Microglial and macrophage polarization—new prospects for brain repair.
The traditional view of the adult brain as a static organ has changed in the past three decades, with the emergence of evidence that it remains plastic and has some regenerative capacity after injury. In the injured brain, microglia and macrophages clear cellular debris and orchestrate neuronal restorative processes. However, activation of these cells can also hinder CNS repair and expand tissue damage. Polarization of macrophage populations toward different phenotypes at different stages of injury might account for this dual role. This Perspectives article highlights the specific roles of polarized microglial and macrophage populations in CNS repair after acute injury, and argues that therapeutic approaches targeting cerebral inflammation should shift from broad suppression of microglia and macrophages towards subtle adjustment of the balance between their phenotypes. Breakthroughs in the identification of regulatory molecules that control these phenotypic shifts could ultimately accelerate research towards curing brain disorders.
Centre of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Xiaoming
X
Hu
Centre of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Rehana K
RK
Leak
Centre of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Yejie
Y
Shi
Centre of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Jun
J
Suenaga
State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, 220 Handan Road, Fudan University, Shanghai 200032, China.
Yanqin
Y
Gao
State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, 220 Handan Road, Fudan University, Shanghai 200032, China.
Ping
P
Zheng
Centre of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Jun
J
Chen
D000818:Animals; D001369:Axons / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000502:physiology*; D001930:Brain Injuries; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D010641:Phenotype; D012038:Regeneration / Q000502:physiology*; D013119:Spinal Cord Injuries; D020521:Stroke