| First Author | Kim TY | Year | 2017 |
| Journal | Brain Res | Volume | 1655 |
| Pages | 138-144 | PubMed ID | 27840189 |
| Mgi Jnum | J:260381 | Mgi Id | MGI:6148147 |
| Doi | 10.1016/j.brainres.2016.11.009 | Citation | Kim TY, et al. (2017) Analysis of the protective effects of the alpha2/delta subunit of voltage-gated Ca(2+) channels in brain injury. Brain Res 1655:138-144 |
| abstractText | Voltage-gated Ca(2+) channels (VGCCs) are comprised of alpha1, alpha2/delta, beta, and gamma subunits. The pore-forming alpha1 subunit is essential for the proper functioning of Ca(2+) channels, while the alpha2/delta subunit interacts with components of the extracellular matrix. The alpha2/delta subunit is related in many neuropathological symptoms, including epilepsy and cerebellar ataxia. We previously reported that the mutant Cav.2.1alpha1 subunit has protective effects following brain injury. The present study aimed to investigate the effects of the alpha2/delta subunit inhibition alone and in combination with the inhibition of the Cav.2.1alpha1 subunit following brain injury by injecting Gabapentin using Cav.2.1alpha1 mutant heterozygous rolling Nagoya (rol/+) and wild-type (+/+) mice. Gabapentin binds to the alpha2/delta subunit and leads to Ca(2+) flow disturbance. A cryogenic method was used to induce brain injury. The mice pretreated with 100mg/kg Gabapentin exhibited a decrease in lesion size, while the 40mg/kg Gabapentin injection was effective in rol/+ mice but not +/+ mice. The administration of 100mg/kg Gabapentin also attenuated reactive astrocyte activity and neuronal degeneration; the pattern of results was similar to that for lesion size. An analysis of phosphorylated p38 (pp38) expression revealed that Gabapentin suppressed the p38 mitogen-activated protein kinase (MAPK) signaling cascade by interrupting glutamate-signaling induced by the inhibition of VGCCs. The present findings demonstrated that the administration of the alpha2/delta subunit inhibitor, Gabapentin, had neuroprotective effects following brain injury. |
