PROTECTIVE EFFECT OF STOBADINE, A PYRIDOINDOLE ANTIOXIDANT, IN HYPOXIA-REOXYGENATION INJURY OF GANGLIONIC AND HIPPOCAMPAL NEUROTRANSMISSION

Hypoxia (HYP) followed by reoxygenation (REOX) occurs frequently in th e pathophysiology of the CNS. Free oxygen radicals (FOR) may participa te in cerebral injury under such circumstances. Pharmacological contro l of the generation and/or subsequent effects of FOR by new effective compounds might contribute to the treatment of disorders such as strok e and cerebral trauma. Effects of stobadine, a pyridoindole antioxidan t that is able to interact with some FOR, were analyzed on synaptic tr ansmission in rat superior cervical ganglia and hippocampal slices dur ing HYP-REOX procedure in vitro. The amplitude of compound action pote ntial in the ganglion evoked by supramaximal electrical stimulation of preganglionic nerve was reduced to approximately 20% of the control v alue during HYP (90 min). The action potential did not recover during REOX (60 min). Stobadine (10 mM) applied before, during, and after HYP , did not change the HYP-induced inhibition; however, a significant re covery of transmission (to 78.5% +/- 8.3) occurred during REOX. A simi lar effect was observed in the presence of the antioxidant Trolox (0.2 mM), a derivative of alpha-tocopherol. Stobadine, in concentrations o f > 30 mu M inhibited ganglionic transmission in a concentration-depen dent manner. HYP lasting more than 2-3 min fully depressed field actio n potentials evoked in hippocampal CA1 region neurons by supramaximal electrical stimulation of Schaffer collaterals. If HYP exceeded 8 min, transmission did not recover during REOX. Stobadine (10 mu M) applied during HYP significantly enhanced the probability of transmission rec overy in the REOX period. Some preparations recovered following HYP la sting as long as 13-15 min. On applying the compound before, during, a nd after HYP that lasted for 8 min, the transmission recovery was 72.6 % +/- 21.8 of the control value, compared to only 16.1% +/- 12.7 in th e untreated preparations. In concentrations ranging from 0.3-1.73 mM, stobadine inhibited hippocampal transmission. Stobadine proved to be a n effective agent in the protection of synaptic transmission against H YP-REOX-induced injury in both neuronal preparations studied in vitro. This effect might be linked to the antioxidant and free radical scave nging effects of stobadine.