Neuronal kinase SGK1.1 protects against brain damage after status epilepticus

Epilepsy is a neurological condition associated to significant brain damage produced by (SE) including neurodegeneration, gliosis and ectopic neurogenesis. Reduction of these processes constitutes a useful strategy to improve recovery and ameliorate negative outcomes after an initial insult. SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), has been shown to increase M-current density in neurons, leading to reduced excitability and protection against seizures. We now show that SGK1.1 activation potently reduces levels of neuronal death and gliosis after SE induced by kainate, even in the context of high seizure activity. This neuroprotective effect is not exclusively a secondary effect of M-current activation but is also directly linked to decreased apoptosis levels through regulation of Bim and Bcl-x cellular levels. Our results demonstrate that this newly described antiapoptotic role of SGK1.1 activation acts synergistically with the regulation of cellular excitability, resulting in a significant reduction of SE-induced brain damage. The protective role of SGK1.1 occurs without altering basal neurogenesis in brain areas relevant to epileptogenesis.