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 CB1
R 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
R 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 CB1
R. Considerable evidences have indicated that CB1
R 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 CB1
Rs takes an important part in cerebral ischemic injury. PKC and CB1
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.
R -mediated activation of PKCε can effectively stimulate ischemic tolerance.
R 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
R and neuron injuries, to target the receptor will exert neuroprotective effects on
cerebral ischemia, which provides wide foreground for a novel therapy target.