Hypoxia and Cigarette Smoke - A Combined Threat to the Brain: Role of Toll-like Receptor 4 in Neuroinflammatory Changes

The mammalian brain is composed of 20% of oxygen. The depletion in the level of oxygen may lead to hypoxia, resulting in neurological changes. Recent findings of Toll-like receptors (TLR) such as TLR-2, 3, 4 and 8 in the mammalian nervous system showedneuroinflammation in the brain. The activation of TLR4 by both exogenous and endogenous ligands leads to various inflammatory diseases likeatherosclerosis, Crohn’s disease, ulcerative colitis, rheumatoid arthritis and prostate cancer. This study confirms the involvement of NF-κB in TLR4-axis-induced neuroinflammationin the brain. Cigarette Smoke contains many toxic chemicals such as carcinogenic compounds which areinjurious to health, causing death worldwide. The role of TLR4 in activating the Brain during Cigarette Smoke exposure is not yet understood. Hence this study reviewed the use of the cell culture in vitro model as well as in vivo mouse model of TLR4-/- mouse exposed to hypobaric hypoxia to test hypothesis. Methodology: This review explored articles fromthe past 15 years to study the action of toll-like receptor 4 in neuroinflammatory changes. Those articles which lacked full texts were excluded from the review. A total of 61 articles were enrolled in this review article. Results: The recent findings of TLR in Neurons, showed the involvement of external stimuli such as Cigarette smoke causing various neurological disorders and brain inflammation. The role of TLR4 in activating the brain during acute and chronic cigarette smoke exposure is not yet investigated and also the neuroimmune mechanisms of cigarette smoke are not yet clearly understood. Conclusion: Smoking-related neurological disorders requirea proper understanding of the mechanisms of such damage for therapeutic development. Hence research should be carried out to study the TLR4 mechanisms and pathways in various inflammatory diseases.