Previous work in ischemic stroke has demonstrated that inherent genetic differences in mice can contribute to differences in cerebral infarction [6]. Other studies have also identified differences across mouse strains in performance during the Morris water maze [17], neurogenesis [16], and natural brain and vascular anatomy [1, 4, 7, 10, 11, 17, 20]. Here we show that genetic background in seven inbred mouse strains can contribute to variation in the severity of aVSP and neuronal injury after experimental SAH.

In the current experiments, aVSP and brain injury were assessed in C57BL/6J, BALB/c, DBA/2J, FVB/NJ, A/J, KK/HIJ, and 129S1/SvImJ mouse strains. Forty-eight hours after SAH, strains showed differences in the severity of MCA VSP. All strains differed significantly from sham controls, except DBA/2J and KK/HIJ mouse strains (Student’s t-test, P < 0.05). 129S1/SvImJ mice had the least aVSP (largest MCA radius/wall thickness ratio), whereas FVB/NJ mice had the greatest aVSP (smallest MCA radius/wall thickness ratio); however, these differences were not statistically significant (Fig. 1). Differences across strains were also observed in terms of the total number of fluoro-jade B-positive neurons. All mice differed significantly from sham controls, with KK/HIJ and C57BL/6J mice showing the most and least neuronal degeneration, respectively (ANOVA, Fisher LSD, P < 0.05; Fig. 2).

These underlying strain characteristics have important implications for the conduct of studies using mouse models. These findings suggest that because differences in VSP and brain injury have at least some genetic basis, experimental findings between different mouse strains should be compared with caution. Also, although transgenic technology is useful for the study of specific gene function, these mice are often a hybrid of multiple strains. Therefore, the amalgamation of traits may alter the reported levels of aVSP or neuronal injury, rather than what may be seen in the strain’s natural state. It is suggested that backcrossing over 12 generations can eliminate genetic heterogeneities; however, this may not be sufficient if genes responsible for stroke sensitivity are located close to the mutated genes of interest [5]. Therefore, avoiding interstrain crosses may give the truest representation of results.

Across numerous mouse studies, the C57BL/6J strain tends to be more successful at enduring injury compared with other strains [6, 8, 11, 17]. This has implications for future experimental models. The C57BL/6J strain is most common in SAH studies, so the degree of brain injury and aVSP detected may be less than if other strains were used. Identifying the most appropriate strain to model human SAH is important for translational studies. It is possible that a strain exhibiting more brain injury may be a better representation of clinical SAH because approximately 10–15 % of patients with spontaneous aneurysmal SAH die before reaching the hospital [19]. More importantly, identifying the genetic basis for the variation in aVSP and brain injury between strains may lead to insight into the pathogenesis of these complications and potentially even to treatments for SAH.