Combination Treatment with Methylene Blue and Hypothermia in Global Cerebral Ischemia

Lei Li, Rongli Yang, Pingjing Li, Hailong Lu, Jingbo Hao, Liyan Li, Donovan Tucker, Quanguang Zhang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Therapeutic hypothermia (TH) is the most potent therapeutic strategy for global cerebral ischemia (GCI), usually induced by cardiac arrest. TH has been shown both to suppress the delayed neuronal cell death in the vulnerable hippocampal CA1 subregion and to improve neurological outcomes in experimental animals after GCI. However, given the multiple adverse effects resulting from TH, application of such a therapy is typically limited. In recent years, methylene blue (MB) has emerged as a potential therapeutic drug for the treatment of neurodegenerative diseases. In this study, we investigated the beneficial effects of mild TH combined with MB treatment after GCI. We report that both the neuronal survival in the hippocampal CA1 region and the hippocampus-dependent spatial learning and memory in the combined treatment animals were enhanced compared to those in the single treatment animals. Mechanistic studies revealed that combined TH and MB treatment significantly attenuated mitochondrial dysfunction induced by GCI in the hippocampus CA1 region. The combined treatment also markedly suppressed GCI-induced reactive gliosis and inflammation and reduced oxidative stress while enhancing the antioxidant capacity of hippocampal CA1 neurons. Finally, combining TH and MB synergistically attenuated the intrinsic cytochrome c/caspase-3 apoptotic pathway induced by GCI. Our results suggest that TH and MB act synergistically to protect the ischemic brain and suppress cognitive impairment caused by GCI.

Original languageEnglish (US)
Pages (from-to)2042-2055
Number of pages14
JournalMolecular Neurobiology
Volume55
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Methylene Blue
Induced Hypothermia
Hypothermia
Brain Ischemia
Therapeutics
Hippocampus
Hippocampal CA1 Region
Induced Heart Arrest
Gliosis
Caspase 3
Neurodegenerative Diseases
Oxidative Stress
Cell Death
Antioxidants
Inflammation
Neurons
Brain

Keywords

  • Combination treatment
  • Global cerebral ischemia
  • Hypothermia
  • Learning and memory
  • Methylene blue
  • Neuroprotection

ASJC Scopus subject areas

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

Cite this

Combination Treatment with Methylene Blue and Hypothermia in Global Cerebral Ischemia. / Li, Lei; Yang, Rongli; Li, Pingjing; Lu, Hailong; Hao, Jingbo; Li, Liyan; Tucker, Donovan; Zhang, Quanguang.

In: Molecular Neurobiology, Vol. 55, No. 3, 01.03.2018, p. 2042-2055.

Research output: Contribution to journalArticle

Li, Lei ; Yang, Rongli ; Li, Pingjing ; Lu, Hailong ; Hao, Jingbo ; Li, Liyan ; Tucker, Donovan ; Zhang, Quanguang. / Combination Treatment with Methylene Blue and Hypothermia in Global Cerebral Ischemia. In: Molecular Neurobiology. 2018 ; Vol. 55, No. 3. pp. 2042-2055.
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