Microglia in central nervous system repair after injury

Abstract

Accumulating evidence suggests that immune cells perform crucial inflammation-related functions including clearing dead tissue and promoting wound healing. Thus, they provide a conducive environment for better neuronal regeneration and functional recovery after adult mammalian central nervous system (CNS) injury. However, activated immune cells can also induce secondary damage of intact tissue and inhibit post-injury CNS repair. The inflammation response is due to the microglial production of cytokines and chemokines for the recruitment of peripheral immune cell populations, such as monocytes, neutrophils, dendritic cells and T lymphocytes. Interestingly, microglia and T lymphocytes can be detected at the injured site in both the early and later stages after nerve injury, whereas other peripheral immune cells infiltrate the injured parenchyma of the brain and spinal cord only in the early post-injury phase, and subsequently disappear. This suggests that microglia and T cells may play crucial roles in the post-injury functional recovery of the CNS. In this review, we summarize the current studies on microglia that examined neuronal regeneration and the molecular signalling mechanisms in the injured CNS. Better understanding of the effects of microglia on neural regeneration will aid the development of therapy strategies to enhance CNS functional recovery after injury.

Integrin-Kindlin3 requirements for microglial motility in vivo are distinct from those for macrophages

“…The presence and significance of these structures is documented in several in vivo models focused on microglia, including inflammation and neurogenesis (35,37). Phagosome formation is known to represent a main mechanism for the engulfment of damaged neurons and the processing of cell debris (53). Therefore, the phagosomal defects caused by the lack of Kindlin3-integrin binding might delay the removal of damaged tissue, which, in turn, might later manifest in neurological complications.…”

Regenerative Potential of Ependymal Cells for Spinal Cord Injuries Over Time

“…Besides resident astrocytes and ependymal cells, other glial cell types, including microglia, blood-derived macrophages and stromal cells, also have a major role in glial scar formation after SCI and influence the reactivity of resident astrocytes (Goritz et al, 2011, Jin and Yamashita, 2016, Schwartz, 2010). We investigated whether these mechanisms would also influence the migration and activation of ependymal cells in mild and severe SCI in juvenile and adulthood.…”

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

“…Once provoked, microglia produce pro‐inflammatory cytokines and chemokines, such as IL‐1, IL‐6, IL‐23, interferon gamma‐γ (IFN‐γ), CC chemokine ligand 2 (CCL2) and tumor necrosis factor‐α (TNF‐α) (Natoli et al, ; Nicolas et al, ; Smith, Das, Ray, & Banik, ), which are toxic to neighboring neurons and other glial cells such as astrocytes and oligodendrocytes. Nevertheless, activated microglia are more than simply destructive, it being widely recognized that immunoregulatory microglia are required for regulating brain repair and regeneration by secreting anti‐inflammatory factors, such as IL‐4, IL‐10, IL‐13, and TGF‐β (Cherry, Olschowka, & O'Banion, ; X. Jin & Yamashita, ).…”