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Published on: May 4, 2015
Effect of Methylene Blue on White Matter Injury after Ischemic Stroke
Quancheng Cheng1, Xuhao Chen2, Jiayi Ma2
1Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing 100191, China.
Abstract:
Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.
Insights
Methylene blue (MB) shows neuroprotective effects in ischemic stroke by reducing brain damage and improving neurological function, even when administered 24 hours post-stroke. It also protects white matter, suggesting broader therapeutic potential.
Area of Science:
- Neuroscience
- Pharmacology
- Stroke Research
Background:
- Methylene blue (MB) is an FDA-approved drug with demonstrated neuroprotective properties in ischemic stroke models.
- The precise mechanisms underlying MB's protective effects, particularly concerning white matter, remain largely unelucidated.
Purpose of the Study:
- To investigate the therapeutic efficacy of Methylene blue (MB) in rodent models of ischemic stroke.
- To explore the impact of MB administration timing on behavioral deficits, infarct volume, and white matter integrity.
- To elucidate the underlying mechanisms of MB's neuroprotective effects, focusing on white matter protection.
Main Methods:
- Utilized Middle Cerebral Artery Occlusion and reperfusion (MCAO) and photothrombotic MCAO (PT-MCAO) rodent models.
- Assessed behavioral deficits using the foot fault test and Garcia neurological score.
- Quantified infarct volume via TTC staining and evaluated white matter injury using black gold staining and Western blot for myelin basic protein (MBP).
Main Results:
- Intraperitoneal administration of MB, both immediately and 24 hours post-MCAO or PT-MCAO, significantly reduced infarct volume.
- MB treatment improved neurological deficit scores and mitigated white matter injury, evidenced by myelin basic protein (MBP) protection.
- These findings indicate MB's efficacy beyond the typical therapeutic time window.
Conclusions:
- Methylene blue (MB) demonstrates significant therapeutic potential for ischemic stroke, offering both neuroprotection and white matter protection.
- MB's ability to reduce white matter injury, in addition to neuronal protection, broadens its therapeutic applicability.
- MB administration is effective even when delayed up to 24 hours after ischemic events, highlighting its clinical relevance.
