title: Heparin inhibits leukocyte rolling in pial vessels and attenuates inflammatory changes in a rat model of experimental bacterial meningitis.
abstract: 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 inflammatory processes on several levels, including the interference with leukocyte-endothelium interaction. Anecdotal observations suggest a better clinical outcome of heparin-treated patients with bacterial meningitis. The authors demonstrate that heparin, a glycosaminoglycan, inhibits significantly in the early phase of experimental pneumococcal meningitis the increase 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 cells/microL) to the cerebrospinal fluid compared with untreated rats. To elucidate the possible mechanism of this observation, the authors investigated for the first time leukocyte rolling in an inflammatory model in brain venules by confocal laser scanning microscopy in vivo. Heparin significantly attenuates leukocyte rolling at 2, 3, and 4 hours (2.8 +/- 1.3 versus 7.9 +/- 3.2/100 microm/min), as well as leukocyte sticking at 4 hours (2.1 +/- 0.4 versus 3.5 +/- 1.0/100 microm/min) after meningitis induction compared with untreated animals. The authors conclude that heparin can modulate acute central nervous system inflammation and, in particular, leukocyte-endothelium interaction, a key process in the cascade of injury in bacterial meningitis. They propose to evaluate further the potential of heparin in central nervous system inflammation in basic and clinical studies.
authors.affiliation: Department of Neurology, Universitätsklinikum Charité, Humboldt University, Berlin, Germany.
authors.forename: J R
authors.initials: JR
authors.lastname: Weber
authors.forename: K
authors.initials: K
authors.lastname: Angstwurm
authors.forename: T
authors.initials: T
authors.lastname: Rosenkranz
authors.forename: U
authors.initials: U
authors.lastname: Lindauer
authors.forename: D
authors.initials: D
authors.lastname: Freyer
authors.forename: W
authors.initials: W
authors.lastname: Bürger
authors.forename: C
authors.initials: C
authors.lastname: Busch
authors.forename: K M
authors.initials: KM
authors.lastname: Einhäupl
authors.forename: U
authors.initials: U
authors.lastname: Dirnagl
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001929:Brain Edema / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D007427:Intracranial Pressure / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016920:Meningitis, Bacterial / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D006493:Heparin; D006497:Heparan Sulfate