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Updated: Jul 16, 2025
A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
CD22 blockade modulates microglia activity to suppress neuroinflammation following intracerebral hemorrhage
Honglei Ren1, Yan Pan1, Danni Wang1
1Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Tianjin Medical University General Hospital, Tianjin 300052, China.
Abstract:
Microglia are first responders to acute brain insults and initiate neuroinflammation to drive secondary tissue injury. Yet the key molecular switches in control of the inflammatory activity of microglia remain poorly understood. Intracerebral hemorrhage (ICH) is a devastating stroke subtype whereby a hematoma is formed within the brain parenchyma and associated with high mortality. Using a mouse model of ICH, we found upregulation of CD22 that predominantly occurred in microglia. Antibody blockade of CD22 led to a reduction in neurological deficits, brain lesion and hematoma volume. This was accompanied by reduced inflammatory activity, increased expression of alternative activation markers (CD206 and IL-10) and enhanced phagocytosis activity in microglia after ICH. CD22 blockade also led to an increase of phosphorylated SYK and AKT after ICH. Notably, the benefits of CD22 blockade were ablated in ICH mice subjected to microglial depletion with a colony-stimulating factor 1 receptor inhibitor PLX5622. Additionally, the protective effects of CD22 blockade was diminished in ICH mice receiving a SYK inhibitor R406. Together, our findings highlight CD22 as a key molecular switch to control the detrimental effects of microglia after acute brain injury, and provide a novel strategy to improve the outcome of ICH injury.
Insights
Blocking CD22 in microglia reduces brain damage after intracerebral hemorrhage (ICH). This approach lessens inflammation and improves outcomes in a mouse model, offering a new therapeutic strategy for stroke.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Microglia, the brain's immune cells, are crucial in neuroinflammation following acute brain injury.
- The molecular mechanisms controlling microglial inflammatory responses after intracerebral hemorrhage (ICH) are not fully understood.
- ICH is a severe stroke subtype with high mortality, necessitating novel therapeutic targets.
Purpose of the Study:
- To investigate the role of CD22 in microglial activation and inflammatory responses after ICH.
- To evaluate the therapeutic potential of CD22 blockade in a mouse model of ICH.
Main Methods:
- Utilized a mouse model of intracerebral hemorrhage (ICH).
- Administered antibody blockade of CD22.
- Assessed neurological deficits, brain lesion volume, hematoma size, microglial activation markers, and downstream signaling pathways (SYK, AKT).
Main Results:
- CD22 was upregulated in microglia following ICH.
- CD22 blockade significantly reduced neurological deficits, brain lesion, and hematoma volume.
- Treatment decreased inflammatory activity, increased alternative activation markers (CD206, IL-10), and enhanced microglial phagocytosis.
- CD22 blockade's efficacy was dependent on microglia and involved SYK signaling.
Conclusions:
- CD22 acts as a critical molecular switch regulating detrimental microglial activity post-ICH.
- Targeting CD22 represents a promising therapeutic strategy to mitigate brain damage and improve outcomes after ICH.
- This study provides a novel approach for managing acute brain injury.
