AN ENDOGENOUS CANNABINOID (2-AG) IS NEUROPROTECTIVE FOR LIMBIC SEIZURES IN RATS
Abstract number :
1.020
Submission category :
Year :
2002
Submission ID :
1519
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Shin-ichi Imamura, Soichi Obara, Koichi Akaike, Shigeya Tanaka, Ikuro Maruyama, Jun-ichi Kuratsu. Neurosurgery, University of Kagoshima, Faculty of Medicine, Kagoshima, Kagoshima, Japan; Laboratory and Molecular Medicine, University of Kagoshima, Faculty
RATIONALE: Prior studies indicated that 2-Arachidonoyl glycerol (2-AG), an endogenous cannabinoid, might have neurophysiologic roles to hippocampus possibly by activating cannabinoid receptor-1 (CB1). This study was designed to clarify the effect of 2-AG on hippocampal neuronal damage induced 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 the 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 agents infused into LH; sham (phosphate-buffered saline solution (PBS), 1.0 microL, n=6), controls (PBS, 1.0 microL, n=6), group A (2-AG, 100 microM, n=6), and group B (2-AG, 100 microM+AM251 (CB1 antagonist), 100 microM, n=6). 2-AG and AM251 were dissolved in dimethyl sulphoxide. After 10 minutes, rats except shams received 1microgram of kainic acid (KA) into LA via the cannula. Shams received PBS alone into the LA. After 7 days of electroclinical observation, histologic examination and statistic analysis were made.
RESULTS: In controls, multiple spike discharges in LA immediately propagated concurrently to the LH. Propagation involved the LCx to become status epilepticus 1 to 2 hours after KA injection. Seizures, characterized by mastication, salivation, facial twitching, forelimb clonus, and sometimes rearing and falling, lasted 1 to 2 days. Microscopic examination revealed severe neuronal cell damage in the LA and LH. Unlike controls, overall seizure discharges were eliminated and neuronal cell damage in LH were reduced in group A. They only showed behavioral changes such as wet dog shaking. In group B, seizure discharges and neuronal cell damages in LH were virtually the same as controls. Shams showed no electroclinical and histological changes.
CONCLUSIONS: These results suggest that 2-AG acts neuroprotectivelyby activating CB1 in KA-indeuced limbic siezures.
[Supported by: Grant[ndash]in-Aid for Encouragement of Young Scientists from the Ministry of Education, Sciences, and Culture of Japan; grant from the La Salle High School Graduates[ssquote] Association (Medical Division in Kagoshima).]