Effects of estrogen on leukocyte adhesion after transient forebrain ischemia.
OBJECTIVE
Recent findings indicate that estrogen (ie, 17beta-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 results demonstrate that estrogen modulates leukocyte adhesion in the cerebral circulation after transient forebrain ischemia. This effect suggests that decreased leukocyte adhesion may be an important mechanism in estrogen-mediated neuroprotection.
Santizo
R A
RA
Neuroanesthesia Research Laboratory, Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60607, USA. rasp@uic.edu
Anderson
S
S
Ye
S
S
Koenig
H M
HM
Pelligrino
D A
DA
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes; D007962:Leukocytes / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010052:Ovariectomy; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D015424:Reperfusion; D012235:Rhodamines; D012884:Skin Window Technique
D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D012235:Rhodamines; C026188:rhodamine 6G; D004958:Estradiol