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Brain and Nerve No to Shinkei Volume 45, Issue 4 （April 1993）

Brain and Nerve 脳と神経 45巻4号（1993年4月発行）

Japanese English

原著

セレブロライジン（FPF 1070）による海馬遅発性細胞壊死の防御と・OHラジカルの関与 Protective Effect of FPF 1070 (Cerebrolysin) on Delayed Neuronal Death in the Gerbil: Detection of Hydroxyl Radicals with Salicylic Acid 杉田之宏 ¹ , 近藤智善 ² , 金澤章 ² , 伊藤敬 ² , 水野美邦 ² Yukihiro Sugita ¹ , Tomoyoshi Kondo ² , Akira Kanazawa ² , Takashi Itou ² , Yoshikuni Mizuno ² ¹国立精神・神経センター国府台病院神経内科 ²順天堂大学医学部脳神経内科 ¹Department of Neurology, National Center of Neurology and Psychiatry Kohnodai Hospital ²Department of Neurology, Juntendo University School of Medicine キーワード： delayed neuronal death , FPF 1070 , salicylate , hydroxyl radical , dimethylsulfoxide Keyword: delayed neuronal death , FPF 1070 , salicylate , hydroxyl radical , dimethylsulfoxide pp.325-331

発行日 1993年4月1日 Published Date 1993/4/1

DOI https://doi.org/10.11477/mf.1406900465

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Abstract 文献概要
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　NGF様作用をもつセレブロライジンの遅発性細胞壊死に対する防御効果を検討した。セレブロライジンの作用機序を検討するにあたりフリーラジカルの関与を考慮し，虚血・血流再開時の・OHの発生と，それに対するセレブロライジンの影響について検索した。サリチル酸と・OHの反応生成物である2, 3—DHBA，2, 5—DHBAの測定により・OHの計測を行った。セレブロライジンの虚血2時間前投与により遅発性細胞壊死に対する防御効果が認められた。また，虚血・血流再開時の・OHの大量発生と，セレブロライジンによる消去が認められ，遅発性細胞壊死防御の機序の1つとして虚血・血流再開時の・OH発生の消去が関連している可能性が示唆された。

Cerebrolysin (FPF1070) is an extract from pig brain obtained after enzymic digestion, containing free amino acids (85%) and low-molecular weight amino acid sequences (15%).

We studied FPF 1070 to determine its ability to protect against delayed neuronal death in the gerbil when administered before and after ischemia. Tran-sient forebrain ischemia was produced by occluding both common carotid arteries. Morphological changes in the CA1 sector of thhe hippocampus were evaluated 4 days after 5min. occlusion. The formation of hydroxyl radicals in the postischemic (15min. occlusion) reperfused (2min.) brain was measured with HPLC using salicylate (SA). SA reacts with hydroxyl radicals and yields 2, 3- and 2, 5-dihydroxybenzoic acid (2,3- and 2,5-DHBA), which can be detected by HPLC-ECD.

Gerbils treated with FPF 1070 revealed significant protection of CA1 neurons when it was applied 2hrs before the occlusion. In contrast, no clear beneficial effects were observed when FPF 1070 was adminis-tered immediately after the recirculation.

Concentrations of 2, 3- and 2, 5-DHBA after reperfusion increased significantly compared to the basal levels both in the hippocampus and cerebral cortex. The 2, 5-DHBA contents in the postischemic reperfused brain was significantly reduced when FPF 1070 was administered 2hr. before the occlu-sion.

The administration of dimethylsulfoxide (DMSO) , a hydroxyl radical scavenger, prevented ischemia - reperfusion - induced delayed neuronal death, and significantly reduced the 2, 5-DHBA content after reperfusion.

The results indicated that hydroxyl radicals are produced in the postischemic-reperfused brain and that hydroxyl radical scavenging action of FPF 1070 played an important role in preventing delayed neuronal death.