Abd Aziz Noor Azliza Wani, Iezhitsa Igor, Agarwal Renu, Abdul Kadir Roqiah Fatmawati, Abd Latiff Azian, Ismail Nafeeza Mohd
Centre for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia.
Centre of PreClinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia.
Neurol Res. 2020 Mar;42(3):189-208. doi: 10.1080/01616412.2020.1716470. Epub 2020 Feb 4.
-resveratrol has been shown to have neuroprotective effects and could be a promising therapeutic agent in the treatment of intracerebral haemorrhage (ICH). This study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in -resveratrol-induced neuroprotection in rats with collagenase-induced ICH. Sixty male Sprague-Dawley rats weighing 330-380 g were randomly divided into five groups (n = 12): (i) control, (ii) sham-operated rats, (iii) ICH rats pretreated with vehicle (0.1% DMSO saline, i.c.v.), (iv) ICH rats pretreated with -resveratrol (0.9 µg, i.c.v.) and (v) ICH rats pretreated with -resveratrol (0.9 µg) and the A1R antagonist, DPCPX (2.5 µg, i.c.v.). Thirty minutes after pretreatment, ICH was induced by intrastriatal injection of collagenase (0.04 U). Forty-eight hours after ICH, the rats were assessed using a variety of neurobehavioural tests. Subsequently, rats were sacrificed and brains were subjected to gross morphological examination of the haematoma area and histological examination of the damaged area. Severe neurobehavioural deficits and haematoma with diffuse oedema were observed after intrastriatal collagenase injection. Pretreatment with -resveratrol partially restored general locomotor activity, muscle strength and coordination, which was accompanied with reduction of haematoma volume by 73.22% (P < 0.05) and damaged area by 60.77% (P < 0.05) in comparison to the vehicle-pretreated ICH group. The -resveratrol-induced improvement in neurobehavioural outcomes and morphological features of brain tissues was inhibited by DPCPX pretreatment. This study demonstrates that the A1R activation is possibly the mechanism underlying the -resveratrol-induced neurological and neurobehavioural protection in rats with ICH.
白藜芦醇已被证明具有神经保护作用，可能是治疗脑出血（ICH）的一种有前景的治疗药物。本研究旨在探讨腺苷A1受体（A1R）在白藜芦醇诱导的胶原酶诱导脑出血大鼠神经保护中的作用。将60只体重330 - 380 g的雄性Sprague-Dawley大鼠随机分为五组（n = 12）：（i）对照组，（ii）假手术组大鼠，（iii）用载体（0.1%二甲基亚砜盐水，脑室内注射）预处理的ICH大鼠，（iv）用白藜芦醇（0.9 μg，脑室内注射）预处理的ICH大鼠，以及（v）用白藜芦醇（0.9 μg）和A1R拮抗剂DPCPX（2.5 μg，脑室内注射）预处理的ICH大鼠。预处理30分钟后，通过纹状体内注射胶原酶（0.04 U）诱导ICH。ICH后48小时，使用多种神经行为测试对大鼠进行评估。随后，处死大鼠，对大脑进行血肿区域的大体形态学检查和损伤区域的组织学检查。纹状体内注射胶原酶后观察到严重的神经行为缺陷和伴有弥漫性水肿的血肿。与载体预处理的ICH组相比，白藜芦醇预处理部分恢复了一般运动活动、肌肉力量和协调性，同时血肿体积减少了73.22%（P < 0.05），损伤区域减少了60.77%（P < 0.05）。DPCPX预处理抑制了白藜芦醇诱导的神经行为结果改善和脑组织形态特征改善。本研究表明，A1R激活可能是白藜芦醇诱导ICH大鼠神经和神经行为保护的潜在机制。
