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).
CNS & Neurological Disorders - Drug Targets
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1871527319666200918145903 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Magnesium as a Neuroprotective Agent in Cerebral Ischemia
Current Medicinal Chemistry - Central Nervous System Agents Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling
Current Vascular Pharmacology An Overview of Neolignans of the Genus Piper L.: Isolation Methods and Biological Activities
Mini-Reviews in Medicinal Chemistry Diacerein-Thymol Prodrug: <i>In Vivo</i> Release and Pharmacological Screening in Experimental Models of Osteoarthritis in Wistar Rats
Inflammation & Allergy - Drug Targets (Discontinued) Can the Electrophysiological Action of Rosiglitazone Explain its Cardiac Side Effects?
Current Medicinal Chemistry Role of α- and β-adrenergic Mechanisms in the Pathogenesis of Pulmonary Injuries Characterized by Edema, Inflammation and Fibrosis
Cardiovascular & Hematological Disorders-Drug Targets Vascular Endothelial Growth Factor in Central Nervous System Injuries – A Vascular Growth Factor Getting Nervous?
Current Neurovascular Research Pathophysiology of Hypertension During Preeclampsia: Role of Inflammatory Cytokines
Current Hypertension Reviews TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches
CNS & Neurological Disorders - Drug Targets The Molecular Basis of Herpesviruses as Oncolytic Agents
Current Pharmaceutical Biotechnology Remediation of Cellular Hypoxic Damage by Pharmacological Agents
Current Pharmaceutical Design Recent Progress in Therapeutic and Diagnostic Applications of Lanthanides
Mini-Reviews in Medicinal Chemistry Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective
Current Alzheimer Research Colloidal and Pharmacological Activity of Albumin in Clinical Fluid Management:Recent Developments
Current Drug Therapy Hormetic Potential of Sulforaphane (SFN) in Switching Cells’ Fate Towards Survival or Death
Mini-Reviews in Medicinal Chemistry Breakdown of Blood-Brain and Blood-Spinal Cord Barriers During Acute Methamphetamine Intoxication: Role of Brain Temperature
CNS & Neurological Disorders - Drug Targets Synthetic and Natural Coumarins as Cytotoxic Agents
Current Medicinal Chemistry - Anti-Cancer Agents Therapy Against Ischemic Injury
Current Pharmaceutical Design PDE7-Selective and Dual Inhibitors: Advances in Chemical and Biological Research
Current Medicinal Chemistry Bevacizumab and Angiogenesis Inhibitors in the Treatment of CNS Metastases: The Road less Travelled
Current Molecular Pharmacology