Diffuse traumatic brain injury in mice is associated with a transient mismatch of cerebral blood flow and energy metabolism.

Abstract

Axonal injuries commonly contribute to poor functional outcomes following traumatic brain injury (TBI). To assess cerebral blood flow (CBF) and energy metabolic disturbances in a TBI model of widespread axonal injury, we exposed 105 adult mice to the central (midline) fluid percussion injury (cFPI) diffuse TBI model, or sham injury, and used 9.4 T magnetic resonance (MR) arterial spin labeling (ASL), cortical and hippocampal mitochondrial respiration, and hippocampal MR spectroscopy at 1- and 7-days post-injury (dpi). Widespread, bilateral CBF reductions were observed at day 1 dpi, changes that were normalized by 7 dpi. However, cortical and hippocampal mitochondrial respiration and reactive oxygen species (ROS) production was not significantly altered at 1 and 7 dpi. Moreover, hippocampal volumes, evaluated by MRI, were not altered by cFPI, and by immunohistochemistry only a few apoptotic hippocampal cells were observed. By MRS, evidence of delayed (7 dpi) membrane disruption (phosphocholine and glycerophosphocholine) and glutamate/glutamine increase were observed. While widespread traumatic axonal pathology associated with functional impairments is observed in this TBI model, early CBF alterations were transient and did not translate into significant energy metabolic disturbances. Instead, the delayed hippocampal metabolite changes observed by MRS may contribute to the functional impairment observed in this diffuse TBI model.