Neuroprotective and Functional Improvement Effects of Methylene Blue in Global Cerebral Ischemia

Qing Lu, Donovan Tucker, Yan Dong, Ningjun Zhao, Quanguang Zhang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Transient global cerebral ischemia (GCI) causes delayed neuronal cell death in the vulnerable hippocampus CA1 subfield, as well as behavioral deficits. Ischemia reperfusion (I/R) produces excessive reactive oxygen species and plays a key role in brain injury. The mitochondrial electron respiratory chain is the main cellular source of free radical generation, and dysfunction of mitochondria has a significant impact on the neuronal cell death in ischemic brain. The aim of the present study is to investigate the potential beneficial effects of methylene blue (MB) in a four-vessel occlusion (4VO) GCI model on adult male rats. MB was delivered at a dose of 0.5 mg/kg/day for 7 days, through a mini-pump implanted subcutaneously after GCI. We first found that MB significantly improved ischemic neuronal survival in the hippocampal CA1 region as measured by cresyl violet staining as well as NeuN staining. We also found that MB has the ability to rescue ischemia-induced decreases of cytochrome c oxidase activity and ATP generation in the CA1 region following I/R. Further analysis with labeling of MitoTracker® Red revealed that the depolarization of mitochondrial membrane potential (MMP) was markedly attenuated following MB treatment. In addition, the induction of caspase-3, caspase-8, and caspase-9 activities and the increased numbers of TUNEL-positive cells of the CA1 region were significantly reduced by MB application. Correspondingly, Barnes maze tests showed that the deterioration of spatial learning and memory performance following GCI was significantly improved in the MB-treatment group compared to the ischemic control group. In summary, our study suggests that MB may be a promising therapeutic agent targeting neuronal cell death and cognitive deficits following transient global cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)5344-5355
Number of pages12
JournalMolecular Neurobiology
Volume53
Issue number8
DOIs
StatePublished - Oct 1 2016

Fingerprint

Methylene Blue
Brain Ischemia
Cell Death
Transient Ischemic Attack
Ischemia
Staining and Labeling
Hippocampal CA1 Region
Aptitude
Caspase 9
Caspase 8
Mitochondrial Membrane Potential
In Situ Nick-End Labeling
Electron Transport Complex IV
Electron Transport
Caspase 3
Brain Injuries
Reperfusion
Free Radicals
Reactive Oxygen Species
Hippocampus

Keywords

  • Functional improvement
  • Global cerebral ischemia
  • Methylene blue
  • Mitochondria
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Neuroprotective and Functional Improvement Effects of Methylene Blue in Global Cerebral Ischemia. / Lu, Qing; Tucker, Donovan; Dong, Yan; Zhao, Ningjun; Zhang, Quanguang.

In: Molecular Neurobiology, Vol. 53, No. 8, 01.10.2016, p. 5344-5355.

Research output: Contribution to journalArticle

Lu, Qing ; Tucker, Donovan ; Dong, Yan ; Zhao, Ningjun ; Zhang, Quanguang. / Neuroprotective and Functional Improvement Effects of Methylene Blue in Global Cerebral Ischemia. In: Molecular Neurobiology. 2016 ; Vol. 53, No. 8. pp. 5344-5355.
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