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 (Mφ) 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 Mφ in untreated animals that was significantly decreased with either treatment. At 4 d after ischemia no PMN were identified, with extensive Mφ 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 Mφ infiltration at 24 h. Delayed Mφ accumulation occurs despite treatment, suggesting that some of these cells represent transformed resident microglia.