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The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization

Szabó, Írisz and M.Tóth, Orsolya and Török, Zsolt and Varga, Dániel Péter and Menyhárt, Ákos and Hunya, Ákos and Bari, Ferenc and Horváth, Ibolya and Vigh, László and Farkas, Eszter (2019) The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization. BRITISH JOURNAL OF PHARMACOLOGY, 176 (9). pp. 1222-1234. ISSN 0007-1188

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Abstract

A new class of heat shock protein co-inducer dihydropyridine derivatives devoid of calcium channel antagonist and vasodilator effects have been recently developed with the purpose to target neurodegeneration selectively. Here we set out to evaluate the action of one of these novel compounds LA1011 on neurovascular coupling in the ischemic rat cerebral cortex. As a reference, we applied nimodipine, a well-known calcium channel antagonist, vasodilator dihydropyridine compound.Rats (n=62) were treated with LA1011 or nimodipine, either by chronic, systemic (LA1011, 1 mg/kg b.w.), or acute, local administration (LA1011 and nimodipine, 100 μM). In the latter treatment group, global forebrain ischemia was induced in half of the animals by bilateral common carotid artery occlusion under isoflurane anesthesia. Functional hyperemia in the somatosensory cortex was created by mechanical stimulation of the contralateral whisker pad under alpha-chloralose anesthesia. Spreading depolarization (SD) events were elicited subsequently by 1 M KCl. Local field potential and cerebral blood flow (CBF) in the parietal somatosensory cortex were monitored by electrophysiology and laser Doppler flowmetry.LA1011 did not alter CBF, but intensified SD, presumably indicating the co-induction of heat shock proteins, and, perhaps an anti-inflammatory effect. Nimodipine attenuated evoked potentials and SD. In addition to the elevation of baseline CBF, nimodipine augmented hyperemia in response to both somatosensory stimulation and SD, particularly under ischemia. In conclusion, in contrast with CBF improvement achieved by nimodipine, LA1011 seems not to have discernible cerebrovascular effects, but may upregulate stress response.

Item Type: Article
Subjects: R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 23 Nov 2019 13:05
Last Modified: 23 Nov 2019 13:05
URI: http://real.mtak.hu/id/eprint/103675

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