Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke

Abstract

The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies).The tMCAO monitoring data (bilateral cerebral blood flow - CBF, heart rate - HR, mean arterial pressure - MAP) of 16 animals with an “ideal” outcome (MCA-ischemia) and 48 animals with additional or other pathologies (subdural hematoma or subarachnoid hemorrhage) were checked for their prognostic performance (receiver operating characteristic curve and area under the curve - AUC).Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP in addition to baseline HR (AUC 0.83, 95% CI 0.68 to 0.97) increased prognostic relevance (AUC 0.89, 95% CI 0.79 to 0.98). Prediction performance improved when two additional predictors referring differences in left and right CBF were considered (AUC 1.00, 95% CI 1.0 to 1.0).Our data underline the importance of periinterventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.

Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO)

“…In humans, it has also been stated that the cognitive impairment rate in stroke survivors was strongly associated with age 48 . Taken together, considering the potential possibility of spontaneous recovery after stroke in different functional outcomes, a battery of neurological and behavioral assessments would be beneficial to draw a panorama of the functional protective effect of potential treatments 47,51 . Related to the present study, more behavioral measures with respect to different aspects of sensorimotor function, such as Rotarod, Cylinder test, Catwalk test and Forelimb placing, are needed in future 46,47 .…”

“…The design of a 3 h-delayed argon administration after stroke onset is more relevant to clinical practice 3 and would provide valuable data to guide the development of new therapeutic strategies for patients. In addition, continuous perioperative monitoring, especially the bilateral rCBF assessment, assured experimental quality and eliminate falsification of the experimental results by including undesired pathologies 51 . For the first time, to the best of our knowledge, the long-term effects of argon after ischemic stroke were explored.…”

“…Meanwhile, the functional tests being used should be chosen carefully and a battery of neurological and behavioral assessments would be beneficial to reveal the potential protective property of the therapeutic regimen. Computer-assisted and automated systems may offer an additional objective evaluation 51,52 .…”