| Autor: |
Vigil, Fabio A, Bozdemir, Eda, Bugay, Vladislav, Chun, Sang H, Hobbs, MaryAnn, Sanchez, Isamar, Hastings, Shayne D, Veraza, Rafael J, Holstein, Deborah M, Sprague, Shane M, M Carver, Chase, Cavazos, Jose E, Brenner, Robert, Lechleiter, James D, Shapiro, Mark S |
| Zdroj: |
Journal of Cerebral Blood Flow & Metabolism; Jun2020, Vol. 40 Issue 6, p1256-1273, 18p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
