Afridi, Ruqayya Bhusal, Anup Lee, Seung Eun Hwang, Eun Mi Ryu, Hoon Kim, Jong-Heon Suk, Kyoungho 2025-03-22T13:00:11Z 2025-03-22T13:00:11Z 2025-03-19 2025-03 1044-7431 https://pubs.kist.re.kr/handle/201004/151997 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. English Academic Press A microglial kinase ITK mediating neuroinflammation and behavioral deficits in traumatic brain injury Article 10.1016/j.mcn.2025.103994 1 Molecular and Cellular Neuroscience, v.132 Molecular and Cellular Neuroscience 132 N scie scopus 001414891800001 2-s2.0-85216187961 Neurosciences Neurosciences & Neurology Article INFLAMMATION ACTIVATION TEC Traumatic brain injury Microglia Interleukin-2-inducible T -cell kinase Neuroinflammation