Abstract
IntroductionIschemic stroke is a global burden that contributes to the disability and mortality of millions of patients. This study aimed to evaluate the efficacy of combined MB (methylene blue) and NBO (normobaric hyperoxia) therapy in experimental ischemic stroke.MethodsRats with transient (60 min) MCAO (middle cerebral artery occlusion) were treated with: (1) air + vehicle (N = 8), (2) air + MB (N = 8), (3) NBO + vehicle (N = 7), and (4) NBO + MB (N = 9). MB (1 mg/kg) was administered at 30 min, again on days 2, 7, and 14 after stroke. NBO was given during MRI (30–150 min) on day 0, and again 1 h each during MRI on subsequent days. Serial diffusion, perfusion and T2 MRI were performed to evaluate lesion volumes. Foot‐fault and cylinder tests were performed to evaluate sensorimotor function.ResultsThe major findings were: (1) NBO + MB therapy showed a greater decrease in infarct volume compared to NBO alone, but similar infarct volume compared to MB alone, (2) NBO + MB therapy accelerated sensorimotor functional recovery compared to NBO or MB alone, (3) Infarct volumes on day 2 did not change significantly from those on day 28 for all four groups, but behavioral function continued to show improved recovery in the NBO + MB group.ConclusionsThese findings support the hypothesis that combined NBO + MB further improves functional outcome and reduces infarct volume compared to either treatment alone and these improvements extended up to 28 days.
Highlights
Ischemic stroke is a global burden that contributes to the disability and mortality of millions of patients
Arterial oxygen saturation increased in the hyperoxia groups NBO + Vehicle and NBO + MB as expected
Abnormal CBF was detected at 30 min after MCAO, and were not statistically different amongs all four groups at 30 min
Summary
Ischemic stroke is a global burden that contributes to the disability and mortality of millions of patients. This study aimed to evaluate the efficacy of combined MB (methylene blue) and NBO (normobaric hyperoxia) therapy in experimental ischemic stroke. Conclusions: These findings support the hypothesis that combined NBO + MB further improves functional outcome and reduces infarct volume compared to either treatment alone and these improvements extended up to 28 days. MB-mediated neuroprotection has been linked to enhanced autophagy (Jiang et al 2015), inhibited apoptosis in the ischemic tissue (Jiang et al 2015), and augmented mitophagy (Di et al 2015). These positive neuroprotective a 2016 The Authors.
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