Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia

Title:Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia

Volume: 17 Issue: 2

Author(s): Quankun Zhuang, Cailing Dai, Linglong Yang, Huimin Wen, Hongyun Wang, Xiaoxue Jiang and Yuyang Zhang*

Affiliation:

• Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016,China

Keywords: Anandamide, cannabinoid receptor, cerebral ischemia, ischemic tolerance, neuroprotection, molecular events.

Abstract: Background: It is reported that endogenous cannabinoids can cause vasodilation and bradycardia. They have anti-inflammatory effect and protect endothelial cells from injury, therefore they have potential application prospect in the prevention of cardio-cerebrovascular diseases. However, the mechanisms of the neuroprotection mediated by cannabinoid 1 receptors (CB₁Rs) have not been uncovered in detail.

Methods: Nearly one hundred of new publications relevant to the theme are almost selected from Pubmed. The advanced details associated with the involvement of CB₁R in cerebral ischemia as well as cerebral ischemic tolerance are reviewed.

Results: Anandamide system is mainly made up of cannabinoid receptors, their endogenous ligands and some related enzymes. The activation of the system mediates various molecular events so that plays a crucial role in the neuroprotection of cerebral ischemia. Increasing evidences suggest that CB₁R is one of key molecules that mediate cerebral ischemia and cerebral ischemia tolerance. It is likely to provide an appropriate antioxidant balance by increasing endogenous free radical scavengers and helpful to exert the neuroprotective effects. Moreover, MAPKs, including ERK1/2, c-Jun Nterminal kinase (JNK) and p38MAPK can be recruited and stimulated through a complex signaling networks mediated by CB₁R. Considerable evidences have indicated that CB₁R was a crucial regulator for ERK1/2 signaling pathway. It is known that PI3K/Akt is a classical signaling pathway and its activation exerts neuroprotective effect via significant promoting cell survival. Glycogen synthase kinase-3β (GSK-3β) is an important downstream target of p-Akt. The PI3K/Akt/GSK-3β signaling pathway mediated by CB₁Rs takes an important part in cerebral ischemic injury. PKC and CB₁R are found to be abundantly co-expressed in presynaptic nerve endings of brain. There are considerable reports that different PKC isozymes played vital roles respectively in cerebral ischemic injury and preconditioning. The CB₁R -mediated activation of PKCε can effectively stimulate ischemic tolerance.

Conclusion: CB₁R played an important part via several signaling pathways in the protection from ischemic stroke and in ischemic tolerance. The involved molecular signaling pathways include ERK1/2, PI3K/Akt/GSK-3β and the translocation and activation of PKCε. With the intimate association between CB₁R and neuron injuries, to target the receptor will exert neuroprotective effects on cerebral ischemia, which provides wide foreground for a novel therapy target.

Cite this article as:

Zhuang Quankun, Dai Cailing, Yang Linglong, Wen Huimin, Wang Hongyun, Jiang Xiaoxue and Zhang Yuyang*, Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia, Central Nervous System Agents in Medicinal Chemistry 2017; 17 (2) . https://dx.doi.org/10.2174/1871524916666160504104624

DOI https://dx.doi.org/10.2174/1871524916666160504104624	Print ISSN 1871-5249
Publisher Name Bentham Science Publisher	Online ISSN 1875-6166