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Regional differences in the neuroprotective effect of minocycline in a mouse model of global forebrain ischemia

机译：米诺环素在全脑前脑缺血小鼠模型中神经保护作用的区域差异

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We investigated the effect of minocycline on neuronal damage in the hippocampus and striatum in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery (BCCAO) for 30 min. Minocycline (90 mg/kg, i.p., qd) or saline was injected immediately after BCCAO and daily for the next two days (45 mg/kg, i.p., bid). In order to reduce the variability in ischemic neuronal damage, we applied selection criteria based on regional cerebral blood flow (rCBF), evaluated using laser Doppler flowmetry, and the plasticity of the posterior communicating artery (PcomA), evaluated using India ink solution. In animals with rCBF that was less than 15% of the baseline value and with a smaller PcomA, of diameter less than one-third that of the basilar artery, we consistently observed neuronal damage in the striatum and hippocampal subfields, including medial CA1, CA2, and CA4. When the effect of minocycline was assessed with cresyl violet staining, neuronal damage in the medial part of the CA1 subfield and the striatum was found to be significantly attenuated, although minocycline did not protect against neuronal damage in the remaining hippocampal subfields. Immunohistochemistry for NeuN, adenosine A1 receptor, and SCIP/Oct-6 confirmed the region-specific effect of minocycline in the hippocampus. In summary, our results suggest that minocycline protects neurons against global forebrain ischemia in a subregion-specific manner.
机译：我们调查了短暂性前脑缺血小鼠模型中美满霉素对海马和纹状体神经元损伤的影响。用氟烷麻醉雄性C57BL / 6小鼠，并双侧阻断颈总动脉（BCCAO）30分钟。在BCCAO之后立即注射米诺环素（90 mg / kg，i.p.，每日一次）或生理盐水，随后两天每天注射（45 mg / kg，i.p.，每日两次）。为了减少局部缺血性神经元损伤的变异性，我们应用了基于局部脑血流量（rCBF）的选择标准，该标准使用激光多普勒血流仪进行了评估，而后交通动脉的可塑性（PcomA）使用了印度墨水解决方案进行了评估。在rCBF小于基线值的15％且PcomA较小，直径小于基底动脉直径的三分之一的动物中，我们始终观察到纹状体和海马子区域（包括内侧CA1，CA2）的神经元损伤和CA4。当用甲酚紫染色评估米诺环素的效果时，虽然米诺环素不能保护其余海马亚区的神经元损伤，但发现CA1子域内侧和纹状体的神经元损伤明显减弱。 NeuN，腺苷A1受体和SCIP / Oct-6的免疫组织化学证实了在海马中米诺环素具有区域特异性作用。总而言之，我们的研究结果表明，米诺环素以特定于区域的方式保护神经元免受全球前脑缺血的侵害。

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