THE INFLUENCE OF ANTIADHESION THERAPIES ON LEUKOCYTE SUBSET ACCUMULATION IN CENTRAL-NERVOUS-SYSTEM ISCHEMIA IN RATS

Although treatment with agents that block leukocyte function, includin g anti-ICAM-1 and doxycycline, reduces experimental central nervous sy stem (CNS) ischemic injury, it is not known how leukocyte subset accum ulation is affected by these agents. Using the rat two-vessel occlusio n model and immunohistochemistry, we investigated granulocyte (PMN) an d 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 wer e observed in sham animals. At 24 h postischemia, there was a moderate infiltration of PMN and M phi in untreated animals that was significa ntly decreased with either treatment. At 4 d after ischemia no PMN wer e identified, with extensive M phi accumulation occurring in untreated animals that was only partially reduced with doxycycline treatment. T hese 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 represen t transformed resident microglia.