دورية
The sodium channel blocker RS100642 reverses down-regulation of the sodium channel α-subunit Nav1.1 expression caused by transient ischemic brain injury in rats
| العنوان: | The sodium channel blocker RS100642 reverses down-regulation of the sodium channel α-subunit Nav1.1 expression caused by transient ischemic brain injury in rats |
|---|---|
| المؤلفون: | Yao, C., Williams, A. J., Lu, X. -C. M., Price, R. A., Cunningham, B. S., Berti, R., Tortella, F. C., Dave, J. R. |
| المصدر: | Neurotoxicity Research; January 2003, Vol. 5 Issue: 4 p245-253, 9p |
| مستخلص: | In this study we evaluated the expression of five sodium channel (NaCh) α-subunit genes after transient middle cerebral artery occlusion (MCAo) in the rat and the effects of treatment with the NaCh blocker and experimental neuroprotective agent RS100642 as compared to the prototype NaCh blocker mexiletine. The expression of Nav1.1, Nav1.2, Nav1.3, Nav1.7, Nav1.8 and the housekeeping gene β-actin were studied in vehicle or drug-treated rats at 6, 24 and 48 h post-MCAo using real-time quantitative RT-PCR. RS100642 (1 mg/kg), mexiletine (10 mg/kg), or vehicle (1 ml/kg) was injected (i.v.) at 30 min, 2, 4, and 6 h post-injury. Following MCAo only the Nav1.1. and Nav1.2 genes were significantly down-regulated in the ipsilateral hemisphere of the injured brains. RS100642 treatment significantly reversed the down-regulation of Nav1.1 (but not Nav1.2) at 24–48 h post-injury. Mexiletine treatment, on the other hand, had no significant effect on the down-regulation of either gene. These findings demonstrate that treatment with a neuroprotective dose of RS100642 significantly reverses the down-regulation of Nav1.1 caused by ischemic brain injury and suggests that RS100642 selectively targets the Nav1.1 α-subunit of the NaCh. Furthermore, our findings strengthen the hypothesis that ischemic injury may produce selective depletion of voltage-gated NaChs, and suggest that the Nav 1.1 NaCh α-subunit may play a key role in the neuronal injury/recovery process. |
| قاعدة البيانات: | Supplemental Index |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 10298428 14763524 |
|---|---|
| DOI: | 10.1007/BF03033382 |