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MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats
Xian-Yun Wang1, Meng-Meng Song2,3, Si-Xing Bi4
1The First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230032, China. xyunwang1991@163.com.
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.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) protein administration early after stroke reduced mortality and improved neurological function. Magnetic resonance imaging (MRI) effectively monitored these therapeutic effects in a rat model.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Medical Imaging
Background:
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-inducible protein known to protect neurons.
- Previous research demonstrated MANF's protective effects against ischemia/reperfusion (I/R) injury.
Purpose of the Study:
- To develop and utilize magnetic resonance imaging (MRI) technology for dynamically evaluating the therapeutic effects of MANF on cerebral ischemia/reperfusion (I/R) injury.
- To assess the efficacy of early-stage MANF protein administration in a rat focal ischemic model.
Main Methods:
- A rat focal ischemic model was established using middle cerebral artery occlusion (MCAO).
- MRI was employed to monitor lesion development and evaluate therapeutic effects using T2-weighted imaging.
- MANF protein was administered intracerebroventricularly 3 hours post-reperfusion.
- Histology methods were used for correlation and validation.
Main Results:
- Early administration of MANF protein significantly decreased mortality rates in I/R injury rats.
- MANF treatment led to improved neurological function and reduced cerebral infarct volume.
- MRI findings correlated well with histological and pathological changes, confirming reduced brain tissue injury.
Conclusions:
- MANF protein is a promising therapeutic agent for early-stage treatment of ischemia/reperfusion injury.
- MRI is a valuable tool for dynamically assessing the therapeutic efficacy of drugs in stroke models.
- Early intervention with MANF can mitigate the detrimental effects of cerebral ischemia.
