The influence of antiadhesion therapies on leukocyte subset accumulation in central nervous system ischemia in rats.
Although treatment with agents that block leukocyte function, including anti-ICAM-1 and doxycycline, reduces experimental central nervous system (CNS) ischemic injury, it is not known how leukocyte subset accumulation is affected by these agents. Using the rat two-vessel occlusion model and immunohistochemistry, we investigated granulocyte (PMN) and monocyte/macrophage (M phi) accumulation at 1 and 4 d postischemia. A total of 24 animals were randomized to sham surgery, or to ischemia with saline, anti-ICAM-1, or doxycycline treatments. No leukocytes were observed in sham animals. At 24 h postischemia, there was a moderate infiltration of PMN and M phi in untreated animals that was significantly decreased with either treatment. At 4 d after ischemia no PMN were identified, with extensive M phi accumulation occurring in untreated animals that was only partially reduced with doxycycline treatment. These results confirm that both anti-ICAM-1 and doxycycline treatments reduce PMN and M phi infiltration at 24 h. Delayed M phi accumulation occurs despite treatment, suggesting that some of these cells represent transformed resident microglia.
Clark
W M
WM
Oregon Stroke Center, Department of Neurology, Oregon Health Sciences University, Portland, USA.
Lauten
J D
JD
Lessov
N
N
Woodward
W
W
Coull
B M
BM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000276:immunology; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D004318:Doxycycline / Q000494:pharmacology; D007150:Immunohistochemistry; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018696:Neuroprotective Agents; D004318:Doxycycline