Table 4.

Preclinical studies examining sex-specific differences in neutrophil and lymphocyte responses in ischemic stroke

Study	Species and strain	Age	Key findings
Xiong et al. [131]	BALB/cJ and IL-4 KO (BALB/c-IL-4tm2Nnt/J) mice	10–12 weeks	During estrous, WT female mice have significantly lower T cells, but this difference was lost with deletion of IL4
Banerjee et al. [76]	C57BL/6 J mice	Not reported	Post-stroke, spleens of male mice become severely atrophic. Male spleens had higher CD8+CD122+ T-suppressor cells, whereas female spleens had higher IL-10 secreting CD8+CD122+ T-suppressor cells. There was a higher percentage of VLA-4 expression on male mice lymphocytes
Manwani et al. [193]	C57BL/6 mice	5–6 months, 14–15 months, and 20–22 months	Stroke leads to splenic contraction in male mice of all ages and aged female mice. Similarly, male mice with stroke had higher levels of T cells when compared with female mice, except in elderly mice, where the difference disappeared
Dotson et al. [74]	C57BL/6 J mice	-	Prior to splenectomy, male mice had larger stroke volumes than female mice. After splenectomy, male mice had reduced stroke volume, and there was no longer a difference in male and female mice stroke volume. Spleen intact females have lower CD4 + T cells and lower number of “activated” T cells than males, a difference lost with splenectomy
Brait et al. [184]	C57BL/6 J mice	6–8 weeks	Male mice have a higher CD3+ T cell response with increased Nox2 expression resulting in larger infarcts than those in female mice
Seifert et al. [75]	C57BL/6 J mice	8–10 weeks	Post-MCAO, female mice had smaller infarct volumes. This was likely due to higher frequency of B10, CD19+CD5+CD1dhi cells. Female mice also have decreased Breg cells and increased Treg in their spleen after MCAO
Ahnstedt et al. [80]	C57BL/6 N mice	20–22 months	Increased CD8+ T cells and Tregs in infarcts of aged males. No sex difference in CD4+ T cells
Jackson et al. [196]	Wistar rats	12–15 weeks	After stroke, the blood of male mice had a higher percentage of circulating γδTCR and TH1 cells, but lower Treg when compared to females In the brain, males had a higher percentage of TH1 cells. Diabetes also had a sexually dimorphic effect on regulation of various T cell subtypes

IL interleukin, VLA very late antigen, MCAO middle cerebral artery occlusion