Microglia as therapeutic targets after neurological injury: strategy for cell therapy
M Collins Scott1, Supinder S Bedi2, Scott D Olson2
1Department of Pediatric Surgery, University of Texas Health Science Center at Houston (Uthealth), USA.
Introduction:
Microglia is the resident tissue macrophages of the central nervous system. Prolonged microglial activation often occurs after traumatic brain injury and is associated with deteriorating neurocognitive outcomes. Resolution of microglial activation is associated with limited tissue loss and improved neurocognitive outcomes. Limiting the prolonged pro-inflammatory response and the associated secondary tissue injury provides the rationale and scientific premise for considering microglia as a therapeutic target.
Areas Covered:
In this review, we discuss markers of microglial activation, such as immunophenotype and microglial response to injury, including cytokine/chemokine release, free radical formation, morphology, phagocytosis, and metabolic shifts. We compare the origin and role in neuroinflammation of microglia and monocytes/macrophages. We review potential therapeutic targets to shift microglial polarization. Finally, we review the effect of cell therapy on microglia.
Expert Opinion:
Dysregulated microglial activation after neurologic injury, such as traumatic brain injury, can worsen tissue damage and functional outcomes. There are potential targets in microglia to attenuate this activation, such as proteins and molecules that regulate microglia polarization. Cellular therapeutics that limit, but do not eliminate, the inflammatory response have improved outcomes in animal models by reducing pro-inflammatory microglial activation via secondary signaling. These findings have been replicated in early phase clinical trials.
Insights
Targeting microglia, the brain's immune cells, after traumatic brain injury (TBI) may improve neurocognitive outcomes. Modulating microglial activation, rather than eliminating it, shows promise for reducing inflammation and tissue damage.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are central nervous system macrophages implicated in neuroinflammation.
- Prolonged microglial activation post-traumatic brain injury (TBI) correlates with poor neurocognitive function.
- Resolving microglial activation is linked to reduced tissue damage and better outcomes.
Purpose of the Study:
- To review markers and mechanisms of microglial activation.
- To compare microglia with other myeloid cells in neuroinflammation.
- To explore therapeutic targets and cell therapies for modulating microglial responses.
Main Methods:
- Review of literature on microglial activation markers (immunophenotype, cytokine release, morphology, etc.).
- Comparative analysis of microglia and monocyte/macrophage roles in neuroinflammation.
- Examination of therapeutic strategies targeting microglial polarization and cell therapy effects.
Main Results:
- Dysregulated microglial activation exacerbates TBI-induced damage.
- Specific molecular targets exist to modulate microglial polarization.
- Cellular therapeutics show promise in preclinical and early clinical studies for TBI.
Conclusions:
- Microglia represent a viable therapeutic target for neurological injuries like TBI.
- Modulating microglial pro-inflammatory responses is key to improving outcomes.
- Cell-based therapies offer a promising avenue for neuroprotection by regulating microglial activation.
