title: Protective effects of bupivacaine against kainic acid-induced seizure and neuronal cell death in the rat hippocampus.
abstract: The excessive release of glutamate is a critical element in the neuropathology of epilepsy, and bupivacaine, a local anesthetic agent, has been shown to inhibit the release of glutamate in rat cerebrocortical nerve terminals. This study investigated whether bupivacaine produces antiseizure and antiexcitotoxic effects using a kainic acid (KA) rat model, an animal model used for temporal lobe epilepsy, and excitotoxic neurodegeneration experiments. The results showed that administering bupivacaine (0.4 mg/kg or 2 mg/kg) intraperitoneally to rats 30 min before intraperitoneal injection of KA (15 mg/kg) increased seizure latency and reduced the seizure score. In addition, bupivacaine attenuated KA-induced hippocampal neuronal cell death, and this protective effect was accompanied by the inhibition of microglial activation and production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the hippocampus. Moreover, bupivacaine shortened the latency of escaping onto the platform in the Morris water maze learning performance test. Collectively, these data suggest that bupivacaine has therapeutic potential for treating epilepsy.
authors.affiliation: Division of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital; 2. Department of Nursing, Oriental Institute of Technology Pan-Chiao District, New Taipei City 22061, Taiwan.
authors.forename: Kuan Ming
authors.initials: KM
authors.lastname: Chiu
authors.forename: Chia Chan
authors.initials: CC
authors.lastname: Wu
authors.forename: Ming Jiuh
authors.initials: MJ
authors.lastname: Wang
authors.forename: Ming Yi
authors.initials: MY
authors.lastname: Lee
authors.forename: Su Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002045:Bupivacaine / Q000494:pharmacology / Q000627:therapeutic use*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007608:Kainic Acid; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007608:Kainic Acid; D002045:Bupivacaine