The Neuroprotective Effects Of Cannabinoid And Its Mechanisms In Rats With Intracerebral Hemorrhage

Background and Objective: Intracerebral hemorrhage is clinical common emergency severe syndrome. Some studies show that cell apoptosis involved in the process of tissue injury surrounding hematoma[1]. In central nervous system (CNS), Cannabinoids(CBs)can be broadly defined as compounds with actions on cannabinoid receptorⅠto protect the neurons[4]. The endocannabinoids (eCBs) and related lipids accumulate in ischemic tissues supporting the hypothesis that the ECS is activated during ischemia[2 3].Activation of the CB1 cannabinoid receptor results a decrease in the probability of opening of voltage-operated calcium channels [5 6 7] and inhibition of glutamate release [8]. In addition, the CB1 receptor activation produces vasodilation[9 10 11]and hypothermia[12].In this study ,we investigated the intervention effect of WIN55,212-2 on experimental intracerebral hemorrhage in rats, to research if WIN55,212-2 has the protective effect on cerebral injury caused by hematoma and brain edema surrounding hematoma in intracerebral hemorrhage, and to explore its possible protection mechanism. Biochemical pathways or cytoprotective cellular mechanisms that triggered by apoptotic CB receptor against can be differentially delay cell death[4]. Methods: The rats were divided into sham group, model group, WIN55,212-2 low(1μg·g^-1), middle (3μg·g^-1), high (5μg·g^-1) dose groups and nimodipine positive control group randomly. The rat intracerebral hemorrhage model was established by injecting collagenase VII with microinjector into the globus pallidus of brain. The sham group rats were only injected normal saline into the globus pallidus of brain, not bleeding. The medicines or anequal volume of vehicle (DMSO and saline) were injected by the intraperitoneal route (i.p.), 30 min after ICH. We observed the effect of WIN55,212-2 on the ethologic change of ICH rat and pathologic change of ipsilateral cerebral tissues of ICH brain. And the cerebral tissue pathomorphology was observed in HE staining by microscope .The localizations of PKAC-β, C-FOS and BDNF were assessed by immunohistochemistry. The expressions of PKAC-β, C-FOS and BDNF mRNA were detected by RT-PCR. The expressions of PKAC-βand BDNF protein were revealed by Western blot to explore the possible protection mechanism of WIN55,212-2.Results:(1)WIN55,212-2 can promote the neurons recovery process of rat after ICH and can improve pathological morphology of rat brain after ICH. WIN55, 212-2 increased not only the levels of BDNF mRNA and protein, but also C-FOS mRNA in ipsilateral cerebral cortex,in a dose dependent manner. However, it decreased the levels of PKAC-βmRNA and protein. PKAC-β, C-FOS, and BDNF proteins were expressed on membrane of neurons, nucleus of neurons or the cytoplasm of glial cells respectively. Conclusions: WIN55,212-2 induces the expression of BDNF in the cerebral cortex, it may be a theoretical basis for treating the injured neurons of cerebrovascular disease.