Microglia and Their Promising Role in Ischemic Brain Injuries: An Update

Yu, Luting; Su, Xiaojuan; Li, Shiping; Zhao, Fengyan; Mu, Dezhi; Qu, Yi

doi:10.3389/fncel.2020.00211

Cited by 24 publications

(14 citation statements)

References 108 publications

(126 reference statements)

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“…In the sub-acute to chronic stroke phase (e.g. beyond PSD 3), emerging lines of evidence suggest that microglia can proliferate in damaged regions of the cortex and migrate to ischemic core, where they produce a variety of cytokines and engaged in cell debris clean up 28,29 . However, it remains to be elucidated whether the increased IBA-1+ cells in the thalamus that we and others [30][31][32] have shown reflects an increase in the proportion of activated microglia versus an increase in the total number of microglia.…”

Section: Cortical Stroke Induces Neurodegeneration In Ipsilateral Thamentioning

confidence: 99%

Cortical stroke produces secondary injury and long-lasting gliosis in the ipsilateral thalamus

Kim

Stephenson

Mamun

et al. 2020

Preprint

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Remote secondary injury in the thalamus has been observed following cortical infarct, however the mechanisms are not well understood. We used the distal MCAO stroke model (pdMCAO) to explore the cellular and temporal gliosis response in secondary thalamic injury in mice. At 3 days post-stroke (PSD3), primary infarct was limited to the cortex, with no infarct in the thalamus. However, at 2 weeks after stroke (PSD14), the ipsilateral thalamus demonstrated degenerating and severely damaged neurons. Staining for GFAP (astrogliosis) or IBA-1 (microgliosis) was first apparent in the ipsilateral thalamus by PSD3, and showed a progressive increase through PSD14. The number of activated microglia was increased within the thalamus at PSD14, reflecting proliferation of resident microglia as well as infiltration of peripheral monocytes. Interestingly, astrogliosis within the thalamus was enduring, as it was still evident at two years post-stroke. Furthermore, the astrogliosis at two years (but not at 6 weeks) demonstrated glial scar-like characteristics. Lastly, we demonstrated that post-stroke treatment with an NMDA receptor antagonist (memantine) reduces gliosis in the thalamus at PSD14. These findings highlight the development of lasting secondary injury in the thalamus following cortical stroke and support the value of memantine treatment in the mitigation of this injury.

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Section: Cortical Stroke Induces Neurodegeneration In Ipsilateral Thamentioning

confidence: 99%

Cortical stroke produces secondary injury and long-lasting gliosis in the ipsilateral thalamus

Kim

Stephenson

Mamun

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In the sub-acute to chronic stroke phase (e.g. beyond PSD 3), emerging lines of evidence suggest that microglia can proliferate in damaged regions of the cortex and migrate to ischemic core, where they produce a variety of cytokines and engage in cell debris clean up 28 , 29 . However, it remains to be elucidated whether the increased IBA-1 + cells in the thalamus that we and others 30 – 32 have shown reflects an increase in the proportion of activated microglia versus an increase in the total number of microglia.…”

Section: Resultsmentioning

confidence: 99%

Determining the effect of aging, recovery time, and post-stroke memantine treatment on delayed thalamic gliosis after cortical infarct

Kim

Stephenson

Mamun

et al. 2021

Sci Rep

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Secondary injury following cortical stroke includes delayed gliosis and eventual neuronal loss in the thalamus. However, the effects of aging and the potential to ameliorate this gliosis with NMDA receptor (NMDAR) antagonism are not established. We used the permanent distal middle cerebral artery stroke model (pdMCAO) to examine secondary thalamic injury in young and aged mice. At 3 days post-stroke (PSD3), slight microgliosis (IBA-1) and astrogliosis (GFAP) was evident in thalamus, but no infarct. Gliosis increased dramatically through PSD14, at which point degenerating neurons were detected. Flow cytometry demonstrated a significant increase in CD11b+/CD45int microglia (MG) in the ipsilateral thalamus at PSD14. CCR2-RFP reporter mouse further demonstrated that influx of peripheral monocytes contributed to the MG/Mϕ population. Aged mice demonstrated reduced microgliosis and astrogliosis compared with young mice. Interestingly, astrogliosis demonstrated glial scar-like characteristics at two years post-stroke, but not by 6 weeks. Lastly, treatment with memantine (NMDAR antagonist) at 4 and 24 h after stroke significantly reduced gliosis at PSD14. These findings expand our understanding of gliosis in the thalamus following cortical stroke and demonstrate age-dependency of this secondary injury. Additionally, these findings indicate that delayed treatment with memantine (an FDA approved drug) provides significant reduction in thalamic gliosis.

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“…The inflammatory response plays a significant role in brain injury, and studies have shown that activated microglia promote the release of inflammatory factors [ 24 , 25 ]. Furthermore, previous studies suggested that MRS exerted an anti-inflammatory effect in organism damage [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…Studies have shown that during reperfusion injury, large amounts of ROS were produced, which triggered microglial activation, and then activated microglia could produce proinflammatory cytokines that further aggravated brain injury by recruiting inflammatory cell aggregates [ 8 ]. On the other hand, excessive production of proinflammatory factors would also further lead to the activation of microglia, creating a vicious cycle [ 10 , 25 ]. Hayashida et al have shown that inhalation of hydrogen inhibited microglial cell activation in the hippocampus CA1 region [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Methane-Rich Saline Alleviates CA/CPR Brain Injury by Inhibiting Oxidative Stress, Microglial Activation-Induced Inflammatory Responses, and ER Stress-Mediated Apoptosis

Cui

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Brain injury induced by cardiac arrest/cardiopulmonary resuscitation (CA/CPR) is the leading cause of death among patients who have recovery of spontaneous circulation (ROSC). Inflammatory response, apoptosis, and oxidative stress are proven pathological mechanisms implicated in neuronal damage. Methane-rich saline (MRS) has been proven that exerts a beneficial protectiveness impact in several models of ischemia-reperfusion injury. The goal of this paper is to ascertain the role of MRS in CA/CPR-induced brain injury and its potential mechanisms. The tracheal intubation of Sprague-Dawley (SD) rats was clamped for 6 min to establish an asphyxiating cardiac arrest model. After that, chest compressions were applied; then, MRS or saline was administered immediately post-ROSC, the rats were sacrificed, and brain tissue was collected at the end of 6 hours. We observed that MRS treatment attenuated neuronal damage in the hippocampal CA1 region by inhibiting microglial activation, leading to a decrease in the overexpression of proinflammatory cytokines such as TNF-α, IL-6, and iNOS. The results also illustrated that MRS treatment diminished apoptosis in the hippocampal CA1 region , reduced the expression of apoptosis-associated proteins Bax and cleaved caspase9, and increased Bcl-2 expression, as well as inhibited the expression of endoplasmic reticulum (ER) stress pathway-related proteins GRP78, ATF4, and CHOP. Further findings showed that MRS treatment significantly attenuated hippocampal ROS and MDA levels and increased GSH and SOD antioxidant factor levels, which indicated that MRS treatment could inhibit oxidative stress. Our results suggest that MRS exerts a protective effect against CA/CPR brain injury, by inhibiting oxidative stress, microglial activation-induced inflammatory responses, and ER stress-mediated apoptosis.

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Microglia and Their Promising Role in Ischemic Brain Injuries: An Update

Cited by 24 publications

References 108 publications

Cortical stroke produces secondary injury and long-lasting gliosis in the ipsilateral thalamus

Cortical stroke produces secondary injury and long-lasting gliosis in the ipsilateral thalamus

Determining the effect of aging, recovery time, and post-stroke memantine treatment on delayed thalamic gliosis after cortical infarct

Methane-Rich Saline Alleviates CA/CPR Brain Injury by Inhibiting Oxidative Stress, Microglial Activation-Induced Inflammatory Responses, and ER Stress-Mediated Apoptosis

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