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Gene & Protein in Disease Hematoma clearance by microglia after ICH

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Figure 1. Intracerebral hemorrhage (ICH)-induced brain injury and microglial and macrophage activation. (A) ICH is caused by the rupture of small
arterial. The subsequent formation and expansion of hematoma and the mass effect lead to primary brain injury, which initiates the release of blood
components and innate immune responses, resulting in secondary brain injury. (B) There are two activation states of microglia/macrophages (MMΦ):
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pro-inflammatory phenotype (ionized calcium-binding adaptor molecule 1 [Iba1 ] and CD16/32 ) and anti-inflammatory phenotype (Iba1 , CD206 ,
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CD36 , and triggering receptor expressed on myeloid cells 2 [TREM2 ]). Pro-inflammatory microglia release cytokines such as tumor necrosis factor
alpha, interleukin 6 (IL-6), IL-12, and IL-1β, while anti-inflammatory microglia release transforming growth factor beta, IL-4, IL-10, and IL-13. Although
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CD68 , TREM2 , galectin-3 [GAL-3 ], and CD11c have been found to be expressed by reactive phagocytic microglia in the aged brain, only a few studies
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have explored phagocytic microglial markers in the ICH brain. After ICH, there is a change in microglial phenotype from the pro-inflammatory phenotype
in the acute phase to a broad spectrum of phenotypes in the subacute stage. Ultimately, the anti-inflammatory phenotype predominates at the injury site
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in the chronic stage of ICH (TREM2 ?: the role of TREM2 in hematoma clearance is unknown).
neurologic deficits related to delayed hematoma clearance. IL-10 may enhance microglial phagocytosis by
However, 2 h after ICH, daily intranasal administration of upregulating the expression of CD68, GAL-3, CD11, and
mouse recombinant IL-10 improved hematoma clearance microglial phagocytic receptors, including TREM2, in the
and mitigated neurologic deficits. In addition, IL-10- aged brain [38,58] . However, no studies have explored their
deficient mice had decreased phagocytic capacity due to role in ICH models, particularly in clearing hematoma.
low microglial CD36 levels, and IL-10 deficiency markedly However, a clinical study has shown that, compared to
increased monocyte-derived macrophage infiltration and patients with unfavorable outcome, patients with favorable
brain inflammation. From these results, we concluded that outcome had significantly higher serum and hematoma
IL-10 improves microglial phagocytosis and monocyte- IL-10 levels. At the same time, binary logistic analysis
derived macrophage infiltration and CD36 plays a crucial has revealed that increased IL-10 levels in serum and
role as a phagocytosis effector regulated by IL-10 after hematoma were associated with favorable outcome in
ICH . patients with ICH on day 90 . Combined with evidence
[45]
[59]
Volume 2 Issue 2 (2023) 5 https://doi.org/10.36922/gpd.336