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
-
Modulation of Neuro-Inflammation and Vascular Response by Oxidative Stress Following Cerebral Ischemia-Reperfusion Injury
Current Medicinal Chemistry Clinical Applications of Transcranial Doppler Sonography
Reviews on Recent Clinical Trials COVID-19, the Brain, and the Future: Is Infection by the Novel Coronavirus a Harbinger of Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Noninvasive Diagnosis of Chemotherapy Related Cardiotoxicity
Current Cardiology Reviews Endocannabinoid Regulation of Matrix Metalloproteinases: Implications in Ischemic Stroke
Cardiovascular & Hematological Agents in Medicinal Chemistry A Review of Studies on Targeting Interleukin 4 Receptor for Central Nervous System Malignancy
Current Molecular Medicine The Effect of Lipoic Acid on Macro and Trace Metal Levels in Living Tissues Exposed to Oxidative Stress
Anti-Cancer Agents in Medicinal Chemistry Molecular Therapeutic Targets in Inflammation: Cyclooxygenase and NF-κB
Current Drug Targets - Inflammation & Allergy Future Perspectives on the Fibrinolytic Therapy of Intracerebral Hemorrhages
Central Nervous System Agents in Medicinal Chemistry The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia
Current Neurovascular Research Brain Oxidative Stress - Analytical Chemistry and Thermodynamics of Glutathione and NADPH
Current Topics in Medicinal Chemistry A1 Receptors Ligands: Past, Present and Future Trends
Current Topics in Medicinal Chemistry Design and Synthesis of Quinazolinone Derivatives as Anti-inflammatory Agents: Pharmacophore Modeling and 3D QSAR Studies
Medicinal Chemistry Chlorophylls and their Derivatives Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Role of PPAR in Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery The Acid Sphingomyelinase/Ceramide Pathway: Biomedical Significance and Mechanisms of Regulation
Current Molecular Medicine Azelaic Acid: A Promising Agent for Dermatological Applications
Current Drug Therapy Identification of Functional Peptides from Natural and Synthetic Products on Their Anticancer Activities by Tumor Targeting
Current Medicinal Chemistry Transient Receptor Potential Channels - Emerging Novel Drug Targets for the Treatment of Pain
Current Medicinal Chemistry Old Weapons for New Wars: Bioactive Molecules From Cnidarian Internal Defense Systems
Central Nervous System Agents in Medicinal Chemistry