Neuroprotective Effects of Theobromine in Transient Global Cerebral Ischemia-reperfusion Rat Model

Transient global cerebral ischemia (tGCI) is a cerebrovascular disorder characterized by a brief decline in blood flow, neurological deficits, and is often predictive of stroke. Theobromine (TBR) is consumed worldwide in chocolates, tea, and cocoa products. TBR is a natural stimulant and vasoactive alkaloid that may protect against ischemic injury. In this study, neuroprotective potential of theobromine (TBR) was evaluated in 2-vessel occlusion transient global cerebral ischemia-reperfusion (tGCI/R) rat model. Rats were treated with TBR (50, 100 mg/kg, p.o.) for 7 successive days, and subjected to bilateral common carotid artery occlusion (20 min) or sham surgery after last dose of TBR. Severe neurological deficits accompanied by brain infarction, blood-brain barrier abnormalities, and oedema were noted in rats subjected to tGCI/R, and these effects were prevented by TBR. TBR protected against lipid peroxidation and enhanced glutathione level in brain against tGCI/R. TBR pre-treatment for 7 days prevented tGCI/R induced cell death (lactate dehydrogenase, caspase-3), vascular injury (MMP-9), and inflammation (TNF-α, NFκB) in rat whole brain. TBR protected against glutamate excitotoxicity and GABAergic decline in the brain of rats against tGCI/R injury. Findings of this study showed that TBR can alleviate chances of stroke by preventing acute episodes of cerebral ischemia.