Abd Aziz Noor Azliza Wani, Iezhitsa Igor, Agarwal Renu, Bakar Nor Salmah, Abd Latiff Azian, Ismail Nafeeza Mohd
From the Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia.
Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia.
J Neuropathol Exp Neurol. 2022 Jul 19;81(8):596-613. doi: 10.1093/jnen/nlac047.
Given the neuroprotective effects of trans-resveratrol (RV), this study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in RV-mediated neuroprotection in a rat intracerebral hemorrhage (ICH) model induced by intrastriatal injection of collagenase. Rats were divided into 5 groups: (1) control, (2) sham-operated, (3) ICH pretreated with vehicle, (4) ICH pretreated with RV, and (5) ICH pretreated with RV and the A1R antagonist DPCPX. At 48 hours after ICH, the rats were subjected to neurological testing. Brain tissues were assessed for neuronal density and morphological features using routine and immunohistochemical staining. Expression of tumor necrosis factor-α (TNF-α), caspase-3, and RIPK3 proteins was examined using ELISA. A1R, MAPK P38, Hsp90, TrkB, and BDNF genes were examined using RT-qPCR. RV protected against neurological deficits and neuronal depletion, restored the expression of TNF-α, CASP3, RIPK3, A1R, and Hsp90, and increased BDNF/TrkB. DPCPX abolished the effects of RV on neurological outcomes, neuronal density, CASP3, RIPK3, A1R, Hsp90, and BDNF. These data indicate that the neuroprotection by RV involves A1R and inhibits CASP3-dependent apoptosis and RIPK3-dependent necroptosis in the perihematoma region; this is likely to be mediated by crosstalk between A1R and the BDNF/TrkB pathway.
鉴于反式白藜芦醇（RV）具有神经保护作用，本研究旨在探讨腺苷A1受体（A1R）在由纹状体内注射胶原酶诱导的大鼠脑出血（ICH）模型中RV介导的神经保护作用中的参与情况。将大鼠分为5组：（1）对照组，（2）假手术组，（3）用溶剂预处理的ICH组，（4）用RV预处理的ICH组，以及（5）用RV和A1R拮抗剂DPCPX预处理的ICH组。ICH后48小时，对大鼠进行神经功能测试。使用常规染色和免疫组织化学染色评估脑组织的神经元密度和形态特征。使用酶联免疫吸附测定法检测肿瘤坏死因子-α（TNF-α）、半胱天冬酶-3和RIPK3蛋白的表达。使用逆转录定量聚合酶链反应（RT-qPCR）检测A1R、丝裂原活化蛋白激酶P38（MAPK P38）、热休克蛋白90（Hsp90）、酪氨酸激酶受体B（TrkB）和脑源性神经营养因子（BDNF）基因。RV可预防神经功能缺损和神经元减少，恢复TNF-α、CASP3、RIPK3、A1R和Hsp90的表达，并增加BDNF/TrkB。DPCPX消除了RV对神经功能结局、神经元密度、CASP3、RIPK3、A1R、Hsp90和BDNF的影响。这些数据表明，RV的神经保护作用涉及A1R，并抑制血肿周围区域中半胱天冬酶-3依赖性凋亡和RIPK3依赖性坏死性凋亡；这可能是由A1R与BDNF/TrkB途径之间的相互作用介导的。
