Effects of Estrogen on Leukocyte Adhesion After Transient Forebrain Ischemia

Abstract

Background and Purpose-Recent findings indicate that estrogen (ie, 17␤-estradiol [E 2 ]) provides neuroprotection in models of transient global and focal ischemia. Enhanced postischemic leukocyte adhesion and infiltration have been linked to neuropathology in the brain as well as other tissues. We recently showed that estrogen reduces leukocyte adhesion in the cerebral circulation of female rats during resting conditions. Methods-We compared leukocyte adhesion in pial venules in vivo in intact, ovariectomized (OVX), and E 2 -treated OVX female rats subjected to transient forebrain ischemia (30-minute right common carotid artery occlusion and hemorrhagic hypotension) and reperfusion. Adherent rhodamine-6G-labeled leukocytes were viewed through a closed cranial window with the use of intravital microscopy. Leukocyte adhesion was measured before ischemia and at different times after reperfusion. Results-Before ischemia, leukocyte adhesion (measured as a percentage of venular area occupied by adherent leukocytes) was 2 to 3 times greater in OVX versus intact or E 2 -treated OVX rats (7.0%, 3.4%, and 2.2%, respectively). This difference disappeared at 120 minutes of reperfusion, when comparable levels of enhanced leukocyte adhesion were observed in all groups. In OVX rats, leukocyte adhesion remained elevated after 4 and 6 hours of reperfusion (11.6% and 12.9%, respectively), while the other 2 groups showed significantly lower levels (5.0% and 5.8% for intact rats and 7.0% and 7.2% for E 2 -treated OVX rats). Conclusions-Present

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

“…In hypercholesterolemic rabbits, monocyte adhesion to endothelial cells and transendothelial migration is retarded in females compared with male animals; an effect likely due to female sex hormone activity since ovariectomy enhances cell adhesion while supplementation of these animals with 17b-estradiol restores protection (Nathan et al 1999). This protective effect of sex is reproduced in other inflammatory models, again including ischemia-reperfusion injury, where, for instance, female sex hormones decrease leukocyte adhesion in response to a transient forebrain ischemic insult (Santizo et al 2000). In addition, 17b-estradiol reduces the granulocyte and monocyte/macrophage populations of injured vessels and limits leukocyte entry from adventitial/ periadventitial tissues into injured vessels, thereby reducing the neointimal response to vascular injury .…”

T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune Encephalomyelitis

“…[12][13][14] Additionally, and of relevance to central nervous system (CNS) autoimmune disease, a direct neuroprotective effect of E2 has also been demonstrated. [15][16][17] These effects of estrogen are mediated through specific receptors and depend on regulated expression and cellular distribution of these receptors. 18 We have shown recently that estrogen receptor-␣ (Esr1) is crucial for the beneficial therapeutic effect of 17␤-estradiol (E2) in murine experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.…”

Microvascular reactions of normal and osteoporotic bones in response to surgical interventions

“…In fact, there is currently no consensus on the magnitude or pathologic role of leukocyte adhesion in nonskeletal tissues after OVX. OVX has been reported to enhance PMN accumulation in the brain of resting animals (Santizo et al, 2000) but other data indicated that OVX does not influence the PMN adherence in the brain tissue after transient ischemia (Xu et al, 2004). We suggest that these differences in baseline leukocyte adhesion might be explained by the different timelines.…”

“…In our model, typical reactions after OVX, such as weight gain and osteopenia, reproducibly evolved, and the reversing efficacy of E2 therapy on osteopenia, together with the periosteal microcirculatory status of the tibia, could subsequently be evaluated in a clinically relevant, long-term period. OVX-related vascular alterations have already been demonstrated in certain organs (Santizo RA 2000;Watanabe Y 2001), but never in the periosteum. For instance, OVX has reduced the blood flow in the bone (Kapitola J 1995) and a lower total capillary density was observed in the heart (Jesmin S 2002) and brain (Jesmin S 2003), a phenomenon probably related to the well-known effect of oestrogen on angiogenesis.…”

“…With this technique, the consequences of an estrogen deficit and estrogen replacement have already been demonstrated in certain organs (Santizo et al, 2000;Watanabe et al, 2001), but never in the periosteum, though the protecting and feeding functions of the periosteum are hallmarked by the fact that restoration of periosteal microcirculation guarantees bone survival even in an environment with limited blood supply . Additionally, osteoporosis has been shown to develop on the basis of an imbalance between bone resorption and formation, the effector cells being derived from mesenchymal osteoprogenitor cells found in the periosteum and endosteum, the former displaying predominance in this respect .…”