グルタミン酸抗体と細胞外酸性の神経保護効果
D A Kaku1, R G Giffard, D W Choi
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.
まとめ
細胞外酸性は,ニューロンを酸素欠乏から保護し,グルタミン酸対抗剤の神経保護効果を高めます. この組み合わせは,長期にわたる低酸素状態下でも,重要なニューロン生存率を提供します.
科学分野:
- 神経科学は神経科学である.
- 細胞生物学 細胞生物学
- 病理生理学 病理生理学とは
背景:
- グルタミン酸逆抗剤は,体内および体外において,低毒性損傷に対する神経保護効果を示します.
- 以前のインビトロ研究では,インビボ低酸素症-低血圧症の特徴である酸性状態が再現されていなかった.
研究 の 目的:
- 細胞外酸性およびグルタミン酸対抗剤の神経保護効果を,in vivoの低酸素性-低血症を模倣する条件下で調査する.
- 細胞外酸度が,グルタミン酸受容体アンタゴニストが神経細胞を保護する効果を高めるかどうかを判断する.
主な方法:
- ネズミの皮質培養は,酸素とグルコースの欠乏にさらされた.
- 細胞外酸性単独およびN-メチル-D-アスパルテート (NMDA) とアルファ-アミノ-3-ヒドロキシ-5-メチル-4-イソクサゾロプロピオネート (AMPA) -カイネート抗体との組み合わせによるニューロン死亡に対する効果を評価した.
主要な成果:
- 細胞外酸性だけでは,酸素とグルコースの欠乏の間に神経細胞死亡を減少させました.
- 細胞外酸性およびグルタミン酸対抗薬 (NMDAおよびAMPA-カイナート) の組み合わせは,神経細胞死亡を著しく減少させました.
- 組み合わせたアプローチで治療されたニューロンは,長時間酸素とグルコースの欠乏を許容し,アストロサイトと比較できる生存率を示しました.
結論:
- 細胞外酸性は,イオノトロプ的グルタミン酸受容体活性化の単なる衰弱を超えて神経保護を提供します.
- 細胞外酸性およびグルタミン酸対抗剤の組み合わせは,グルタミン酸対抗剤単独と比較して優れた神経保護を提供します.
- これらの発見は,ヒポキシア・イシュケミアを含む状態のための潜在的な治療戦略を示唆しています.
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