title: Postinjury treatment with rolipram increases hemorrhage after traumatic brain injury.
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.
authors.affiliation: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA. catkins@med.miami.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Atkins
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
authors.forename: C
authors.initials: C
authors.lastname: Furones
authors.forename: J S
authors.initials: JS
authors.lastname: Truettner
authors.forename: O F
authors.initials: OF
authors.lastname: Alonso
authors.forename: W D
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020889:Rolipram