Early Microvascular and Neuronal Consequences of Traumatic Brain Injury: A Light and Electron Microscopic Study in Rats

Abstract

The purpose of this study was to document the early morphologic consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague-Dawley rats. Normothermic rats (37 degrees C) were injured with a fluid percussion pulse (1.7-2.1 atm) administered by an injury cannula positioned parasagittally over the right cerebral cortex (n = 7). At 45 min following TBI, rats were injected with the protein tracer horseradish peroxidase (HRP) and perfusion fixed or immersion fixed 15 min later for light and electron microscopic analysis. Blood-brain barrier (BBB) breakdown to HRP was present overlying the pial surface and superficial cortical layers of the injured hemisphere. A focal area of severe HRP leakage was also present at the gray-white interface of the lateral cortex. Light microscopic examination of this site revealed petechial hemorrhages associated with small venules. Dark shrunken neurons and swollen astrocytes were detected within cortical areas overlying the evolving contusion, CA3 and CA4 hippocampal subsectors, and lateral thalamus. Ultrastructural studies obtained evidence for irreversible neuronal injury and mechanical damage to vessel walls at this early posttraumatic period. In nonperfused traumatized rats, luminal platelet aggregates were also detected at sites of hemorrhage. In this model of TBI, a consistent pattern of microvascular and neuronal abnormalities can be documented in the early posttraumatic period. Pathomechanisms underlying these early changes are discussed in terms of primary and secondary injury processes.