Fasudil a novel potential treatment for controlling Traumatic brain injury (TBI)

RHO kinase inhibitors (ROCKs) belong to the serine-threonine kinase family, which plays a pivotal role in regulating the damage, survival, axon guidance, and regeneration of neurons.[۱] Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. 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. [۵]Materials and methods: Data were collected from the Scopus, Google Scholar, PubMed, and Cochrane libraries for clinical, in vivo, and in vitro studies published in English between ۱۹۹۲-۲۰۲۲.Results: ROCKs activity is present in many types of nerve cells in the CNS. Excess ROCKs activity in the CNS leads to oxidative stress, uncontrolled inflammation, immune abnormality, energy metabolism disorder, neuronal cell loss, reactive gliosis, and impaired synaptic transmission, thus promoting the development of neurodegenerative diseases.Discussion: Fasudil, the first ROCKs inhibitor to be used clinicall . Fasudil is mainly used for the short-term treatment of vasospasm after subarachnoid hemorrhage. It has a good therapeutic effect on neurodegenerative diseases, but its relatively narrow safety window and lack of an orally administered formulation limit its long-term clinical application. Due to some specific side effects of ROCK inhibitors when administered systemically, including hypotension, skin reactions, and reversible renal dysfunction, delivery of ROCK inhibitors via topical application has been considered.Fasudil has limited selectivity with respect to ROCKs and may also act on other kinases at therapeutic concentrations. However, inhibition of other kinases may also contribute to the beneficial effects of Fasudil, particularly in CNS disorders Fasudil increases the activity of neural stem cells and BMSCs (Bone Marrow Mesenchymal Stem Cells), thus optimizing cell therapy and combination of BMSCs and fasudil provides a promising method for the treatment of ischemic stroke and other TBIs.[۴]Environmental enrichment combined with fasudil improve motor function, increase growth-associated protein ۴۳ in the infarcted cerebral cortex, promote axonal regeneration , and downregulated ROCK, p-LIM domain kinase (LIMK)۱, and p-cofilin expression. Environmental enrichment combined with fasudil treatment promotes motor recovery after TBIs, partially by stimulating axonal regeneration. The underlying mechanism involve ROCK/LIMK۱/cofilin pathway regulation.[۳]Conclusions: Fasudil is a BBB protective agent against Traumatic brain injury (TBI).[۲] and this is a novel potential treatment, especially in combination with cell-based therapy.Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments.Although, inhibiting RhoA-ROCK signaling has emerged as a promising approach for treating CNS disorders.[۵] But The etiologies of neurodegenerative diseases are complex and involve many signaling pathways for which the cellular and molecular mechanisms are not clear; thus, suppression of the ROCKs signaling pathway is not sufficient for disease treatment. So It is necessary to further clarify the cellular and molecular mechanisms of the pathogenesis of neurodegenerative diseases and test combinations of drugs to achieve therapeutic effects by blocking different signaling pathways. and this is an important future research direction.[۱](BBB)

کلیدواژه ها:

RHO kinase inhibitor ، Fasudil ، Traumatic brain injury (TBI) ، Blood Brain Barrier(BBB)