Post-traumatic seizures and changes in brain oxygen contribute to post-traumatic behavioural deficits.

Abstract

Repetitive mild traumatic brain injuries (RmTBIs) are increasingly recognized to have long-term neurological sequelae in a significant proportion of patients. Individuals that have experienced RmTBIs exhibit a variety of physical, cognitive, or behavioural consequences that can negatively impact quality of life. Brain tissue oxygen levels are normally maintained through exquisite regulation of blood supply. However, during neurological events that result in alterations to brain tissue oxygen levels, neuronal dysfunction, brain damage (neuronal loss, astrocyte hypertrophy), and behavioural deficits have been observed, and are frequently related to poorer prognoses. The oxygenation response in the brain after mild TBIs or concussions have been poorly characterized, with most preliminary research limited to the cortex. Furthermore, the mechanisms by which traumatic brain injuries impact changes to brain oxygenation and vice versa remain unclear. In the current study we demonstrate that upon receiving RmTBIs, rats exhibit post-traumatic, electrographic, seizures that are accompanied by a long-lasting period of hippocampal hyperoxygenation. These seizures and the ensuing hyperoxic episodes are associated with deficits in working memory and motor coordination that are reversible through attenuation of the hyperoxia via administration of a calcium channel agonist, Bay K8644. We propose that the post-traumatic, postictal period of altered brain oxygenation is the basis for some of the common symptoms associated with mTBIs.