Hongping Miao1, Yongxiang Jiang2, Junjun Geng1, Bo Zhang1, Gang Zhu3, Jun Tang4. 1. Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. 2. Department of Neurosurgery, The second affiliated hospital of Chongqing Medical University, Chongqing, China. 3. Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: gangzhu6666@sina.com. 4. Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: tangjun@tmmu.edu.cn.
Abstract
OBJECTIVES: Intracerebral hemorrhage (ICH) is one of the leading causes of disability and mortality in adult, which lacks effective therapies. Edaravone has showed its neuroprotective effects after ischemia stroke, but its effects and possible mechanisms after ICH are poorly understood. Here, we investigated whether edaravone confers neuroprotection after ICH in rats and explored the potential mechanisms involved. METHODS: ICH was induced in the right basal ganglia of Sprague-Dawley rats by stereotacticly injection of 200 μl autologous blood. Edaravone (3 mg/kg) or vehicle (saline) was administered intravenously and NLRP3 selective antagonist (MCC950, 10 mg/kg) was intraperitoneally injected to study the potential mechanism. Water Morris Maze Test and Rotarod test were used to elucidate neurological function and Fluoro-Jade C was used to study neurodegeneration after ICH. Western blot assay, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry were used to check the expression of molecules involved. RESULTS: As a result, we found that edaravone significantly alleviated brain edema and conferred the neurological deficits of rats after ICH. Hematoma increased NLRP3 expression in microglia, which was decreased by edaravone. Moreover, we demonstrated that edaravone shared a similar effect with MCC950 on alleviating neurodegeneration and decreasing the expression of IL-1β, Caspase 1 and NF-κB in protein or mRNA. Lastly, edaravone and MCC950 both increased the number of Tuj-1 positive neuronal cells peripheral hematoma. CONCLUSIONS: The present study demonstrated that edaravone conducted neuroprotection after ICH partially via suppressing NF-κB-dependent NLRP3 in microglia, which contributed a novel evidence for clinic usage of edaravone after ICH.
OBJECTIVES:Intracerebral hemorrhage (ICH) is one of the leading causes of disability and mortality in adult, which lacks effective therapies. Edaravone has showed its neuroprotective effects after ischemia stroke, but its effects and possible mechanisms after ICH are poorly understood. Here, we investigated whether edaravone confers neuroprotection after ICH in rats and explored the potential mechanisms involved. METHODS:ICH was induced in the right basal ganglia of Sprague-Dawley rats by stereotacticly injection of 200 μl autologous blood. Edaravone (3 mg/kg) or vehicle (saline) was administered intravenously and NLRP3 selective antagonist (MCC950, 10 mg/kg) was intraperitoneally injected to study the potential mechanism. Water Morris Maze Test and Rotarod test were used to elucidate neurological function and Fluoro-Jade C was used to study neurodegeneration after ICH. Western blot assay, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry were used to check the expression of molecules involved. RESULTS: As a result, we found that edaravone significantly alleviated brain edema and conferred the neurological deficits of rats after ICH. Hematoma increased NLRP3 expression in microglia, which was decreased by edaravone. Moreover, we demonstrated that edaravone shared a similar effect with MCC950 on alleviating neurodegeneration and decreasing the expression of IL-1β, Caspase 1 and NF-κB in protein or mRNA. Lastly, edaravone and MCC950 both increased the number of Tuj-1 positive neuronal cells peripheral hematoma. CONCLUSIONS: The present study demonstrated that edaravone conducted neuroprotection after ICH partially via suppressing NF-κB-dependent NLRP3 in microglia, which contributed a novel evidence for clinic usage of edaravone after ICH.
Authors: Kathryn N Kearns; Natasha Ironside; Min S Park; Bradford B Worrall; Andrew M Southerland; Ching-Jen Chen; Dale Ding Journal: Neurocrit Care Date: 2021-08-02 Impact factor: 3.210