Early Metabolic and Structural Changes in the Rat Brain Following Trauma in vivo Using MRI

Abstract

Traumatic brain injury (TBI) is characterized by acute physiological changes that may play a significant role in the final outcome for the patient. The understanding of tissue alterations at an early stage following TBI is critical for injury management and prevention of more severe secondary damage. In this study we investigated the early post-traumatic neuro-metabolic changes, and changes in tissue water diffusion using proton magnetic resonance spectroscopy (¹H MRS) and diffusion tensor imaging (DTI) following mild to moderate controlled cortical impact injury on six adult male Sprague-Dawley rats on a 7.0 Tesla animal MRI system. Significant reduction in N-acetylaspartate, glutamate and choline was observed as early as 3 hours following injury. Lactate continued to increase in the ipsilateral hippocampus even at 5 hours indicating increased demands for energy closer to the injury site. Such changes were not observed on the contralateral side at 5 hours. Decreased apparent diffusion coefficient and increased fractional anisotropy was observed among regions in close proximity to impacted regions (ipsilateral hippocampus and bi-lateral thalamus) immediately following TBI, with the ipsilateral hippocampus most affected, followed by ipsilateral thalamus and contralateral thalamus. Remote regions such as the ipsilateral olfactory area were affected to a lesser degree. At the 4 hour time point a large inter-individual variation was observed with an overall trend towards recovery in the ipsilateral hippocampus while the thalamus continued to experience significant changes. Combined information from MRS and DTI suggests a distance effect from the site of injury and the existence of a therapeutic window of about 2-4 hours to limit the cascade of events that may lead to secondary injury.