Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage

Abstract

Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for “experimental secondary ischemia” (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies.

Hippocampal Transcriptome Changes After Subarachnoid Hemorrhage in Mice

“…We used cutoff for DEGs of 0.1, which left out a large number of genes demonstrating sizable increase in expression. Second, the only time point, 4 days, chosen because this is the point when SAH-induced delayed cerebral ischemia (DCI) starts to occur ( 23 , 24 ). These events have not been well characterized and need further investigations.…”

“…Cellular and molecular perturbations accompanying early brain injury (within 72 h post-ictus) after sub-arachnoid have been well documented in the literature and reported non-specific response to brain insult ( 21 , 22 ). However, mechanisms and respective pathways, underlying secondary brain injury, attributed to neurological and neurocognitive complications, taken place after 72 h have not been well characterized ( 23 , 24 ). In the present study, we aim to explore biological processes and secondary mechanisms at the cusp between degeneration and regeneration happening at 4 days ( 25 , 26 ) following SAH, closely mimicking delayed cerebral ischemia observed in humans ( 23 ) to explore processes at the origin of long-term consequences of SAH.…”

ASK1 inhibitor NQDI‑1 decreases oxidative stress and neuroapoptosis via the ASK1/p38 and JNK signaling pathway in early brain injury after subarachnoid hemorrhage in rats

“…After perfusion of 4°C saline from the heart to remove blood from the brain tissue, intact brain tissue was obtained. Previous studies have reported that the SAH model, induced via left-sided endovascular puncture, results in a degree of bias towards bleeding events and can be relatively severe in terms of damage to left-sided brain tissue ( 30 ). Therefore, the left-sided brain tissue was used to assess the pathological damage following SAH modeling.…”

The impairment of intramural periarterial drainage in brain after subarachnoid hemorrhage

“…After SAH, the blood cell lysates in the CSF (such as the macro-molecule methemoglobin and micro-molecule heme) flow into the ISS through PVS. These lysates trigger inflammatory reactions and apoptotic processes, resulting in neuro-vascular unit injury, such as disruption of blood brain-barrier (BBB), apoptosis of endothelial cells and neurons, brain edema and cerebral vasospasm [ 13 , 29 ].…”