Targeting Microglial Polarization to Improve TBI Outcomes

Author(s): Matti Nathalie, Sai P. Polineni, Christopher N. Chin, Daniela Fawcett, Helene Clervius, Quesada S.L. Maria, Fernandez Legnay, Lucas Rego, Anil K. Mahavadi, Walter J. Jermakowicz, Lee SW-T, Shoji Yokobori, Shyam Gajavelli*

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 20 , Issue 3 , 2021


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Abstract:

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.

Keywords: Traumatic brain injury, inflammation, microglia, pyroptosis, neuroprotection, post-traumatic stress disorder (PTSD).

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Article Details

VOLUME: 20
ISSUE: 3
Year: 2021
Published on: 18 September, 2020
Page: [216 - 227]
Pages: 12
DOI: 10.2174/1871527319666200918145903
Price: $65

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