TRPV1 Contributes to the Neuroprotective Effect of Dexmedetomidine in Pilocarpine-Induced Status Epilepticus Juvenile Rats.

Abstract

To investigate the antiepileptic and neuroprotective effects of dexmedetomidine (Dex) in pilocarpine- (Pilo-) induced status epilepticus (SE) juvenile rats, rats were randomly assigned to the following six groups (n = 20): normal, normal+Dex, SE, SE+Cap, SE+Dex, and SE+Dex+Cap. The rats were treated with either diazepam (i.p., an antiepileptic drug) or Dex after the onset of SE. The Morris water maze was used to assess rat cognitive behavior. Flow cytometry was used to detect the concentrations of Ca2+, mitochondrial membrane potential, and reactive oxygen species. Transmission electron microscopy was performed to evaluate specimens of brain tissue. The levels of caspase 3 and TRPV1 were examined by western blot and immunohistochemistry (IHC). Treatment with Dex significantly decreased the escape latency of the SE rats (P < 0.05). Capsaicin, a TRPV1 agonist, delivery aggravated the performance of SE rats. Pathological changes in SE rat were attenuated by Dex and deteriorated by capsaicin. Swollen mitochondria and abnormal endoplasmic reticulum were found in SE rats and were then aggravated by capsaicin and reversed by Dex. Moreover, our data showed that Dex significantly restrained calcium overload, ROS production, and mitochondrial membrane potential loss, all of which were induced by Pilo and capsaicin (P < 0.05). Dex decreased the apoptotic rate in the Model SE group (P < 0.05) and TRPV1 and caspase 3 expression in the Dex treatment group (P < 0.05). Interestingly, all these effects of Dex were partially counteracted by the TRPV1 agonist, capsaicin (P < 0.05). Our study showed that Dex exerted a neuroprotective effect in Pilo-induced SE rats by inhibiting TRPV1 expression and provided information for therapy to SE patients.

• Authors: Xingqin Tan, Yong Zeng, Zhenzhen Tu, Pan Li, Hengsheng Chen, Li Cheng, Shengfen Tu, Li Jiang
• Journal: BioMed research international (Biomed Res Int) Vol. 2020 Pg. 7623635 ( 2020) ISSN: 2314-6141 [Electronic] United States
• PMID: 32337274 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Xingqin Tan et al.

Chemical References

• Neuroprotective Agents
• Reactive Oxygen Species
• TRPV Cation Channels
• Trpv1 protein, rat
• Pilocarpine
• Dexmedetomidine
• Casp3 protein, rat
• Caspase 3
• Calcium

Topics

• Animals
• Apoptosis (drug effects)
• Calcium (metabolism)
• Caspase 3 (metabolism)
• Dexmedetomidine (pharmacology)
• Disease Models, Animal
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Neuroprotective Agents (pharmacology)
• Pilocarpine (adverse effects)
• Rats
• Reactive Oxygen Species (metabolism)
• Status Epilepticus (chemically induced, drug therapy, pathology)
• TRPV Cation Channels (metabolism)