Severe Brief Pressure-Controlled Hemorrhagic Shock after Traumatic Brain Injury Exacerbates Functional Deficits and Long-Term Neuropathological Damage in Mice

• DOI: 10.1089/neu.2011.2303
• Publication Date: 2012-06-28T10:30:48Z
• Authors: Joseph N. Hemerka; Xianren Wu; C. Edward Dixon; Robert H. Garman; Jennifer L. Exo; David K. Shellington; Brian Blasiole; Vincent A. Vagni; Keri Janesko-Feldman; Mu Xu; Stephen R. Wisnie...; Hülya Bayır; Larry W. Jenkins; Robert S.B. Clark; Samuel A. Tisherman; Patrick M. Kochanek
• Keywords: Hemorrhagic shock; Brain damage

Hypotension after traumatic brain injury (TBI) worsens outcome. We published the first report of TBI plus hemorrhagic shock (HS) in mice using a volume-controlled approach and noted increased neuronal death. To rigorously control blood pressure during HS, pressure-controlled HS model is required. Our hypothesis was that brief, severe period will exacerbate functional deficits neuropathology versus or alone. C57BL6 male were randomized into four groups (n=10/group): sham, controlled cortical impact (CCI), CCI+HS. used phase (mean arterial [MAP]=25-27 mm Hg for 35 min) its treatment mild to moderate CCI including, 90 min pre-hospital phase, which lactated Ringer's solution given maintain MAP >70 Hg, hospital when shed re-infused. On days 14-20, evaluated Morris water maze (MWM, hidden platform paradigm). day 21, lesion hemispheric volumes quantified. Neuropathology hippocampal neuron counts (hematoxylin eosin [H&E], Fluoro-Jade B, NeuN) (n=60) at 24 h, 7 days, 21 (n=5/group/time point). reduced CCI+HS (p<0.05). Fluid requirements greatest group (p<0.05), sham animals MWM latency on 14 15 Swim speed visible impaired had contusion volume Hemispheric loss 33.3% CA1 cell seen h CA3 (p<0.05 days). only Brief, severe, produces robust exacerbates