TABLE 2.

Sex differences of NVU in ischemic stroke.

Cell	Sex Dimorphisms	Reference
Neuron	• Neuronal apoptosis in male neurons are independent of PARP-1. • Neuronal apoptosis in female neurons are associated with caspase cascades. • Estrogen suppresses neuronal autophagy in response to hypoxia or ischemia. • Loss of estrogen in aged females leads to more serious neuronal death and weakened neurogenesis	Du et al., 2004; McCullough et al., 2005; Szabo et al., 2006; Renolleau et al., 2007; Lang and McCullough, 2008; Li et al., 2017; Patrizz et al., 2021
Astrocyte	• Positive feedback production of estrogen is observed only in female astrocytes. • Female astrocytes have higher activity of P450, which catalyzes production of estrogen. • Estrogen enhances levels of GLT-1 and GLAST, who participate to clearance of glutamate. • Estrogen suppresses pro-inflammatory effects of astrocytes. • Estrogen reduces GFAP level and inhibits astrocytic activation. • Estrogen treatment to aged astrocytes exerts neurotoxicity effects because of reduced IFG-1.	Pawlak et al., 2005; Liu et al., 2007, 2008; Micevych et al., 2007; Arias et al., 2009; Lee et al., 2009; Kuo et al., 2010; Selvamani and Sohrabji, 2010; Chisholm and Sohrabji, 2016
Vessel	• Estrogen suppresses activity of NADPH-oxidase and reduces mitochondrial ROS production in endothelial cells. • Estrogen produces eNOS and PGI2 to dilate vessels, while testosterone generates TxA2 to constrict vessels. • Estrogen reduces BBB permeability. • Estrogen inhibits platelet activation and aggregation. • Estrogen replenish elevates risk of thrombosis by activating coagulating cascades in aged females.	Hayashi et al., 1995; Rubanyi et al., 2002; Gonzales et al., 2005; Liu et al., 2005; Krause et al., 2006; Miller et al., 2007; Duckles and Krause, 2011; Sohrabji et al., 2013; Roy-O’Reilly and McCullough, 2014