Targeting Microglial Polarization to Improve TBI Outcomes

Title:Targeting Microglial Polarization to Improve TBI Outcomes

Volume: 20 Issue: 3

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 and Shyam Gajavelli*

Affiliation:

• The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miler School of Medicine, Miami, Florida, FL 33136,United States

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

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.

Cite this article as:

Nathalie Matti , Polineni P. Sai, Chin N. Christopher , Fawcett Daniela , Clervius Helene , Maria S.L. Quesada , Legnay Fernandez, Rego Lucas , Mahavadi K. Anil , Jermakowicz J. Walter , SW-T Lee , Yokobori Shoji and Gajavelli Shyam *, Targeting Microglial Polarization to Improve TBI Outcomes, CNS & Neurological Disorders - Drug Targets 2021; 20 (3) . https://dx.doi.org/10.2174/1871527319666200918145903