NMDA attenuates the neurovascular response to hypercapnia in the neonatal cerebral cortex

Cortical spreading depolarization (SD) involves activation of NMDA receptors and elicit neurovascular unit dysfunction. NMDA cannot trigger SD in newborns, thus its effect on neurovascular function is not confounded by other aspects of SD. The present study investigated if NMDA affected hypercapnia-...

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Bibliographic Details
Main Authors: Remzső Gábor
Németh János
Tóth-Szűki Valéria
Varga Viktória Éva
Kovács Viktória
Domoki Ferenc
Format: Article
Published: 2019
Series:SCIENTIFIC REPORTS 9
doi:10.1038/s41598-019-55468-1

mtmt:31053400
Online Access:http://publicatio.bibl.u-szeged.hu/18005
Description
Summary:Cortical spreading depolarization (SD) involves activation of NMDA receptors and elicit neurovascular unit dysfunction. NMDA cannot trigger SD in newborns, thus its effect on neurovascular function is not confounded by other aspects of SD. The present study investigated if NMDA affected hypercapnia-induced microvascular and electrophysiological responses in the cerebral cortex of newborn pigs. Anesthetized piglets were fitted with cranial windows over the parietal cortex to study hemodynamic and electrophysiological responses to graded hypercapnia before/after topically applied NMDA assessed with laser-speckle contrast imaging and recording of local field potentials (LFP)/neuronal firing, respectively. NMDA increased cortical blood flow (CoBF), suppressed LFP power in most frequency bands but evoked a 2.5 Hz delta oscillation. The CoBF response to hypercapnia was abolished after NMDA and the hypercapnia-induced biphasic changes in delta and theta LFP power were also altered. MK-801 prevented NMDA-induced increases in CoBF and the attenuation of microvascular reactivity to hypercapnia. The neuronal nitric oxide synthase (nNOS) inhibitor (N-(4 S)-4-amino-5-[aminoethyl] aminopentyl-N'-nitroguanidin) also significantly preserved the CoBF response to hypercapnia after NMDA, although it didn't reduce NMDA-induced increases in CoBF. In conclusion, excess activation of NMDA receptors alone can elicit SD-like neurovascular unit dysfunction involving nNOS activity.
Physical Description:Paper 18900-13 p
ISSN:2045-2322