Abstract
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.
Highlights
Stroke is a very common cause of death and disability in the middle-aged and aged populations worldwide [1]
In Hoffer’s research, recombinant human mesencephalic astrocyte-derived neurotrophic factor (MANF) was pretreated in middle cerebral artery occlusion (MCAO) rats, and the results indicated that the infarction volume was reduced significantly 2 days after MCAO [13]
32 rats divided in 3 groups were used for mortality statistics: 18 rats were treated with MANF at 10 μg (n = 9) or 20 μg (n = 9), and the remaining rats were treated with PBS
Summary
Stroke is a very common cause of death and disability in the middle-aged and aged populations worldwide [1]. 87% are ischemic strokes resulting from a disruption in cerebral blood flow in a major brain artery [2]. Tissue plasminogen activator (t-PA) has been proved to be effective for acute ischemic stroke by intravenous administration [3]. This agent can be used in a very narrow therapeutic window and has some hazardous complications (such as myocardial infarction). Only few patients can benefit from it [4,5]. It is urgently needed to develop new potential treatments for ischemic stroke
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