Abstract
ABSTRACTProper occlusion of the medial cerebral artery, as determined by laser Doppler monitoring, during cerebral ischaemia in rat models is an important inclusion criterion in experimental studies. However, successful occlusion of the artery does not always guarantee a reproducible infarct volume, which is crucial for validating the efficacy of new protective drugs. In a rat intraluminal ischaemic model, laser Doppler monitoring alone was compared with laser Doppler monitoring in combination with magnetic resonance angiography (MRA) and diffusion-weighted imaging (DWI). Twenty-eight animals showed successful occlusion and reperfusion determined with Doppler monitoring, with an infarct size at 24 h of 16.7±11.5% (determined as ischaemic damage with respect to the ipsilateral hemisphere volume). However, when arterial occlusion and infarct damage were analysed in these animals using MRA and DWI, respectively, 15 animals were excluded and only 13 animals were included, with an infarct size at 24 h of 21.6±6.1%, showing a variability in the infarct size significantly lower (P<0.05, F-test) than that obtained with Doppler monitoring alone. We also observed that blocking of the pterygopalatine artery (a maxillary artery that is usually occluded in the intraluminal ischaemic model) was not relevant for this model, at least in terms of infarct variability. These results show that laser Doppler monitoring is a necessary procedure, but not sufficient to guarantee a reproducible infarct volume, in a rat ischaemic model. Therefore, laser Doppler monitoring in combination with DWI and MRA represents a reliable inclusion protocol during ischaemic surgery for the analysis of new protective drugs.
Highlights
The Stroke Therapy Academic Industry Roundtable (STAIR) criteria have been updated periodically since their creation, with the purpose of improving the quality of preclinical studies on acute stroke therapies (Saver et al, 2013; Stroke Therapy Academic Industry Roundtable, 1991)
In this study, two different experimental inclusion protocols were compared: (1) inclusion of animals based on laser Doppler monitoring: animals with cerebral blood flow (CBF) reduction >70% and complete reperfusion (>60%) after MCAo determined only with laser Doppler monitoring; (2) inclusion of animals based on laser Doppler and MRI (DWI and magnetic resonance angiography (MRA)) monitoring during MCAo: animals with CBF reduction >70% determined with laser Doppler monitoring, diffusion-weighted imaging (DWI) hemispheric infarct volume between 25% and 45%, MRA of the MCAo, and complete reperfusion after MCAo
Analysis of the ischaemic damage determined at 24 h showed that the infarct size in those animals included following the criterion of laser Doppler alone was 16.7± 11.5%, whereas in those animals included based
Summary
The Stroke Therapy Academic Industry Roundtable (STAIR) criteria have been updated periodically since their creation, with the purpose of improving the quality of preclinical studies on acute stroke therapies (Saver et al, 2013; Stroke Therapy Academic Industry Roundtable, 1991). One of the most crucial STAIR recommendations is the monitoring of cerebral blood flow (CBF) using laser Doppler during surgery to guarantee proper medial. In preclinical studies focusing on protective strategies for the acute phase of stroke (70% or 80% from the basal levels. It is well known that the cerebral collateral circulation can supply blood to the ischaemic region that is difficult to register with the Doppler probe, and increases the internal variability of the experimental groups (Cuccione et al, 2016)
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