Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBIs, which range in severity from mild to severe, occur when a traumatic event, such as a fall, a traffic accident, or a blow, causes the brain to move rapidly within the skull, resulting in damage. Long-term consequences of TBI can include motor and cognitive deficits and emotional disturbances that result in a reduced quality of life and work productivity. Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments. Central nervous system (CNS) injury and disease are known to induce the activation of the small GTPase RhoA and its downstream effector Rho kinase (ROCK). Activation of this signaling pathway promotes cell death and the retraction and loss of neural processes and synapses, which mediate information flow and storage in the brain. Thus, inhibiting RhoA-ROCK signaling has emerged as a promising approach for treating CNS disorders. In this review, we discuss targeting the RhoA-ROCK pathway as a therapeutic strategy for treating TBI and summarize the recent advances in the development of RhoA-ROCK inhibitors.
Highlights
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Primary brain injury happens at the time of the initial trauma due to direct mechanical damage, whereas secondary injury develops over time as a consequence of destructive biochemical cascades associated with excitotoxicity, perturbed calcium homeostasis, free radical production, mitochondrial dysfunction, and inflammation [8]
Previous work in the retina has shown that ROCK inhibition preserves rod-bipolar synapses after retinal detachment [70]. We investigated this possibility and found that blocking RhoA-ROCK signaling with fasudil treatment prevents Traumatic brain injury (TBI)-induced pathological spine remodeling in mice subjected to CCI injury [43]
Summary
Traumatic brain injury (TBI) is a major health problem that affects approximately 2.8 million people in the United States each year and contributes to around 30% of all injury-related deaths [1]. In addition to lifelong impairments in learning, memory, and attention, TBI survivors often suffer from depression, anxiety, and personality changes [2,3]. These issues affect individuals and have adverse effects on family members and communities. Sports-related TBIs, which are common in adolescents and young adults and often go unreported, pose a particular problem since recurrent head injuries increase the risk of developing a progressive neurodegenerative disorder known as chronic traumatic encephalopathy (CTE) [4,5]. RhoA and its major downstream effector Rho-associated kinase (ROCK/ROK/Rho-kinase) as potential promising therapeutic targets to treat TBI
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
