Table 1 Evidence of protective vascular effects of sex hormones in vitro and in adult rodent studies

Estrogen

in vitro

Human vascular BECs cultures exposed to 17β-estradiol

N/A

17β-estradiol induced biphasic effect on tight junctions and paracellular permeability

[228]

in vitro

Mouse brain microvascular endothelial cell cultures exposed to 17β-estradiol

N/A

Identification of an estrogen-responsive element at the Claudin-5 protein promoter, confirming the ability of 17β-estradiol to modulate BBB permeability

[84, 228]

in vivo

Ovariectomized (OVX) female mice treated with estradiol via subcutaneous osmotic mini-pump

ERβ knockout female mice

3-months old

Estradiol-treated ovariectomized mice had significantly increased levels of Claudin-5 protein in the brain, compared to sham-operated mice

Brain levels of Claudin-5 were significantly decreased in ERβ knockout vs. wild type animals

[228]

in vivo

Female rats after ovariectomy (OVX) + estrogen replacement

Young (4 months) vs old (9–11 months)

Estrogen replacement rescued BBB integrity in young but not old female rats

[229]

Testosterone

in vivo

Gonadectomized male mice treated with testosterone via subcutaneous implants

(5 weeks)

2-months old

Gonadectomy increased BBB permeability and altered expression of tight junction proteins in the medial preoptic area. Testosterone supplementation rescued BBB integrity

[230]

in vivo

Male Wistar rats treated with testosterone intramuscularly

6-weeks old

Testosterone supplementation compromised blood-spinal cord barrier integrity by decreasing protein expression of several tight junction proteins in the spinal cord

[230]