Efficacy of cerebroprotective substances in the management of functional disorders induced by the cytotoxic brain oedema-producing substance hexachlorophene

Abstract

The hexachlorophene-induced cytotoxic brain oedema is used as experimental model of brain damage, suitable for testing cerebroprotective substances. It has clinical importance since many brain injuries are accompanied by an oedema. The primary target of the neurotoxin, hexachlorophene, is the neuronal cell membrane, but it also causes secondary effects including a disruption of myelin lamellae, increases in water and sodium content, decreases of potassium content, and vacuolation in the white matter. Rats received orally hexachlorophene 240 mg/kg a day for three weeks by liquid diet. The disruption of coordinative motor response, observed in a specially developed test, was used to characterise hexachlorophene-induced injuries in studies designed to evaluate the potential of cerebroprotective substances. Because of their membranotropic efficacy some nootropic substances with different modes of action were examined. The disturbance of coordinative motor response was restored significantly earlier than in spontaneous remission following administration of piracetam, pyritinol, methyl glucamine orotate, naftidrofuryl, and also under the influence of the calcium antagonists cinnarizine, flunarizine and nifedipine. These results support the therapeutic use of nootropic substances in the management of neurotoxic injuries and brain oedema.