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Ischaemia triggered by spreading neuronal activation is inhibited by vasodilators in rats
Author(s) -
Dreier Jens P.,
Petzold Gabor,
Tille Katrin,
Lindauer Ute,
Arnold Guy,
Heinemann Uwe,
Einhäupl Karl M.,
Dirnagl Ulrich
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0515i.x
Subject(s) - cortical spreading depression , vasodilation , hyperaemia , chemistry , vasoconstriction , perfusion , nitric oxide synthase , biophysics , medicine , snap , endocrinology , nitric oxide , neuroscience , anesthesia , biology , blood flow , organic chemistry , migraine , computer graphics (images) , computer science
1 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). 2 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. 3 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. 4 Co‐application of a NO. 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. 5 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. 6 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.