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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.01133

Methylene blue reduces neuronal apoptosis and improves blood-brain barrier integrity after traumatic brain injury

 Jun Shen1, Wenqiang Xin1, Qifeng LI1,  YaLong Gao1,  Lili Yuan2* and  Jianning Zhang1*
  • 1Department of Neurosurgery, Tianjin Medical University General Hospital, China
  • 2Department of Neurology, First Affiliated Hospital of Wannan Medical College, China

Objective: To investigate whether Methylene blue (MB) treatment can reverse neuronal mitochondrial dysfunction caused by Oxygen Glucose Deprivation /reoxygenation (OGD) injury and then investigate whether MB treatment can reduce neuronal apoptosis and improve blood-brain barrier (BBB) integrity in TBI animals.
Methods: Reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) were used to evaluate mitochondrial function. The Terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess neuronal apoptosis in vitro. TUNEL and immunofluorescence staining for neuronal nuclei (NeuN) were combined to assess neuronal apoptosis in vivo. An evans blue (EB) permeability assay and brain water content (BWC) were used to measure BBB permeability in vivo. The Morris water maze (MWM), rotarod test, and modified Neurological Severity Score (mNSS) test were employed to assess the prognosis of TBI mice.
Results: MB treatment significantly reversed neuronal mitochondrial dysfunction caused by OGD injury. Both in vitro and in vivo, MB treatment reduced neuronal apoptosis and improved BBB integrity. In TBI animals, treatment with MB not only improved cognitive and motor function caused by TBI but also significantly improved overall neurological function.
Conclusions: Our findings suggest that MB is a potential candidate for the treatment of TBI. Future research should focus on other therapeutic effects and mechanisms of MB in secondary brain injury.

Keywords: Keyword: Adenosine triphosphate, Apoptosis, Blood-Brain Barrier, Methylene Blue, Reactive Oxygen Species, Traumatic Brain Injury

Received: 05 Aug 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Shen, Xin, LI, Gao, Yuan and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Lili Yuan, Department of Neurology, First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui Province, China, molly8338@126.com
Mx. Jianning Zhang, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China, jianningzhang@hotmail.com