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Updated: Jul 15, 2026
A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
A microglial kinase ITK mediating neuroinflammation and behavioral deficits in traumatic brain injury
Ruqayya Afridi1, Anup Bhusal2, Seung Eun Lee3
1Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Abstract:
Microglia-mediated neuroinflammation has been implicated in the neuropathology of traumatic brain injuries (TBI). Recently, the expression of interleukin-2-inducible T-cell kinase (ITK) has been detected in brain microglia, regulating their inflammatory activities. However, the role of microglial ITK in TBI has not been investigated. In this study, we demonstrate that ITK expression and activation are upregulated in microglia following an injury caused by controlled cortical impact (CCI) - a mouse model of TBI. Pharmacological inhibition of ITK protein or knockdown of microglial ITK gene expression using adeno-associated virus mitigates neuroinflammation and improves neurological outcomes in the CCI model. Additionally, ITK mRNA expression was found to be increased in the brains of patients with chronic traumatic encephalopathy. An ITK inhibitor reduced the activation of inflammatory responses in both human and mouse microglia in vitro. Collectively, these results suggest that microglial ITK plays a pivotal role in neuroinflammation and mediating behavioral deficits following TBI. Thus, targeting the signaling pathway of microglial ITK may exert protective effects by alleviating neuroinflammation associated with TBI.
Insights
Interleukin-2-inducible T-cell kinase (ITK) in microglia drives neuroinflammation after traumatic brain injury (TBI). Inhibiting microglial ITK reduces inflammation and improves outcomes in TBI models.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation driven by microglia is central to traumatic brain injury (TBI) pathology.
- Interleukin-2-inducible T-cell kinase (ITK) regulates microglial inflammatory responses but its role in TBI is unknown.
Purpose of the Study:
- To investigate the role of microglial ITK in TBI pathogenesis.
- To evaluate ITK as a potential therapeutic target for TBI.
Main Methods:
- Utilized a controlled cortical impact (CCI) mouse model of TBI.
- Assessed ITK expression and activation in microglia post-injury.
- Employed pharmacological ITK inhibition and gene knockdown (AAV-mediated) in vivo.
- Examined ITK mRNA in human chronic traumatic encephalopathy (CTE) brains.
- Tested ITK inhibitor effects on human and mouse microglia in vitro.
Main Results:
- ITK expression and activation were upregulated in microglia following CCI.
- ITK inhibition or knockdown ameliorated neuroinflammation and improved neurological function in the CCI model.
- Increased ITK mRNA was observed in human CTE brains.
- ITK inhibition reduced inflammatory responses in both human and mouse microglia.
Conclusions:
- Microglial ITK is a key mediator of neuroinflammation and behavioral deficits in TBI.
- Targeting microglial ITK signaling offers a promising therapeutic strategy for TBI by reducing neuroinflammation.
