 - 1871
• Main Authors: Atkins, C.M., Kang, Y., Furones, C., Truettner, J.S., Alonso, O.F., Dietrich, W.D.
• Format: Journal Article
• Language: English
• Published: 26-04-2012
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23069

The pathology caused by traumatic brain injury (TBI) is exacerbated by the inflammatory response of the injured brain. Two pro-inflammatory cytokines that contribute to inflammation after TBI are tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In 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, post-injury administration of (±)-rolipram significantly increased cortical contusion volume and increased atrophy of the cortex as compared to vehicle-treated animals at 10 days post-injury. Thus, despite the reduction in pro-inflammatory 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 to increase vasodilation, it is likely that (±)-rolipram worsened outcome after fluid-percussion brain injury by causing increased bleeding.