TY - JOUR
T1 - Δ9-tetrahydrocannabinol (Δ9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia
AU - Hayakawa, Kazuhide
AU - Mishima, Kenichi
AU - Nozako, Masanori
AU - Hazekawa, Mai
AU - Ogata, Ayumi
AU - Fujioka, Masayuki
AU - Harada, Kazuhiko
AU - Mishima, Shohei
AU - Orito, Kensuke
AU - Egashira, Nobuaki
AU - Iwasaki, Katunori
AU - Fujiwara, Michihiro
N1 - Funding Information:
Part of this study was supported by a Grant-in-Aid for Scientific Research (No.17590479) from the Ministry of Education, Science and Culture of Japan, the Naito Foundation and the Advanced Materials Institute of Fukuoka University.
PY - 2007/3/27
Y1 - 2007/3/27
N2 - Δ9-tetrahydrocannabinol (Δ9-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB1 receptor. In this study, Δ9-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Δ9-THC was completely abolished by SR141716, cannabinoid CB1 receptor antagonist, and by warming the animals to 31 °C. Δ9-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 °C. At 24 h after cerebral ischemia, Δ9-THC significantly increased the expression level of CB1 receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 °C during 4 h cerebral ischemia did not increase the expression of CB1 receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Δ9-THC is mediated by a temperature-dependent mechanism via the CB1 receptor. In addition, warming to 31 °C might attenuate both the neuroprotective and hypothermic effects of Δ9-THC through inhibiting the increase in CB1 receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Δ9-THC.
AB - Δ9-tetrahydrocannabinol (Δ9-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB1 receptor. In this study, Δ9-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Δ9-THC was completely abolished by SR141716, cannabinoid CB1 receptor antagonist, and by warming the animals to 31 °C. Δ9-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 °C. At 24 h after cerebral ischemia, Δ9-THC significantly increased the expression level of CB1 receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 °C during 4 h cerebral ischemia did not increase the expression of CB1 receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Δ9-THC is mediated by a temperature-dependent mechanism via the CB1 receptor. In addition, warming to 31 °C might attenuate both the neuroprotective and hypothermic effects of Δ9-THC through inhibiting the increase in CB1 receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Δ9-THC.
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U2 - 10.1016/j.lfs.2007.01.014
DO - 10.1016/j.lfs.2007.01.014
M3 - Article
C2 - 17289082
AN - SCOPUS:33947161433
SN - 0024-3205
VL - 80
SP - 1466
EP - 1471
JO - Life Sciences
JF - Life Sciences
IS - 16
ER -