Document Type
Article
Publication Date
2022
Abstract
Global cerebral ischemia/reperfusion (I/R) provokes infammation that augments neuropathic pain. Cilostazol (CLZ) has pleiotropic efects including neuroprotection in several ravaging central disorders; nonetheless, its potential role in transient central ischemic-induced allodynia and hyperalgesia has not been asserted before. Rats were allocated into 4 groups; sham, sham+CLZ, and 45 min-bilateral carotid occlusion followed by a 48 h-reperfusion period either with or without CLZ (50 mg/ kg; p.o) post-treatment. CLZ prolonged latency of hindlimb withdrawal following von Frey flaments, 4 °C cold, and noxious mechanical stimulations. Histopathological alterations and the immunoexpression of glial fbrillary acidic protein induced by I/R were reduced by CLZ in the anterior cingulate cortex (ACC) area, while, CLZ enhanced intact neuronal count. Meanwhile, CLZ modulated cerebral cortical glutamate, dopamine neurotransmission, and transient receptor potential ankyrin 1 (TRPA1). CLZ anti-infammatory potential was mediated by the downregulated p65 NF-κB and sirtuin-1 enhancement to reduce nucleotide-binding domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), active caspase-1, and interleukin-1β, indicative of infammasome deactivation. It also revealed an antioxidant capacity via boosting nuclear factor E2-related factor (Nrf2) enhancing glutathione through forkhead box protein O3a (FOXO3a) reduction. Additionally, CLZ triggered neuronal survival by promoting the p-content of Akt, TrkB, and CREB as well as BDNF content. A novel approach of CLZ in hindering global cerebral I/R–mediated neuropathy is frstly documented herein to forward its adjunct action via deactivating the NLRP3 infammasome, besides enhancing Nrf2 axis, neuronal survival, and dopamine neurotransmission as well as inhibiting TRPA1 and excitotoxicity.
Recommended Citation
Zaki, Omnia S.; Nassar, Noha N.; Abdallah, Dalaal M.; Safar, Marwa; and Mohammed, Reham A., "Cilostazol Alleviates NLRP3 Infammasome–Induced Allodynia/Hyperalgesia in Murine Cerebral Cortex Following Transient Ischemia: Focus on TRPA1/Glutamate and Akt/Dopamine/BDNF/Nrf2 Trajectories" (2022). Pharmacy. 661.
https://buescholar.bue.edu.eg/pharmacy/661