Ambroxol Improves Neuronal Survival and Reduces White Matter Damage through Suppressing Endoplasmic Reticulum Stress in Microglia after Intracerebral Hemorrhage.

Xuheng Jiang,Xiaofei Huang,Anyong Yu,Xiaojun Zhang,Jun Zhong,Bojin Kou,Chao Zhang,Ji Zhang,Fangke Xie,Quan Hu,Xuanyu Fang,Hongfei Ge

doi:10.1155/2020/8131286

Xuheng Jiang, Xiaofei Huang + Show 10 more

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https://doi.org/10.1155/2020/8131286

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Abstract

Intracerebral hemorrhage (ICH) has been becoming a serious public health problem. Pneumonia, occurring in 43% of all ICH patients, is a common complication heavily influencing outcome and accounting for more than 1/3 of the overall mortality in patients with ICH. Ambroxol may be an effective additional treatment for ICH patients with pneumonia. But its effect and potential mechanism on functional recovery post-ICH still remain elusive. In the present study, the results indicated that 35 mg/kg and 70 mg/kg ambroxol facilitated neuronal survival and reduced white matter fiber bundle damage due to mitigating microglial activation and reducing proinflammatory cytokine accumulation in mice with ICH. The possible mechanism might be due to suppressing endoplasmic reticulum stress involving the IRE1α/TRAF2 signaling pathway, which paves a new path for the treatment of ICH and opens a new window for the use of ambroxol in clinical practice.

Highlights

Intracerebral hemorrhage (ICH) has been becoming a serious public health problem, which accounts for 10–20% of all strokes worldwide and is associated with high rates of death and disability [1, 2]
The results showed that 35 mg/kg and 70 mg/kg ambroxol facilitated functional recovery using the rotarod test and adhesive removal test from day 3 to 14, compared with that in the ICH group (Figures 2(a) and 2(b))
To reveal the reason why ambroxol enhances functional recovery, the brain water content on day 3 was assessed, and the results demonstrated that group of 35 mg/kg and 70 mg/kg ambroxol significantly reduced brain water content, compared with that in the ICH group (Figure 2(c))

Summary

Introduction

Intracerebral hemorrhage (ICH) has been becoming a serious public health problem, which accounts for 10–20% of all strokes worldwide and is associated with high rates of death and disability [1, 2]. Except for antibiotic treatment, ambroxol has been proven to be an effective airway humidification liquid, which improves the patient’s lung function through promoting the synthesis and secretion of pulmonary surfactant and diluting sputum to facilitate pulmonary ventilation dysfunction, thereafter, inhibiting further pulmonary damage after severe brain injury [5]. Ambroxol was usually employed to protect lung against infection after ICH. A recent investigation has shown that ambroxol facilitates and protects motor units, improves axonal plasticity, and extends overall survival via inhibiting nonlysosomal (GBA2) glucocerebrosidase activity in the spinal cord with amyotrophic lateral sclerosis (ALS) in the SOD1G86R mice [9]. The effect of ambroxol on brain recovery and potential mechanism still remains elusive

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