Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice
Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice
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DOI：
10.1211/jpp.60.6.0008
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Chakrabarti, Amitava
中科院分区：
文献类型：
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作者：
Aggarwal, Raman;Medhi, Bikash;Chakrabarti, Amitava
研究了黄体酮（一种类固醇激素）对双侧颈总动脉闭塞（BCAO）引起的脑缺血小鼠模型急性时相变化的可能神经保护作用。该研究共有 72 只雄性小鼠。采用BCAO模型诱导部分全脑缺血。形态学评估包括梗塞面积和脑水肿的测量。使用亚惊厥剂量的戊四唑（30 mg kg(-1) i.p.）评估缺血后癫痫发作的易感性。生化评估包括肿瘤坏死因子α (TNF-α) 水平和酶参数，例如脂质过氧化、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶以及蛋白质评估。 BCAO 在盐水处理的对照组中引起显着的梗死面积和水肿，同时氧化应激增加，表现为脂质过氧化增加和抗氧化剂（如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）水平降低。与对照组相比，黄体酮（15 mg kg(-1) i.p.）给药可显着减少脑梗塞面积，从而显示出神经保护作用。随着阳性反应者数量的减少，缺血后癫痫发作的易感性也降低。脑水肿消退，但不明显。与缺血组相比，黄体酮显着降低了 TNF-α 水平。黄体酮提高了所有抗氧化剂的水平，表明其具有对抗 BCAO 诱导的氧化应激的活性。结果证明了黄体酮对缺血性损伤的神经保护作用，表明类固醇作为神经保护剂的作用。
The possible neuroprotective effect of progesterone, a steroid hormone, on acute phase changes in a mouse model of cerebral ischaemia induced by bilateral common carotid artery occlusion (BCAO) was studied. A total of 72 male mice were included in the study. The BCAO model was used to induce partial global cerebral ischaemia. Morphological assessment included measurement of infarct size and brain oedema. Post-ischaemic seizure susceptibility was assessed using a subconvulsive dose of pentylenetetrazole (30 mg kg(-1) i.p.). Biochemical estimations included tumour necrosis factor alpha (TNF-alpha) levels and enzyme parameters such as lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase, and protein estimation. BCAO induced a significant infarct size and oedema in the saline-treated control group, along with an increase in oxidative stress, indicated by increased lipid peroxidation and decreased levels of antioxidants such as superoxide dismutase, catalase and glutathione peroxidase. Progesterone (15 mg kg(-1) i.p.) administration showed a neuroprotective effect by significantly reducing the cerebral infarct size as compared with the control group. Post-ischaemic seizure susceptibility was also reduced as the number of positive responders decreased. Brain oedema subsided, but not significantly. Progesterone significantly reduced TNF-alpha levels compared with the ischaemia group. Progesterone improved levels of all the antioxidants, indicating activity against oxidative stress induced by BCAO. The results demonstrate the neuroprotective effect of progesterone against ischaemic insult, suggesting a role for the steroid as a neuroprotective agent.