title: Effects of early rolipram treatment on histopathological outcome after controlled cortical impact injury in mice.
abstract: Traumatic brain injury (TBI) pathology includes contusions, cavitation, cell death, all of which can be exacerbated by inflammation. We hypothesized that an anti-inflammatory drug, rolipram, may reduce pathology after TBI, since in several CNS injury models rolipram reduces inflammation and improves cell survival and functional recovery. Adult male C57BL/6 mice received a craniotomy over the right parietotemporal cortex. Vertically directed controlled cortical impact (CCI) injury was delivered. Naïve controls were used for comparison. At 30 min post-surgery, animals were treated with vehicle or rolipram (1 mg/kg), and then once per day for 3 days. On day 3, the brains were systematically sectioned and stained to visualize the resulting pathology using hematoxylin and eosin (H&E) staining and NeuN immunocytochemistry. Total parietotemporal cortical contusion and cavity volume were significantly increased in rolipram-treated as compared to vehicle-treated CCI animals. Contusion areas at specific bregma levels indicated a significant effect of drug across bregma levels. Neuronal cell loss in the dentate hilus and area CA3 of the hippocampus were similar between vehicle and rolipram-treated animals. Although rolipram is well known to reduce pathology and inflammation in several other CNS injury models, the pathology resulting from CCI was worsened with rolipram at this particular dose and administration schedule. These studies suggest that consideration of the unique characteristics of TBI pathology is important in the extrapolation of promising therapeutic interventions from other CNS injury models.
authors.affiliation: The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136-1060, USA. catkins@med.miami.edu
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Atkins
authors.forename: Maria L
authors.initials: ML
authors.lastname: Cepero
authors.forename: Yuan
authors.initials: Y
authors.lastname: Kang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Liebl
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020889:Rolipram / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058988:Phosphodiesterase 4 Inhibitors; D020889:Rolipram