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Modulation of the balance between cannabinoid CB(1) and CB(2) receptor activation during cerebral ischemic/reperfusion injury.
Neuroscience 2008; 152(3):753-60N

Abstract

Cannabinoid receptor activation has been shown to modulate both neurotransmission (CB(1)) and neuroinflammatory (CB(2)) responses. There are conflicting reports in the literature describing the influence of cannabinoid receptor activation on ischemic/reperfusion injury. The goal of this study was to evaluate how changing the balance between CB(1) and CB(2) activation following cerebral ischemia influences outcome. CB(1) and CB(2) expression were tested at different times after transient middle cerebral artery occlusion (MCAO) in mice by real-time RT-PCR. Animals subjected to 1 h MCAO were randomly assigned to receive different treatments: a CB(1) antagonist, a CB(2) antagonist, a CB(2) agonist, a CB(1) antagonist plus CB(2) agonist, a CB(2) antagonist plus CB(2) agonist or an equal volume of vehicle as control. Cerebral blood flow was continuously monitored during ischemia; cerebral infarction and neurological deficit were tested 24 h after MCAO. Cerebral CB(1) and CB(2) mRNA expression undertook dynamic changes during cerebral ischemia. The selective CB(1) antagonist significantly decreased cerebral infarction by 47%; the selective CB(2) antagonist increased infarction by 26% after 1 h MCAO followed by 23 h reperfusion in mice. The most striking changes were obtained by combining a CB(1) antagonist with a CB(2) agonist. This combination elevated the cerebral blood flow during ischemia and reduced infarction by 75%. In conclusion, during cerebral ischemia/reperfusion injury, inhibition of CB(1) receptor activation is protective while inhibition of CB(2) receptor activation is detrimental. The greatest degree of neuroprotection was obtained by combining an inhibitor of CB(1) activation with an exogenous CB(2) agonist.

Authors+Show Affiliations

Center for Substance Abuse Research, Temple University School of Medicine, 231 OMS, 3400 North Broad Street, Philadelphia, PA 19140, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18304750

Citation

Zhang, M, et al. "Modulation of the Balance Between Cannabinoid CB(1) and CB(2) Receptor Activation During Cerebral Ischemic/reperfusion Injury." Neuroscience, vol. 152, no. 3, 2008, pp. 753-60.
Zhang M, Martin BR, Adler MW, et al. Modulation of the balance between cannabinoid CB(1) and CB(2) receptor activation during cerebral ischemic/reperfusion injury. Neuroscience. 2008;152(3):753-60.
Zhang, M., Martin, B. R., Adler, M. W., Razdan, R. K., Ganea, D., & Tuma, R. F. (2008). Modulation of the balance between cannabinoid CB(1) and CB(2) receptor activation during cerebral ischemic/reperfusion injury. Neuroscience, 152(3), pp. 753-60. doi:10.1016/j.neuroscience.2008.01.022.
Zhang M, et al. Modulation of the Balance Between Cannabinoid CB(1) and CB(2) Receptor Activation During Cerebral Ischemic/reperfusion Injury. Neuroscience. 2008 Mar 27;152(3):753-60. PubMed PMID: 18304750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of the balance between cannabinoid CB(1) and CB(2) receptor activation during cerebral ischemic/reperfusion injury. AU - Zhang,M, AU - Martin,B R, AU - Adler,M W, AU - Razdan,R K, AU - Ganea,D, AU - Tuma,R F, Y1 - 2008/01/25/ PY - 2007/10/09/received PY - 2008/01/04/revised PY - 2008/01/14/accepted PY - 2008/2/29/pubmed PY - 2008/7/22/medline PY - 2008/2/29/entrez SP - 753 EP - 60 JF - Neuroscience JO - Neuroscience VL - 152 IS - 3 N2 - Cannabinoid receptor activation has been shown to modulate both neurotransmission (CB(1)) and neuroinflammatory (CB(2)) responses. There are conflicting reports in the literature describing the influence of cannabinoid receptor activation on ischemic/reperfusion injury. The goal of this study was to evaluate how changing the balance between CB(1) and CB(2) activation following cerebral ischemia influences outcome. CB(1) and CB(2) expression were tested at different times after transient middle cerebral artery occlusion (MCAO) in mice by real-time RT-PCR. Animals subjected to 1 h MCAO were randomly assigned to receive different treatments: a CB(1) antagonist, a CB(2) antagonist, a CB(2) agonist, a CB(1) antagonist plus CB(2) agonist, a CB(2) antagonist plus CB(2) agonist or an equal volume of vehicle as control. Cerebral blood flow was continuously monitored during ischemia; cerebral infarction and neurological deficit were tested 24 h after MCAO. Cerebral CB(1) and CB(2) mRNA expression undertook dynamic changes during cerebral ischemia. The selective CB(1) antagonist significantly decreased cerebral infarction by 47%; the selective CB(2) antagonist increased infarction by 26% after 1 h MCAO followed by 23 h reperfusion in mice. The most striking changes were obtained by combining a CB(1) antagonist with a CB(2) agonist. This combination elevated the cerebral blood flow during ischemia and reduced infarction by 75%. In conclusion, during cerebral ischemia/reperfusion injury, inhibition of CB(1) receptor activation is protective while inhibition of CB(2) receptor activation is detrimental. The greatest degree of neuroprotection was obtained by combining an inhibitor of CB(1) activation with an exogenous CB(2) agonist. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18304750/Modulation_of_the_balance_between_cannabinoid_CB_1__and_CB_2__receptor_activation_during_cerebral_ischemic/reperfusion_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(08)00101-2 DB - PRIME DP - Unbound Medicine ER -