Neuroprotective Effect of Exogenous Microglia in Global Brain Ischemia

Imai, Fumihiro; Suzuki, Hiromi; Oda, Jumpei; Ninomiya, Takashi; Ono, Ken; Sano, Hirotoshi; Sawada, Makoto

doi:10.1038/sj.jcbfm.9600362

Cited by 189 publications

(131 citation statements)

References 54 publications

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“…Thus, whereas interleukins levels are associated to inflammation, they are also important mediators in neuroprotection of the damaged tissues. Consistent with this idea is the fact that animals with P2X7R deletion show lack of protection against ischemic injury [81], although administration of exogeneous microglia and subsequent neuroprotection to global brain ischemia has also been reported [82].…”

Section: Neuronal P2x7r In Spinal Cord Injurymentioning

confidence: 86%

Physiological and pathological functions of P2X7 receptor in the spinal cord

Cotrina

Nedergaard

2009

Purinergic Signalling

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ATP-mediated signaling has widespread actions in the nervous system from neurotransmission to regulation of proliferation. In addition, ATP is released during injury and associated to immune and inflammatory responses. Still, the potential of therapeutic intervention of purinergic signaling during pathological states is only now beginning to be explored because of the large number of purinergic receptors subtypes involved, the complex and often overlapping pharmacology and because ATP has effects on every major cell type present in the CNS. In this review, we will focus on a subclass of purinergic-ligand-gated ion channels, the P2X7 receptor, its pattern of expression and its function in the spinal cord where it is abundantly expressed. We will discuss the mechanisms for P2X7R actions and the potential that manipulating the P2X7R signaling pathway may have for therapeutic intervention in pathological events, specifically in the spinal cord.

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Section: Neuronal P2x7r In Spinal Cord Injurymentioning

confidence: 86%

Physiological and pathological functions of P2X7 receptor in the spinal cord

Cotrina

Nedergaard

2009

Purinergic Signalling

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“…Conversely, the ablation of the proliferating microglial cells was associated with a signiWcant decrease in IGF-1 levels. The microglial IGF-1 expression has been also recently reported by Ohtaki et al [104].Using a diVerent experimental approach, Imai and colleagues [58] demonstrated that exogenous transplantation of microglial cell into ischemic brain resulted with an increase in the levels of BDNF. Finally, that activated and proliferating glial cells may indeed represent an important source of neutrophins in post-ischemic brain has been recently demonstrated by Tonchev et al [133].…”

Section: Glial Cells and Trophic Factorsmentioning

confidence: 87%

Inflammation, plasticity and real-time imaging after cerebral ischemia

2009

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With an incidence of approximately 350 in 100,000, stroke is the third leading cause of death and a major cause of disability in industrialized countries. At present, although progress has been made in understanding the molecular pathways that lead to ischemic cell death, the current clinical treatments remain poorly eVective. There is mounting evidence that inXammation plays an important role in cerebral ischemia. Experimentally and clinically, brain response to ischemic injury is associated with an acute and prolonged inXammatory process characterized by the activation of resident glial cells, production of inXammatory cytokines as well as leukocyte and monocyte inWltration in the brain, events that may contribute to ischemic brain injury and aVect brain recovery and plasticity. However, whether the post-ischemic inXammatory response is deleterious or beneWcial to brain recovery is presently a matter of debate and controversies. Here, we summarize the current knowledge on the molecular mechanisms underlying post-ischemic neuronal plasticity and the potential role of inXammation in regenerative processes and functional recovery after stroke. Furthermore, because of the dynamic nature of the brain inXammatory response, we highlight the importance of the development of novel experimental approaches such as real-time imaging. Finally, we discuss the novel transgenic reporter mice models that have allowed us to visualize and to analyze the processes such as neuroinXammation and neuronal repair from the ischemic brains of live animals.

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“…This notion is supported by observations that selective depletion of proliferative microglia exacerbate brain injuries 24,37 and, conversely, that injections of exogenous microglia into the brain ameliorate CNS injuries. 38,39 Many authors have concluded that acute inflammation serves several protective functions, 16 whereas chronic inflammation exacerbates injury. 5,6 In keeping with this traditional view of chronic inflammation, the results of our study demonstrate that microglia/macrophages experience a sustained rise in the destructive M1 phenotype within 1 week after TBI.…”

Section: Discussionmentioning

confidence: 99%

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Wang

Zhang

et al. 2013

J Cereb Blood Flow Metab

398

331

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Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation-induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.

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Neuroprotective Effect of Exogenous Microglia in Global Brain Ischemia

Cited by 189 publications

References 54 publications

Physiological and pathological functions of P2X7 receptor in the spinal cord

Physiological and pathological functions of P2X7 receptor in the spinal cord

Inflammation, plasticity and real-time imaging after cerebral ischemia

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

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