Ischaemia triggered by spreading neuronal activation is inhibited by vasodilators in rats.
It has been previously shown that spreading neuronal activation can generate a cortical spreading ischaemia (CSI) in rats. The purpose of the present study was to investigate whether vasodilators cause CSI to revert to a normal cortical spreading depression (CSD).A KCl-induced CSD travelled from an open cranial window to a closed window where the cortex was superfused with physiological artificial cerebrospinal fluid (ACSF). At the closed window, recordings revealed a short-lasting negative slow potential shift accompanied by a variable, small and short initial hypoperfusion followed by hyperaemia and then oligaemia. In contrast, spreading neuronal activation locally induced CSI at the closed window when ACSF contained a NO. synthase (NOS) inhibitor, N(G)-nitro-L-arginine, and an increased K+ concentration ([K+]ACSF). CSI was characterised by a sharp and prolonged initial cerebral blood flow decrease to 29 +/- 11 % of the baseline and a prolonged negative potential shift. Co-application of a NOá donor, S-nitroso-N-acetylpenicillamine, and NOS inhibitor with high [K+]ACSF re-established a short-lasting negative potential shift and spreading hyperaemia typical of CSD. Similarly, the NO.-independent vasodilator papaverine caused CSI to revert to a pattern characteristic of CSD. In acute rat brain slices, NOS inhibition and high [K+]ACSF did not prolong the negative slow potential shift compared to that induced by high [K+]ACSF alone. The data indicate that the delayed recovery of the slow potential was caused by vasoconstriction during application of high [K+]ACSF and a NOS inhibitor in vivo. This supports the possibility of a vicious circle: spreading neuronal activation induces vasoconstriction, and vasoconstriction prevents repolarisation during CSI. Speculatively, this pathogenetic process could be involved in migraine-induced stroke.
Dreier
J P
JP
Department of Experimental Neurology, Humboldt-University, Berlin, Germany. jens.dreier@charite.de
Petzold
G
G
Tille
K
K
Lindauer
U
U
Arnold
G
G
Heinemann
U
U
Einhäupl
K M
KM
Dirnagl
U
U
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000502:physiology*; D004338:Drug Combinations; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology; D066298:In Vitro Techniques; D007511:Ischemia / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009994:Osmolar Concentration; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D010208:Papaverine; D011188:Potassium