TY  - JOUR
PY  - 2019//
TI  - Prevention of brain damage after traumatic brain injury by pharmacological enhancement of KCNQ (Kv7, "M-type") K+ currents in neurons
JO  - Journal of cerebral blood flow and metabolism
A1  - Vigil, Fabio A.
A1  - Bozdemir, Eda
A1  - Bugay, Vladislav
A1  - Chun, Sang H.
A1  - Hobbs, MaryAnn
A1  - Sanchez, Isamar
A1  - Hastings, Shayne D.
A1  - Veraza, Rafael J.
A1  - Holstein, Deborah M.
A1  - Sprague, Shane M.
A1  - Carver, Chase M.
A1  - Cavazos, Jose E.
A1  - Brenner, Robert
A1  - Lechleiter, James D.
A1  - Shapiro, Mark S.
SP  - 0271678X1985781
EP  - 0271678X1985781
VL  - 
IS  - 
N2  - Nearly three million people in the USA suffer traumatic brain injury (TBI) yearly; however, there are no pre- or post-TBI treatment options available. KCNQ2-5 voltage-gated K+ channels underlie the neuronal "M current", which plays a dominant role in the regulation of neuronal excitability. Our strategy towards prevention of TBI-induced brain damage is predicated on the suggested hyper-excitability of neurons induced by TBIs, and the decrease in neuronal excitation upon pharmacological augmentation of M/KCNQ K+ currents. Seizures are very common after a TBI, making further seizures and development of epilepsy disease more likely. Our hypothesis is that TBI-induced hyperexcitability and ischemia/hypoxia lead to metabolic stress, cell death and a maladaptive inflammatory response that causes further downstream morbidity. Using the mouse controlled closed-cortical impact blunt TBI model, we found that systemic administration of the prototype M-channel "opener", retigabine (RTG), 30 min after TBI, reduces the post-TBI cascade of events, including spontaneous seizures, enhanced susceptibility to chemo-convulsants, metabolic stress, inflammatory responses, blood-brain barrier breakdown, and cell death. This work suggests that acutely reducing neuronal excitability and energy demand via M-current enhancement may be a novel model of therapeutic intervention against post-TBI brain damage and dysfunction.     Keywords Cell death, K+ channels, KCNQ, seizures, traumatic brain injury<p />  <p>Language: en</p>
LA  - en
SN  - 0271-678X
UR  - http://dx.doi.org/10.1177/0271678X19857818
ID  - ref1
ER  -