Wm. Clark et al., THE INFLUENCE OF ANTIADHESION THERAPIES ON LEUKOCYTE SUBSET ACCUMULATION IN CENTRAL-NERVOUS-SYSTEM ISCHEMIA IN RATS, Journal of molecular neuroscience, 6(1), 1995, pp. 43-50
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.