ENDOTHELIN-1 EXACERBATES FOCAL CEREBRAL-ISCHEMIA WITHOUT EXERTING NEUROTOXIC ACTION IN-VITRO

In a model of focal cerebral ischemia in mice, intracisternal injectio n of 5 and 10 pmol/mouse endothelin-1 significantly increased the infa rcted surface area by 15.5% and by 23.5%, respectively. Endothelin-1 ( 0.01, 1, and 100 nmol/l) added to the primary neuronal cultures of chi ck embryo cerebral hemispheres for 1 h and 24 h did not influence the viability of the neurons or the protein content of the cultures. When applied simultaneously with 1 mmol/I sodium cyanide for 30 min, endoth elin-I (0.01, 1, and 100 nM) did not modify the hypoxia-induced change s. The results show that exogenously applied endothelin-1 could exacer bate cerebral ischemia, probably due to its vasoconstrictive propertie s and not to a direct neurotoxic effect.