A pig model with secondary increase of intracranial pressure after severe traumatic brain injury and temporary blood loss.

There is a lack of animal models of traumatic brain injury (TBI) that adequately simulate the longterm changes in intracranial pressure (ICP) increase following clinical TBI. We therefore reproduced the clinical scenario in an animal model of TBI and studied long-term postinjury changes in ICP and indices of brain injury. After induction of anesthesia, juvenile piglets were randomly traumatized using fluid-percussion injury (FPI) to induce either moderate (mTBI = 6 pigs: 3.2 +/- 0.6 atm) or severe (sTBI = 7 pigs: 4.1 +/- 1.0 atm) TBI. Injury was followed by a 30% withdrawal of blood volume. ICP and systemic hemodynamic were monitored continuously. Repeated measurements of global cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were performed at baseline, at the end of blood withdrawal, after volume replacement, and at 8 and 24 h postinjury. Histological and immunocytochemical studies have also performed. ICP peaked immediately following FPI (mTBI: 33 +/- 16 mm Hg; sTBI: 47 +/- 14 mm Hg, p < 0.05) in both groups. In the sTBI group, we noted a second peak at 5 +/- 1.5 h postinjury. This second ICP peak was accompanied by a 50% reduction in CBF (44 +/- 31 mL . min . 100 g(-1)) and CMRO(2) (2.5 +/- 2.0 mL . min . 100 g(1)). Moderate TBI typically resulted in focal pathological change whereas sTBI caused more diffuse change, particularly in terms of the ensuing axonal damage. We thus describe an animal model of severe TBI with a reproducible secondary ICP increase accompanied by patterns of diffuse brain damage. This model may be helpful in the study of pathogenetic relevance of concomitant affections and verify new therapeutic approaches in severe TBI.