HGF/cMet Activation Improves Neurocognitive Deficits After Repeated TBI
Poster Abstract
Traumatic brain injury (TBI) is a significant healthcare issue with no FDA-approved treatment. Over 75% of TBIs are categorized as mild TBI that can result in persistent impairments of attention, memory, and motor functions. Additionally, young adults have a high incidence of repeated mild TBI. Repeated injuries increase the brain's vulnerability to further insult and produce more severe cognitive and behavioral dysfunction. Such, impaired cognitive and motor functions contribute to a reduced quality of life and longer return to employment, education, or sport for approximately 1.6-3.8 million individuals each year in the United States.
The brain hepatocyte growth factor (HGF) system is critical for the development and maintenance of the central nervous system (CNS). HGF and its receptor, cMET, are expressed in cortical and hippocampal areas involved in attention, memory, and sensorimotor functions. Activation of the HGF/c-Met pathway in the CNS has been shown to be both neuroprotective and procognitive following ischemic injury and models of neurodegeneration. We posit that HGF/c-Met activation after repetitive mild TBI may rescue cognitive impairments, specifically spatial working memory and sensorimotor function. We found that dihexa, a potentiator of HGF/cMET, dose-dependently rescued TBI-induced impairments in a delayed alternation task of working memory. These findings demonstrate that cMET activation is sufficient and necessary for dihexa’s rescue of working memory impairments following repeated mild TBI and indicate a potential role for HGF/c-Met activation in the treatment of the behavioral and cognitive deficits caused by repeated mild TBI.
HGF/cMet Activation Improves Neurocognitive Deficits After Repeated TBI
Traumatic brain injury (TBI) is a significant healthcare issue with no FDA-approved treatment. Over 75% of TBIs are categorized as mild TBI that can result in persistent impairments of attention, memory, and motor functions. Additionally, young adults have a high incidence of repeated mild TBI. Repeated injuries increase the brain's vulnerability to further insult and produce more severe cognitive and behavioral dysfunction. Such, impaired cognitive and motor functions contribute to a reduced quality of life and longer return to employment, education, or sport for approximately 1.6-3.8 million individuals each year in the United States.
The brain hepatocyte growth factor (HGF) system is critical for the development and maintenance of the central nervous system (CNS). HGF and its receptor, cMET, are expressed in cortical and hippocampal areas involved in attention, memory, and sensorimotor functions. Activation of the HGF/c-Met pathway in the CNS has been shown to be both neuroprotective and procognitive following ischemic injury and models of neurodegeneration. We posit that HGF/c-Met activation after repetitive mild TBI may rescue cognitive impairments, specifically spatial working memory and sensorimotor function. We found that dihexa, a potentiator of HGF/cMET, dose-dependently rescued TBI-induced impairments in a delayed alternation task of working memory. These findings demonstrate that cMET activation is sufficient and necessary for dihexa’s rescue of working memory impairments following repeated mild TBI and indicate a potential role for HGF/c-Met activation in the treatment of the behavioral and cognitive deficits caused by repeated mild TBI.