Chronic but not acute treatment with caffeine attenuates traumatic brain injury in the mouse cortical impact model

W. Lia, 1, S. Daia, 1, J. Ana, P. Lia, X. Chena, R. Xionga, P. Liua, H. Wanga, Y. Zhaoa, M. Zhua, X. Liua, P. Zhua, J.-F. Chenb, , and Y. Zhoua, ,
aMolecular Biology Center, Research Institute of Surgery and Daping Hospital, 10 Changjiang Zhilu, Third Military Medical University, Chongqing 400042, PR China
bDepartment of Neurology, Boston University School of Medicine, 715 Albany Street, C329, Boston, MA 02118, USA

Abstract
Caffeine, the most consumed psychoactive drug and non-specific adenosine receptor antagonist, has recently been shown to exert a neuroprotective effect against brain injury in animal models of Parkinson’s disease (PD) and stroke. However, the effects of caffeine on traumatic brain injury (TBI) are not known. In this study, we investigated the effects of acute and chronic caffeine treatment on brain injury in a cortical-impact model of TBI in mice. Following TBI, neurological deficits, cerebral edema, as well as inflammatory cell infiltration were all significantly attenuated in mice pretreated chronically (for 3 weeks) with caffeine in drinking water compared with the mice pretreated with saline. Furthermore, we found that chronic caffeine treatment attenuated glutamate release and inflammatory cytokine production, effects that were correlated with an upregulation of brain A1 receptor mRNA. By contrast, acute treatment with caffeine (i.p. injection, 30 min before TBI) was not effective in protecting against TBI-induced brain injury. These results suggest that chronic (but not acute) caffeine treatment attenuates brain injury, possibly by A1 receptor-mediated suppression of glutamate release and inhibition of excessive inflammatory cytokine production. These results highlight the potential benefit of chronic caffeine intake for preventing TBI and provide a rationale for the epidemiological investigation of the potential association between TBI and human caffeine intake.

Abbreviations: A1R, A1 receptor; A2AR, A2A receptor; CSF, cerebrospinal fluid; DAPI, 4′-6-diamidino-2-phenylindole; EAE, experimental allergic encephalitis; HPLC, high-performance liquid chromatography; IL-1, interleukin-1; KM, Kunming; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; TBI, traumatic brain injury; TNF-α, tumor necrosis factor-α; TUNEL, terminal deoxynucleotidyl transferase biotin-dUTP nick end-labeling

Source - Neuroscience

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