title: Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.
abstract: Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh 160014, India.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.affiliation: School of Studies in Neuroscience, Jiwaji University, Gwalior 474011, Madhya Pradesh, India.
authors.forename: Ishan
authors.initials: I
authors.lastname: Patro
authors.affiliation: National Institute of Pharmaceutical Education and Research, Mohali 160062, Punjab, India.
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh 160014, India. Electronic address: sandhir@pu.ac.in.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D003474:Curcumin
keywords: Curcumin; Cytokines; Epilepsy; Glia; Neuroinflammation; Pentylenetetrazole