Src Family Kinase Inhibitors and their Role in the Treatment of Traumatic Brain Injuries

Abstract

Traumatic brain injury (TBI) leads to a broad spectrum of neurological deficits, including cognitive impairments that are irreversible and significantly influence quality of life even after recovery from physical disabilities. Clinically, there is no standardized procedure for treating secondary TBI, as each case is symptomatic. Src family kinase (SFK) inhibitors, a relatively new treatment regarding TBI, have so far been neuroprotective against secondary damage in non-human models. Immediately after TBI, there is increased expression of NR2A and NR2B. SFKs regulate NR2 subunits of NMDARs through tyrosine phosphorylation. Synthetic inhibitors of SFKs may help reduce the cognitive dysfunction seen after TBI by binding to SFKs and inhibiting the tyrosine phosphorylation of NMDARs, thereby preventing excitotoxicity within neurons that leads to cell death.