Meta-review on Perforation Model of Subarachnoid Hemorrhage in Mice: Filament Material as a Possible Moderator of Mortality

Abstract

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction < 24 h). Reported mean SAH grade was 10.7 [9.6, 11.7] on the scale of Sugawara (J Neurosci Methods 167:327–34, 2008). Furthermore, mean diameter of large cerebral arteries after SAH was reduced by 27.6% compared to sham-operated non-SAH mice. Uniforming standards of experimental procedures and their reporting are indispensable to increase overall comparability.

Cisterna Magna Injection Mouse Model of Subarachnoid Hemorrhage (SAH): A Systematic Literature Review of Preclinical SAH Research

“…Indeed, existing literature in this review confirmed this vasospastic effect of blood in subarachnoid space with a reduction of cerebral arteries diameter of 47 to 89% with its peak at six to twelve hours after SAH and the reaching of pre-SAH values after four to seven days. Our systematic review and meta-analysis of the filament perforation SAH mouse model showed similar values for vasospasm from 50 to 90 percent of the non-SAH arteries diameters [20]. However, SAH-grade was not mentioned for the cisterna magna blood injection model in any of the included publication.…”

“…Thereby, the mortality rate after different periods of observation after SAH ranged from 0% to 22% at 24 hours after injection procedure into the cisterna magna with autologous blood displaying the overall trend of lower mortality rates compared to the filament perforation model of SAH which is around 20 to 30% [20,30]. As the vasospasm of large cerebral arteries is triggered through blood in the subarachnoid space to prevent the extravasation of a bigger amount of blood and increased ICP, we extracted data of arteries diameters in mice with and without injected autologous blood into the cisterna magna.…”

“…To prove if this is the case and reproducibility is given, we suggest that research labs should conduct a confirmatory SAH grade evaluation study at least once for each SAH model used and present the results in published literature. For such an evaluation, we suggest using the grading system introduced by Sugawara et al [29], which is already often used in the endovascular perforation model to confirm successful introduction of SAH [20]. They divided the basal cistern into six segments and the final score was calculated by summing up the values of each segment and evaluated it according to the scale of 0-7 for mild SAH, 8-12 for moderate SAH and 13-18 to severe SAH.…”

“…The cisterna magna blood injection mouse model of SAH is considered as a replicable, low mortality model compared with the endovascular perforation mouse model [33,34]. Saito and his colleagues [35] and a previous review of our own group [20] identified that the endovascular perforation model resulted in relatively high mouse mortality rates (19-29%) while in the cisterna magna injection model mice had a mortality of mostly under 20%. Possible reasons for the slightly lower mortality in the injection model might be that the quality and quantity of injected blood can be controlled more precisely with a defined volume of blood injected into the subarachnoid space.…”

“…Among those different methods to investigate SAH, our review focusses on published literature describing experiments using the cisterna magna blood injection model. As missing standards in model characteristics and insufficient reproducibility of results have already been shown for the filament perforation SAH mouse model and for in vivo models of SAH in general [18][19][20], we analyze whether these concerns are also applicable for the cisterna magna blood injection model and discuss how researchers can face them, if applicable. Moreover, we provide an overview about animal mortality and large artery vasospasm in this model.…”