Three Month Follow-Up of Rat Mild Traumatic Brain Injury: A Combined [ 18 F]FDG and [ 11 C]PK11195 Positron Emission Study

Abstract

Mild traumatic brain injury (mTBI) is the most common cause of head trauma. The time course of functional pathology is not well defined, however. The purpose of this study was to evaluate the consequences of mTBI in rats over a period of 3 months by determining the presence of neuroinflammation ([¹¹C]PK11195) and changes in brain metabolism ([¹⁸F]FDG) with positron emission tomography (PET) imaging. Male Sprague-Dawley rats were divided in mTBI (n = 8) and sham (n = 8) groups. In vivo PET imaging and behavioral tests (open field, object recognition, and Y-maze) were performed at different time points after induction of the trauma. Differences between groups in PET images were explored using volume-of-interest and voxel-based analysis. mTBI did not result in death, skull fracture, or suppression of reflexes. Weight gain was reduced (p = 0.003) in the mTBI group compared with the sham-treated group. No statistical differences were found in the behavioral tests at any time point. Volume-of-interest analysis showed neuroinflammation limited to the subacute phase (day 12) involving amygdala, globus pallidus, hypothalamus, pons, septum, striatum, and thalamus (p < 0.03, d > 1.2). Alterations in glucose metabolism were detected over the 3 month period, with increased uptake in the medulla (p < 0.04, d ≥ 1.2), and decreased uptake in the globus pallidus, striatum, and thalamus (p < 0.04, d ≤ 1.2). Similar findings were observed in the voxel-based analysis (p < 0.05 at corrected cluster level). As a consequence of the mTBI, and in the absence of apparent behavioral alterations, relative brain glucose metabolism was found altered in several brain regions, which mostly correspond with those presenting neuroinflammation in the subacute stage.