October 18, 2021

Cleaning the Brain After Ischemic Stroke
A group led by researchers from the University of Tsukuba identified the role of cell
receptor CD300a in the elimination of damaged cells in the brain following ischemic
strokeTsukuba, Japan – It’s clear that taking out the trash is an essential process inmaintaining a clean and tidy home. But did you know that your body has a similar
process for waste removal in which damaged cells are “thrown out”? A research team inJapan has recently shed new light on the dynamics of this process—termedefferocytosis—following ischemic stroke.
In a new study published this month in Science Immunology, researchers from theUniversity of Tsukuba use a mouse model to identify the role of a key cell receptor,
CD300a, in the process of efferocytosis after stroke.
During ischemic stroke, blockage of a blood vessel supplying the brain leads to
disrupted blood flow, which can trigger cell death. Dying cells in turn trigger inflammatory
responses that may worsen damage in the brain and lead to neurological impairment.
Therefore, the elimination of dying cells through efferocytosis is a key part of minimizing
the effects of ischemic stroke. However, the process of efferocytosis is not fully
understood. The group led by researchers from the University of Tsukuba sought tofurther clarify the role of efferocytosis in ischemic stroke, particularly in the super-acutephase, which occurs within hours of the initial onset of stroke.
“We focused on cell receptor CD300a because it has been shown to be involved inefferocytosis, but its particular role in the process is not entirely clear,” explains seniorauthor Professor Akira Shibuya. “We thought that it might represent a potential target toreduce the damage caused by ischemic stroke.”
To investigate the role of CD300a in efferocytosis following stroke, researchers induced
ischemic stroke in a mouse model that was deficient in CD300a and found that CD300adeficient mice showed less neurological deficits in the super-acute phase of stroke
compared with stroke-induced mice that had normal CD300a expression. These effects
appeared to be the result of enhanced efferocytosis in the CD300a-deficient mice,illustrating the role of CD300a in the inhibition of efferocytosis.
The researchers also found that treatment with an antibody that blocked the action ofCD300a in mice with normal CD300a expression led to a reduction in brain inflammation
after stroke, and that these mice even showed enhanced recovery following the blockingtreatment.

“Our findings demonstrate the importance of efferocytosis during the super-acute phaseof stroke and the impact of CD300a on the regulation of this process,” says Professor
Shibuya.
Because ischemic stroke may cause harmful neurological effects in the brain, strategies
to reduce cellular damage and inflammation following stroke are of great importance.
Blocking the action of CD300a to promote the removal of damaged cells throughefferocytosis may be a potential means to reduce damage after ischemic stroke.
The article, “CD300a blockade enhances efferocytosis by infiltrating myeloid cells andameliorates neuronal deficit after ischemic stroke,” was published in Science
Immunology at DOI: 10.1126/sciimmunol.abe7915
Funding: This study was supported by JSPS KAKENHI 16H06387 (A.S.), 18H05022(A.S.), 21H04836 (A.S.), and 19H03766 (C.N.-O.) and Takeda Science Foundation(C.N.-O.).
Summary Researchers from the University of Tsukuba identify the role of cell receptor
CD300a in efferocytosis, a process by which dead cells are eliminated from the body.
Mice deficient in CD300a exhibited an increase in efferocytosis in the brain following theinduction of stroke and treatment with a CD300a-blocking antibody lessened the severityof neurological symptoms in stroke-induced mice. CD300a may represent a potential
target for therapy in the treatment of ischemic stroke.
Tweet Garbage day for dying cells? Researchers at the University of Tsukuba shed newlight on the process of waste removal in the brain following ischemic stroke
Primary Keyword: Health and medicine
Additional Keywords: Neurological disorders, Ischemia, Brain ischemia, Inflammatory
signaling, Myeloid cells