Open Access Thesis
Date of Award
Traumatic brain injury (TBI) is a global health problem with significant socio-economic costs. Closed head TBIs are one of the major causes of physical disability and cognitive disorder in young adults and a leading cause of death in children.
Alteration in cerebral blood flow due to an impaired autoregulation is one of the most common consequences of TBI. However, studies related to understanding the temporal changes in CBF following TBI in experimental models are limited. The few available studies report acute reduction in CBF following TBI; knowledge related to CBF changes at sub-acute periods extending to 7 days after TBI is still not known. Furthermore, reduction in CBF has been associated with unfavorable neurological outcome and can render the brain vulnerable to secondary damage. However, thus far no effective interventions that can restore or have shown the potential to restore are available. A few available studies have demonstrated that caffeine acts as a neuroprotectant in several neurological disorders acting through diverse mechanisms. It has been postulated that caffeine may offer neuroprotection by restoring or maintaining adequate CBF following TBI. Thus, studying these CBF changes following TBI and its potential modulation by caffeine pre-treatment forms the central theme of this research.
We investigated the CBF changes in male Sprague Dawley rats at 4hrs, 24 hrs, 3 days and 7 days following closed head injury, with and without caffeine (chronic and acute) pretreatment. TBI was induced using the Marmarou impact acceleration device (2 m height, 450 g weight). Rats subjected to TBI showed reduced regional and global CBF at 4hrs and 7 days following TBI. In contrast, rats that underwent chronic caffeine (1.5 g/L) pretreatment for 3 weeks did not show apparent changes in regional and global CBF following TBI, indicating a potential benefit after TBI. Acute caffeine treatment (150 mg/kg, i.p. injection 30 minutes before TBI) showed significant reductions in CBF at 4 hrs post-TBI, further deteriorating the cerebral perfusion.
Furthermore, chronic caffeine pretreated rats demonstrated significantly reduced surface righting duration following TBI, compared to acute caffeine treated rats subjected to TBI and rats subjected to TBI without caffeine treatment. Therefore, chronic caffeine treatment may be beneficial in offering a degree of neuroprotection against TBI. This study was able to support the hypothesis that chronic caffeine can restore or optimize CBF following TBI and this optimization may be related to the ensuring positive outcomes such as reduced surface righting duration. This may form the stepping stone for further studies on beneficial effects of caffeine in TBI.
Bandaru, Sharath Chandra Reddy, "Traumatic Brain Injury Induced Cerebral Blood Flow Changes - A Potential Role For Caffeine" (2012). Wayne State University Theses. 201.