ePoster

Ketamine prevents the inverse haemodynamic response to spreading depolarization in ischaemic cortical tissue

Robert C Wykes, Samuel Flaherty, Edu Masvidal-Codina, Anton Guimera-Brunet
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Robert C Wykes, Samuel Flaherty, Edu Masvidal-Codina, Anton Guimera-Brunet

Abstract

Spreading Depolarizations (SDs) are electrographic events that arise post-stroke and correlate with worsening outcome. The haemodynamic response to SD is vasodilation in well perfused tissue. However, SDs induce hypoperfusion in ischemic tissue, further decreasing the viability of ‘at risk’ tissue.Traditional metal-based electrodes are limited in their ability to faithfully record DC-coupled potential shifts including SD. In contrast, Graphene micro-transistor arrays (gSGFETs) precisely record SDs without signal attenuation, distortion or voltage drift; and their transparency allows simultaneous blood flow imaging.We applied multichannel gSGFETs to investigate bidirectional interactions between SDs and regional blood flow. Photothrombosis or distal middle cerebral artery occlusion resultant from topical application of ferric chloride were used to induce cortical ischaemia.In both models a positive correlation between SD duration and localised perfusion deficit was observed. Where perfusion deficit was 35% lower than baseline values the haemodynamic response to SD was predominately vasoconstrictive. In mildly ischaemic tissue SD’s induced a biphasic haemodynamic response (vasoconstriction followed by vasodilation), and in relatively uncompromised tissued only vasodilation in response to an SD was observed. Thus gSGFET arrays can be used to map the continuum of SD-induced haemodynamic responses in real-time.In ischaemic tissue, administration of ketamine narrowed the waveform of subsequent SD’s, converting SD-induced hypoperfusion within ‘at risk’ tissue to a transient hyperperfusion. Infarct volume measured 24hrs post-stroke was significantly reduced in animals that received ketamine.This study highlights the potential of gSGFETs for stroke research, as well as offering mechanistic understanding to the neuroprotective mechanisms of ketamine.

Unique ID: fens-24/ketamine-prevents-inverse-haemodynamic-5745eea3