Inflammatory and hemodynamic changes in the cerebral microcirculation of aged rats after global cerebral ischemia and reperfusion.
Effects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19-22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia-reperfusion (I-R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/-fMLP). In I-R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood-shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I-R in the aged brain.
Ritter
Leslie
L
College of Nursing, The University of Arizona, Tucson, Arizona 85721, USA. lritter@nursing.arizona.edu
Funk
Janet
J
Schenkel
Lori
L
Tipton
Alicia
A
Downey
Kate
K
Wilson
Jonathan
J
Coull
Bruce
B
McDonagh
Paul
P
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000378:metabolism* / Q000473:pathology; D006439:Hemodynamics; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D039481:CD11b Antigen