MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats.

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

作为一种内质网应激诱导蛋白，中脑星形胶质细胞源性神经营养因子（MANF）已被证明可保护多巴胺能神经元和非多巴胺能细胞。我们先前的研究表明，MANF可抵御缺血/再灌注损伤。在此，我们开发了一种磁共振成像（MRI）技术，以动态评估MANF对缺血/再灌注损伤的治疗效果。我们采用大脑中动脉闭塞法（MCAO）建立了大鼠局灶性缺血模型。通过MRI研究病变形成的动态过程。在MCAO 90分钟后再灌注3小时，根据MRI检测首次出现明显病变时，将MANF蛋白注射到右侧脑室。在再灌注后第1、2、3、5和7天，对缺血/再灌注损伤大鼠进行用于评估MANF蛋白治疗效果的T2加权成像，并结合组织学方法。结果表明，在缺血/再灌注损伤后的早期给予MANF蛋白可降低死亡率，改善神经功能，减少脑梗死体积，并减轻脑组织损伤。从MRI获得的结果与形态学和病理学变化一致，这表明MRI是一种用于评估药物治疗效果的有用技术。