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Gene & Protein in Disease Hematoma clearance by microglia after ICH

cases worldwide, ICH affects approximately 2 million 3. Microglia and macrophage activation
people annually, and more than 50% of spontaneous ICH and function after ICH
cases occur in the basal ganglia [2-5] . With around 40% of
patients dying within 30 days after initial ictus, ICH has Microglia, as resident innate immune cells in the central
the highest mortality among all strokes, resulting in nervous system (CNS) with the ability to phagocytose, are
enormous disease and social burden [6,7] . The treatment of the first responders to brain injury, and they constitute
[17]
ICH mainly focuses on supporting therapy and managing 5%–20% of all glial cells in the adult human brain .
both symptoms and complications. Unfortunately, there is In the past, activated microglia and macrophages were
still no approved treatment for ICH [8,9] . commonly grouped as microglia/macrophages (MMΦ) as
it was difficult to differentiate them by immunohistology .
[18]
ICH leads to primary and secondary brain injury . However, in recent years, with flow cytometry, microglia
[10]
Within the first hour following blood vessel rupture, can be identified by the CD11b CD45 phenotype, while
+
int
hematoma forms, and expands with a resulting mass monocyte-derived macrophages can be identified by the
effect, leading to primary brain injury [8,11] . In contrast, the CD11b CD45 high F4/80 Ly6c phenotype [19-21] . Microglia
-
+
+
blood degradation products released from the hematoma, are amoeba-like cells that can migrate to the damaged
microglial/macrophage activation with the release of site and activate when pathological changes disrupt brain
pro-inflammatory molecules, and infiltrated blood homeostasis [22,23] . After microglial activation, monocyte-
immunocytes all contribute to secondary brain injury derived macrophages infiltrate the perihematomal
after ICH [12-14] . Consequently, hematoma removal is a region [20,24,25] . Established anti-inflammatory markers
potential treatment option to prevent secondary injury increase on day 1, with a significant increase on day 3,
cascades. However, surgical removal of the hematoma and a further increase on day 7 . Hemorrhagic injury to
[19]
has not shown to significantly increase the survival rate the brain contributes to prominent microglial activation,
of patients or promote the neurological recovery of characterized by increased ionized calcium-binding
survivors . adaptor molecule 1 (Iba1) and CD11b expression as well as
[15]
[26]
Treatment with potential neuroprotective agents thick and short cell processes .
identified to protect against secondary injury has not Microglia are highly diverse and have dual effect on
produced satisfactory functional recovery in patients with the brain during inflammation. Through transcriptome
[16]
ICH . We aim to summarize the progress of microglial analysis, surveillant microglia, homeostasis-associated
activation and function after ICH by highlighting the microglia, axon-associated microglia, highly activated
dual role of microglia and microglial-specific markers microglia, synapse-associated microglia, and virus-
since it can be targeted to mitigate secondary brain injury associated microglia have been identified in the
and improve brain repair and recovery. Furthermore, CNS [27-29] . Clinical and preclinical studies have shown
we outline the time course of changes in the molecular that there is microglial heterogeneity across specific brain
markers of microglia activation after ICH and emphasize regions in terms of morphology, density, gene expression,
the phagocytic function of microglia. Finally, we discuss and proliferation. Although it is not fully understood,
the underlying mechanism of hematoma clearance by evidence has indicated that microglia play a unique role
microglia after ICH. This review will help us better in different brain regions . However, two microglial
[30]
understand the role of microglia in hematoma clearance activation states, which include the pro- and anti-
after ICH and identify potential therapeutic targets to inflammatory phenotypes, still predominate in stroke and
facilitate translational research in this direction. ICH . Although recent studies have shown that microglial
[26]
activation states are much more complex than these two
2. Literature search strategy and selection phenotypes, we can use these two terms for convenience
criteria of description . However, we suggest focusing more on
[31]
For this review, we searched PubMed for articles published microglial function than on phenotype alone.
between April 19, 2016, and January 6, 2023, using the The molecular markers identifying the pro-
terms “ICH,” “inflammation,” “hematoma clearance,” inflammatory phenotype include inducible nitric oxide
“Microglial/macrophage,” “Anti-inflammation,” “IL-10,” synthase (iNOS), CD68, CD16/32, and CD86, while
“phagocytosis,” and “molecular markers.” We used English arginase 1 (ARG1), CD206, CD163, FIZZ1, YM1, and
search words and included papers published with English CD36 are the molecular markers that characterize the
abstracts. We selected articles describing microglial anti-inflammatory phenotype after ICH . Very recent
[26]
activation and function as well as hematoma clearance research has shown that transmembrane protein 119
mechanisms after ICH. (TMEM119), Fc receptor-like S (FCRLS), olfactomedin-

Volume 2 Issue 2 (2023) 2 https://doi.org/10.36922/gpd.336