Neuropathologic characterization of a rodent model of closed head injury -Addition of clinically relevant secondary insults does not significantly potentiate brain damage

We have characterized the early brain pathology in Sprague-Dawley rats subj ected to a modified Richmond impact acceleration model of closed head injur y (CHI). This model was modified to produce maximal traumatic brain injury (TBI) in the absence of skull fracture, extracerebral or intracerebral hemo rrhage, or brain contusion. We then used this model to assess the neuropath ologic effects of superimposed secondary insults, which were designed to re flect a clinically relevant combination of hypotension and pyrexia. Acute n euronal injury, blood-brain barrier (BBB) integrity, axonal injury (AI), an d glial activation were studied 4 1/2 hours following either CHI (group A), CHI plus secondary insults (group B), secondary insults alone (group C), o r sham control injury (group D). There was evidence of limited AI following CHI in the lower medulla and upper cervical cord region, which was not mod ified by addition of secondary insult. Loss of dendritic microtubule-associ ated protein MAP2 immunoreactivity proved a reliable marker of acute neuron al damage, which was confined to subimpact and inferolateral cortical locat ions following CHI and was widespread after secondary insult. The pattern o f plasma protein extravasation paralleled that of acute neuronal injury. We found no evidence of microglial activation, either local or generalized, b y 4 1/2 hours. However, by this time CHI and secondary insults had combined to produce evidence of subimpact astrocyte activation, which was not appar ent with either insult or injury alone. We conclude that in this modified R ichmond model of CHI, when combined with secondary insults, there is no con vincing potentiation of brain damage with the minor exception of astrocyte activation.