Expression of the Endocannabinoid Receptor 1 in Human Stroke: An Autoptic Study

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• 作者：Paola Caruso ; MD ; ^{caruso.paola1983@libero.it" class="auth_mail" title="E-mail the corresponding author} ; Marcello Naccarato ; MD ; PhD ; Valentina Faoro ; Danae Pracella ; Marta Borando ; MD ; Isabella Dotti ; Nadia Koscica ; MD ; Giorgio Stanta ; MD ; Gilberto Pizzolato ; MD ; Paolo Manganotti ; MD
• 关键词：Ischemic stroke ; cannabinoid receptors ; inflammation ; autoptic study ; ischemic core ; penumbra
• 刊名：Journal of Stroke and Cerebrovascular Diseases
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：25
• 期：9
• 页码：2196-2202
• 全文大小：933 K

文摘

Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved. Our aim was to evaluate the cerebral expression of CB1R in the ischemic brain areas of 9 patients who died due to acute cerebral infarction in the middle cerebral artery territory.

Methods

The cerebral autoptic tissue was collected within 48 hours since death. Ischemic and contralateral normal-appearing areas were identified. After tissue preprocessing, 4-µm-thick cerebral sections were incubated with the primary CB1R antibodies (Cayman Chemical Company, Ann Arbor, MI). Thereafter, all cerebral sections were hematoxylin treated. In each section, the total cell number and CB1R-positive cells were counted and the CB1R-positive cell count ratio was calculated. For statistical analysis, Student's t-test was used.

Results

In normal tissue, CB1R-positive neurons were the majority; a few non-neuronal cells expressed CB1R. In the ischemic areas, a few neurons were detectable. A significant increase in total CB1R staining was found in the ischemic regions compared to contralateral areas.

Conclusions

We found an increase in CB1R expression in the ischemic region (neuronal and non-neuronal cell staining), suggesting the inflammatory reaction to the ischemic insult. Whether such response might mediate neuroprotective actions or excitotoxicity-related detrimental effects is still unclear.