The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization
| Autor: | Orsolya Tóth, Ibolya Horváth, Ákos Menyhárt, Dániel Varga, Ferenc Bari, Rita Frank, Írisz Szabó, Dóra Hantosi, Zsolt Török, Ákos Hunya, László Vígh, Eszter Farkas |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Dihydropyridines Stimulation Rats Sprague-Dawley 03 medical and health sciences Hyperaemia 0302 clinical medicine Internal medicine medicine Animals Nimodipine Pharmacology business.industry Calcium channel Dihydropyridine Somatosensory Cortex Calcium Channel Blockers Research Papers Rats Electrophysiology 030104 developmental biology medicine.anatomical_structure Cerebral blood flow Cerebral cortex Cerebrovascular Circulation Cardiology medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Br J Pharmacol |
| ISSN: | 1476-5381 |
| Popis: | Background and purpose A new class of dihydropyridine derivatives, which act as co-inducers of heat shock protein but are devoid of calcium channel antagonist and vasodilator effects, has recently been developed with the purpose of selectively targeting neurodegeneration. Here, we evaluated the action of one of these novel compounds LA1011 on neurovascular coupling in the ischaemic rat cerebral cortex. As a reference, we applied nimodipine, a vasodilator dihydropyridine and well-known calcium channel antagonist. Experimental approach Rats were treated with LA1011 or nimodipine, either by chronic, systemic (LA1011), or acute, local administration (LA1011 and nimodipine). In the latter treatment group, global forebrain ischaemia was induced in half of the animals by bilateral common carotid artery occlusion under isoflurane anaesthesia. Functional hyperaemia in the somatosensory cortex was created by mechanical stimulation of the contralateral whisker pad under α-chloralose anaesthesia. 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. Key results 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 hyperaemia in response to both somatosensory stimulation and SD, particularly under ischaemia. Conclusions and implications In contrast to the CBF improvement achieved with nimodipine, LA1011 seems not to have discernible cerebrovascular effects but may up-regulate the stress response. |
| Databáze: | OpenAIRE |
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