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Targeting Microglial Polarization to Improve TBI Outcomes

2020; Bentham Science Publishers; Volume: 20; Issue: 3 Linguagem: Inglês

10.2174/1871527319666200918145903

1996-3181

Nathalie Matti, Sai Polineni, Christopher Chin, Daniela Fawcett, Hélène Clervius, Quesada S.L. Maria, Fernandez Legnay, Lucas Rego, Anil Mahavadi, Walter J. Jermakowicz, Lee SW-T, Shoji Yokobori, Shyam Gajavelli,

S100 Proteins and Annexins

Traumatic Brain Injury (TBI) is still the worldwide leading cause of mortality and morbidity in young adults. Improved safety measures and advances in critical care have increased chances of surviving a TBI, however, numerous secondary mechanisms contribute to the injury in the weeks and months that follow TBI. The past 4 decades of research have addressed many of the metabolic impairments sufficient to mitigate mortality, however, an enduring secondary mechanism, i.e. neuroinflammation, has been intractable to current therapy. Neuroinflammation is particularly difficult to target with pharmacological agents due to lack of specificity, the blood brain barrier, and an incomplete understanding of the protective and pathologic influences of inflammation in TBI. Recent insights into TBI pathophysiology have established microglial activation as a hallmark of all types of TBI. The inflammatory response to injury is necessary and beneficial while the death of activated microglial is not. This review presents new insights on the therapeutic and maladaptive features of the immune response after TBI with an emphasis on microglial polarization, followed by a discussion of potential targets for pharmacologic and non-pharmacologic treatments. In aggregate, this review presents a rationale for guiding TBI inflammation towards neural repair and regeneration rather than secondary injury and degeneration, which we posit could improve outcomes and reduce lifelong disease burden in TBI survivors.