HEPARIN INHIBITS LEUKOCYTE ROLLING IN PIAL VESSELS AND ATTENUATES INFLAMMATORY CHANGES IN A RAT MODEL OF EXPERIMENTAL BACTERIAL-MENINGITIS

Heparin is a natural proteoglycan that was first described in 1916. In addition to its well characterized effect on blood coagulation, it is becoming clear that heparin also modulates lates inflammatory process es on several levels, including the interference with leukocyte-endoth elium interaction. Anecdotal observations suggest a better clinical ou tcome of heparin-treated patients with bacterial meningitis. The autho rs demonstrate that heparin, a glycosaminoglycan, inhibits significant ly in the early phase of experimental pneumococcal meningitis the incr ease of 1) regional cerebral blood flow (125 +/- 18 versus 247 +/- 42% ), 2) intracranial pressure (4.5 +/- 2.0 versus 12.1 +/- 2.2 mm Hg), 3 ) brain edema (brain water content: 78.23 +/- 0.33 versus 79.49 +/- 0. 46%), and 4) influx of leukocytes (571 +/- 397 versus 2400 +/- 875 cel ls/mu L) to the cerebrospinal fluid compared with untreated rats. To e lucidate the possible mechanism of this observation, the authors inves tigated for the first time leukocyte rolling in an inflammatory model in brain venules by confocal laser scanning microscopy in vivo. Hepari n significantly attenuates leukocyte rolling at 2, 3, and 4 hours (2.8 +/- 1.3 versus 7.9 +/- 3.2/100 mu m/min), as well as leukocyte sticki ng at 4 hours (2.1 +/- 0.4 versus 3.5 +/- 1.0/100 mu m/min) after meni ngitis induction compared with untreated animals. The authors conclude that heparin can modulate acute central nervous system inflammation a nd, in particular, leukocyte-endothelium interaction, a key process in the cascade of injury in bacterial meningitis. They propose to evalua te further the potential of heparin in central nervous system inflamma tion in basic and clinical studies.