Subacute and Chronic Cognitive and Cerebrovascular Functional Consequences of Mild Traumatic Brain Injury in Rats

Abstract

Traumatic brain injury (TBI) is the main cause of death and disability in the United States in people younger than 35 years old and is a common cause of wartime injuries. Mild TBI (mTBI) is a predisposing factor for later development of dementia and cerebrovascular disease. Aerobic exercise was reported to improve cognitive function in chronic TBI through improved vascular function. The aims of the study are to characterize and correlate the subacute (10 weeks) and chronic (12 months) cognitive and cerebrovascular functional impairment following mTBI and evaluate the modulating effect of exercise early or late following mTBI on these changes. Sprague-Dawley rats received midline fluid percussion injury or sham procedure and followed for 10 weeks or 12 months with a subgroup of mTBI rats undergoing 5-week treadmill aerobic exercise 2 weeks (early) or 10 months (late) post-injury for 6 weeks. Cognitive function was assessed using novel object recognition (NOR) and novel object location (NOL) tests. Regional cerebral blood volume (CBV) and cerebrovascular reactivity following hypercapneic stimulation (CVR) using contrast magnetic resonance imaging (MRI) and ex vivo pial artery vasoreactivity to intraluminal pressure, angiotensin II and diethylenetriamine NONOate (DETA NONOate) were measured. There was no difference in NOR or NOL at 10 weeks between mTBI and sham. NOR, but not NOL, was reduced in mTBI rats at 12 months. CBV at 10 weeks was higher in the primary somatosensory trunk cortex (trunk) and dentate gyrus regions in mTBI, but not at 12 months. CVR was lower in the trunk region of mTBI rats at 12 months. Compared to sham response at 10 weeks, there was impaired arterial constriction response to 90 mm Hg intraluminal pressure in mTBI rats at 10 weeks and in sham and mTBI rats at 12 months, with no difference seen in response to angiotensin II or DETA-NONOate exposure. There was no correlation between cognitive and vascular outcomes at 10 weeks or 12 months. Early or late exercise did not affect 12-month cognitive or vascular function following mTBI. The study showed chronic impairment in short-term memory cognitive function, regional cerebrovascular reactivity and early onset of impaired cerebrovascular myogenic response in rats subjected to mTBI. The findings of persistent cognitive and cerebrovascular impairment in this animal model enhance our understanding of the long-term consequence of mTBI.