Ischaemia triggered by spreading neuronal activation is inhibited by vasodilators in rats

1. It has been previously shown that spreading neuronal activation can gene rate a cortical spreading ischaemia (CSI) in rats. The purpose of the prese nt study was to investigate whether vasodilators cause CSI to revert to a n ormal cortical spreading depression (CSD). 2. A KCl-induced CSD travelled from an open cranial window to a closed wind ow where the cortex was superfused with physiological artificial cerebrospi nal fluid (ACSF). Bt the closed window, recordings revealed a short-lasting negative slow potential shift accompanied by a variable, small and short i nitial hypoperfusion followed by hyperaemia and then oligaemia. 3. In contrast, spreading neuronal activation locally induced CSI at the cl osed window when ACSF contained a NO synthase (NOS) inhibitor, N-G-nitro-L- arginine, and an increased K+ concentration ([K+](ACSF)). CSI was character ised by a sharp and prolonged initial cerebral blood flow decrease to 29 +/ - 11 % of the baseline and a prolonged negative potential shift. 4. Go-application of a NO donor, S-nitroso-N-acetylpenicillamine, and NOS i nhibitor with high [K+](ACSF) re-established a short-lasting negative poten tial shift and spreading hyperaemia typical of CSD. Similarly, the NO-indep endent vasodilator papaverine caused CSI to revert to a pattern characteris tic of CSD. 5. In acute rat brain slices, NOS inhibition and high [K+](ACSF) did not pr olong the negative slow potential shift compared to that induced by high [K +](ACSF) alone. 6. The data indicate that the delayed recovery of the slow potential was ca used by vasoconstriction during application of high [K+](ACSF) and a NOS in hibitor in vivo. This supports the possibility of a vicious circle: spreadi ng neuronal activation induces vasoconstriction, and vasoconstriction preve nts repolarisation during CSI. Speculatively, this pathogenetic process cou ld be involved in migraine-induced stroke.