[Protective effect of FPF 1070 (cerebrolysin) on delayed neuronal death in the gerbil--detection of hydroxyl radicals with salicylic acid]

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. Transient forebrain ischemia was produced by occluding both common carotid arteries. Morphological changes in the CA1 sector of the hippocampus were evaluated 4 days after 5 min. occlusion. The formation of hydroxyl radicals in the postischemic (15 min. occlusion) reperfused (2 min.) 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 2 hrs before the occlusion. In contrast, no clear beneficial effects were observed when FPF 1070 was administered 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 2 hr. before the occlusion. 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.