Relationship between Flow-Metabolism Uncoupling and Evolving Axonal Injury after Experimental Traumatic Brain Injury

Abstract

Blood flow-metabolism uncoupling is a well-documented phenomenon after traumatic brain injury, but little is known about the direct consequences for white matter. The aim of this study was to quantitatively assess the topographic interrelationship between local cerebral blood flow (LCBF) and glucose metabolism (LCMRglc) after controlled cortical impact injury and to determine the degree of correspondence with the evolving axonal injury. LCMRglc and LCBF measurements were obtained at 3 hours in the same rat from 18F-fluorodeoxyglucose and 14C-iodoantipyrine coregistered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections and in an additional group at 24 hours using beta-amyloid precursor protein (ß-APP) immunohistochemistry. LCBF was significantly reduced over the ipsilateral hemisphere by 48 ± 15% compared with sham-controls, whereas LCMRglc was unaffected, apart from foci of elevated LCMRglc in the contusion margin. Flow-metabolism was uncoupled, indicated by a significant 2-fold elevation in the LCMRglc/LCBF ratio within most ipsilateral structures. There was a significant increase in ß-APP-stained axons from 3 to 24 hours, which was negatively correlated with LCBF and positively correlated with the LCMRglc/LCBF ratio at 3 hours in the cingulum and corpus callosum. Our study indicates a possible dependence of axonal outcome on flow-metabolism in the acute injury stage.