Nimodipine accelerates the restoration of functional hyperemia during spreading oligemia

Ákos Menyhárt; Armand Rafael Bálint; Péter Kozák; Ferenc Bari; Eszter Farkas

doi:10.1111/jnc.15792

Nimodipine accelerates the restoration of functional hyperemia during spreading oligemia

J Neurochem. 2023 Feb 22. doi: 10.1111/jnc.15792. Online ahead of print.

Authors

Ákos Menyhárt^{1

2}, Armand Rafael Bálint^{2

3}, Péter Kozák², Ferenc Bari³, Eszter Farkas^{1

2}

Affiliations

¹ Hungarian Centre of Excellence for Molecular Medicine-University of Szeged, Cerebral Blood Flow and Metabolism Research Group, Szeged, Hungary.
² Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
³ Department of Medical Physics and Informatics, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.

PMID: 36810711
DOI: 10.1111/jnc.15792

Abstract

Spreading depolarization (SD) is assumed to be the pathophysiological correlate of migraine aura, leading to spreading depression of activity and a long-lasting vasoconstriction known as spreading oligemia. Furthermore, cerebrovascular reactivity is reversibly impaired after SD. Here, we explored the progressive restoration of impaired neurovascular coupling to somatosensory activation during spreading oligemia. Also, we evaluated whether nimodipine treatment accelerated the recovery of impaired neurovascular coupling after SD. Male, 4-9-month-old C57BL/6 mice (n = 11) were anesthetized with isoflurane (1%-1.5%), and SD was triggered with KCl through a burr hole made at the caudal parietal bone. EEG and cerebral blood flow (CBF) were recorded minimally invasively with a silver ball electrode and transcranial laser-Doppler flowmetry, rostral to SD elicitation. The L-type voltage-gated Ca²⁺ channel blocker nimodipine was administered i.p. (10 mg/kg). Whisker stimulation-related evoked potentials (EVPs) and functional hyperemia were assessed under isoflurane (0.1%)-medetomidine (0.1 mg/kg i.p.) anesthesia before, and repeatedly after SD, at 15-min intervals for 75 minutes. Nimodipine accelerated the recovery of CBF from spreading oligemia (time to full recovery, 52 ± 13 vs. 70 ± 8 min, nimodipine vs. control) and exhibited a tendency to shorten the duration of the SD-related EGG depression duration. The amplitudes of EVP and functional hyperemia were markedly reduced after SD, and progressively recovered over an hour post-SD. Nimodipine exerted no impact on EVP amplitude but consistently increased the absolute level of functional hyperemia from 20 min post-CSD (93 ± 11% vs. 66 ± 13%, nimodipine vs. control). A linear, positive correlation between EVP and functional hyperemia amplitude was skewed by nimodipine. In conclusion, nimodipine facilitated CBF restoration from spreading oligemia and the recovery of functional hyperemia post-SD, which were linked to a tendency of an accelerated return of spontaneous neural activity after SD. The use of nimodipine in migraine prophylaxis is suggested to be re-visited.

Keywords: cerebral blood flow; migraine with aura; neurovascular coupling; nimodipine; spreading depolarization; spreading oligemia.

Abstract

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