Selected Papers: Laboratory Studies

Authors: Obara, Soichi; Imamura, Shin-ichi; Akaike, Koichi; Tanaka, Shigeya; Maruyama, Ikuro; Kuratsu, Jun-ichi; Iwai, Hiromasa; Komatsu, Mitsuaki; Shiota, Go; Honjoe, Nobuyuki; Kubota, Yukiko; Ishii, Yoshio; Watanabe, Kazuhiro; Kogure, Shinichi; Hayashi, Naoki; Mikuni, Nobuhiro; Hayase, Yoneko; Amano, Shigeru; Miura, Yoshiki; Miyamoto, Susumu; Takahashi, Jun; Hashimoto, Nobuo; Sato, Keiko; Iwai, Masanori; Zhang, Wen-Ri; Kamada, Hiroshi; Ohta, Kentaro; Omori, Nobuhiko; Nagano, Isao; Shoji, Mikio; Abe, Koji; Hiramatsu, Midori; Higuchi, Yoshihiro; Tanii, Hideji; Ishii, Yasuko; Shigeru, Oowada; Takazawa, Akira; Kitano, Yutaka; Kinoshita, Masakazu; Komiyama, Chika; Yamauchi, Toshio; Okamoto, Motoi; Sakiyama, Junko; Mori, Shuji; Usui, Shinichi; Sasa, Masashi; Yan, Hai-Dun; Ishihara, Kumatoshi; Nagayama, Takashi; Serikawa, Tadao; Murashima, Yoshiya L.; Yoshii, Mitunobu; Suzuki, Jiro; Ishimaru, Yuji; Chiba, Shigeru; Omori, Nobuyuki; Takasaki, Hideki; Tabata, Kazuki; Ishimoto, Takahiro; Tamura, Yoshiyuki; Kiura, Yoshihiro; Hanaya, Ryosuke; Kurisu, Kaoru

Source: Epilepsia, Volume 46, Supplement 1, March 2005 , pp. 91-95(5)

Publisher: Wiley-Blackwell

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Abstract:

An Endogenous Cannabinoid (2-AG) Is Neuroprotective Against Limbic Seizures in Rats.

<namegroup type="author"> <name type="author"> *† <forenames>Soichi</forenames> <surname>Obara</surname> </name>, <name type="author"> * <forenames>Shin-ichi</forenames> <surname>Imamura</surname> </name>, <name type="author"> ‡ <forenames>Koichi</forenames> <surname>Akaike</surname> </name>, <name type="author"> § <forenames>Shigeya</forenames> <surname>Tanaka</surname> </name>, <name type="author"> † <forenames>Ikuro</forenames> <surname>Maruyama</surname> </name>, and <name type="author"> * <forenames>Jun-ichi</forenames> <surname>Kuratsu</surname> </name> ( <address type="affiliation" format="inline">Departments of <address><spannew id="a143"> Neurosurgery </spannew></address>, <address><spannew id="a144"> Laboratory and Molecular Medicine </spannew></address> and <address><spannew id="a145"> Neuropsychiatry, University of Kagoshima, Faculty of Medicine </spannew></address>, and <address><spannew id="a146"> Tanaka Neurosurgical Clinic, Kagoshima, Japan </spannew></address>). </address> </namegroup> Purpose: Prior studies indicated that 2-arachidonoglycerol (2-AG), an endogenous cannabinoid, might have neurophysiologic effects on the hippocampus, possibly by activating cannabinoid receptor-1 (CB1). This study was designed to clarify the effect of 2-AG on hippocampal neuronal damages caused by kainic acid (KA)-induced limbic seizures. Methods: Twenty-four rats underwent stereotactic implantation of electrodes in the left amygdala (LA), left hippocampus (LH), and left sensorimotor cortex (LCx). A stainless steel cannula also was introduced into the LA and LH. The animals then were divided into four groups according to the pretreatment agent infused into LH: sham control [dimethyl sulfoxide (DMSO); 1 μl, n = 6], KA control (DMSO; 1 μl, n = 6), group A (2-AG; 100 μM, n = 6), and group B [2-AG (100 μM) + SR-141716A (a CB-1 antagonist; 10 μM), n = 6]. After 10 min, all rats except the sham-treated group received 1 μg of kainic acid (KA) via the cannula. Sham-treated rats received phosphate-buffered saline (PBS) instead. After electroclinical observation for 7 days, histologic examination and statistical analysis were performed. Results: In KA controls, immediate multiple spike discharges in LA propagated concurrently to the LH. The propagation involved the LCx, with development of status epileptics 1–2 h after KA injection. Seizures were characterized by mastication, salivation, facial twitching, forelimb clonus, and sometimes rearing and falling, and lasted 1–2 days. Microscopic examination revealed severe neuronal cell damage in the LA and LH. In group A, seizure discharges were eliminated overall and neuronal cell damage in LH was reduced compared with the KA controls. Rats in group A only showed behavioral changes such as wet-dog shake. In group B, seizure discharges and neuronal cell damage in LH were virtually the same as in controls. Sham-treated rats showed no electroclinical and histologic changes. Conclusions: These results indicate that the 2-AG exhibits a neuroprotective effect against limbic seizures by activating CB1.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.0013-9580.2005.t01-12-20050228.x

Publication date: 2005-03-01

Selected Papers: Laboratory Studies

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