Edaravone Administration Confers Neuroprotection after Experimental Intracerebral Hemorrhage in Rats via NLRP3 Suppression.

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.

• Authors: Hongping Miao, Yongxiang Jiang, Junjun Geng, Bo Zhang, Gang Zhu, Jun Tang
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 29 Issue 1 Pg. 104468 (Jan 2020) ISSN: 1532-8511 [Electronic] United States
• PMID: 31694784 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• IL1B protein, rat
• Inflammasomes
• Interleukin-1beta
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents
• Nlrp3 protein, rat
• Caspase 1
• Edaravone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Behavior, Animal (drug effects)
• Brain (drug effects, metabolism, pathology, physiopathology)
• Caspase 1 (metabolism)
• Cerebral Hemorrhage (drug therapy, metabolism, pathology, physiopathology)
• Disease Models, Animal
• Down-Regulation
• Edaravone (pharmacology)
• Inflammasomes (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Maze Learning (drug effects)
• Microglia (drug effects, metabolism, pathology)
• Motor Activity (drug effects)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neuroprotective Agents (pharmacology)
• Rats, Sprague-Dawley
• Signal Transduction