Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jul;82(1):102–109. doi: 10.1172/JCI113556

Role of cerebrospinal fluid pleocytosis and Haemophilus influenzae type b capsule on blood brain barrier permeability during experimental meningitis in the rat.

A J Lesse 1, E R Moxon 1, A Zwahlen 1, W M Scheld 1
PMCID: PMC303482  PMID: 3260602

Abstract

The influence of leukocytes and Haemophilus influenzae type b (Hib) capsule on blood brain barrier permeability (BBBP) to circulating 125I-albumin in normal and leukopenic rats was assessed after intracisternal inoculation of encapsulated (Rd-/b+/02) or unencapsulated (Rd-/b-/02) isogenic strains of Hib. Both normal and leukopenic animals had increased BBBP 18 h after inoculation, with normal rats demonstrating significantly increased BBBP after challenge with the encapsulated strain. Despite cerebrospinal fluid (CSF) pleocytosis in normal rats, CSF bacterial concentrations were not lower. Normal rats cleared unencapsulated Rd-/b-/02 more effectively than leukopenic rats, with BBBP correlating with CSF bacterial density and not leukocyte concentrations. Challenge with heat-killed Rd-/b+/02 resulted in increased BBBP in both normal and leukopenic rats, with greater BBBP at higher bacterial concentrations. The data suggest: (a) significant increases in BBBP occur in the near absence of CSF leukocytes; (b) CSF leukocytes can augment changes in BBBP; (c) type b capsule inhibits host clearance mechanisms within the CSF; and (d) BBBP appears to correlate with bacterial concentrations within the CSF.

Full text

PDF
102

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brightman M. W., Reese T. S. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol. 1969 Mar;40(3):648–677. doi: 10.1083/jcb.40.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chow H. S., Sarpel S. C., Epstein R. B. Pathophysiology of Candida albicans meningitis in normal, neutropenic, and granulocyte transfused dogs. Blood. 1980 Apr;55(4):546–551. [PubMed] [Google Scholar]
  3. Ernst J. D., Decazes J. M., Sande M. A. Experimental pneumococcal meningitis: role of leukocytes in pathogenesis. Infect Immun. 1983 Jul;41(1):275–279. doi: 10.1128/iai.41.1.275-279.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Faustmann P. M., Dermietzel R. Extravasation of polymorphonuclear leukocytes from the cerebral microvasculature. Inflammatory response induced by alpha-bungarotoxin. Cell Tissue Res. 1985;242(2):399–407. doi: 10.1007/BF00214554. [DOI] [PubMed] [Google Scholar]
  5. Feldman W. E., Ginsburg C. M., McCracken G. H., Jr, Allen D., Ahmann P., Graham J., Graham L. Relation of concentrations of Haemophilus influenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis. J Pediatr. 1982 Feb;100(2):209–212. doi: 10.1016/s0022-3476(82)80636-7. [DOI] [PubMed] [Google Scholar]
  6. Feldman W. E. Relation of concentrations of bacteria and bacterial antigen in cerebrospinal fluid to prognosis in patients with bacterial meningitis. N Engl J Med. 1977 Feb 24;296(8):433–435. doi: 10.1056/NEJM197702242960806. [DOI] [PubMed] [Google Scholar]
  7. Giampaolo C., Scheld M., Boyd J., Savory J., Sande M., Wills M. Leukocyte and bacterial interrelationships in experimental meningitis. Ann Neurol. 1981 Apr;9(4):328–333. doi: 10.1002/ana.410090403. [DOI] [PubMed] [Google Scholar]
  8. HARTER D. H., PETERSDORF R. G. A consideration of the pathogenesis of bacterial meningitis: review of experimental and clinical studies. Yale J Biol Med. 1960 Feb;32:280–309. [PMC free article] [PubMed] [Google Scholar]
  9. Hoiseth S. K., Connelly C. J., Moxon E. R. Genetics of spontaneous, high-frequency loss of b capsule expression in Haemophilus influenzae. Infect Immun. 1985 Aug;49(2):389–395. doi: 10.1128/iai.49.2.389-395.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kimura A., Hansen E. J. Antigenic and phenotypic variations of Haemophilus influenzae type b lipopolysaccharide and their relationship to virulence. Infect Immun. 1986 Jan;51(1):69–79. doi: 10.1128/iai.51.1.69-79.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimura A., Patrick C. C., Miller E. E., Cope L. D., McCracken G. H., Jr, Hansen E. J. Haemophilus influenzae type b lipooligosaccharide: stability of expression and association with virulence. Infect Immun. 1987 Sep;55(9):1979–1986. doi: 10.1128/iai.55.9.1979-1986.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kitchens C. S., Weiss L. Ultrastructural changes of endothelium associated with thrombocytopenia. Blood. 1975 Oct;46(4):567–578. [PubMed] [Google Scholar]
  13. Lukes S. A., Posner J. B., Nielsen S., Armstrong D. Bacterial infections of the CNS in neutropenic patients. Neurology. 1984 Mar;34(3):269–275. doi: 10.1212/wnl.34.3.269. [DOI] [PubMed] [Google Scholar]
  14. McAllister C. K., O'Donoghue J. M., Beaty H. N. Experimental pneumococcal meningitis. II. Characterization and quantitation of the inflammatory process. J Infect Dis. 1975 Oct;132(4):355–360. doi: 10.1093/infdis/132.4.355. [DOI] [PubMed] [Google Scholar]
  15. Nolan C. M., McAllister C. K., Walters E., Beaty H. N. Experimental pneumococcal meningitis. IV. The effect of methyl prednisolone on meningeal inflammation. J Lab Clin Med. 1978 Jun;91(6):979–988. [PubMed] [Google Scholar]
  16. PETERSDORF R. G., LUTTRELL C. N. Studies on the pathogenesis of meningitis. I. Intrathecal infection. J Clin Invest. 1962 Feb;41:311–319. doi: 10.1172/JCI104484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pepple J., Moxon E. R., Yolken R. H. Indirect enzyme-linked immunosorbent assay for the quantitation of the type-specific antigen of Haemophilus influenzae b: a preliminary report. J Pediatr. 1980 Aug;97(2):233–237. doi: 10.1016/s0022-3476(80)80480-x. [DOI] [PubMed] [Google Scholar]
  18. Quagliarello V. J., Long W. J., Scheld W. M. Morphologic alterations of the blood-brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation. J Clin Invest. 1986 Apr;77(4):1084–1095. doi: 10.1172/JCI112407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reese T. S., Karnovsky M. J. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967 Jul;34(1):207–217. doi: 10.1083/jcb.34.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rubin L. G., Zwahlen A., Moxon E. R. Role of intravascular replication in the pathogenesis of experimental bacteremia due to Haemophilus influenzae type b. J Infect Dis. 1985 Aug;152(2):307–314. doi: 10.1093/infdis/152.2.307. [DOI] [PubMed] [Google Scholar]
  21. SWARTZ M. N., DODGE P. R. BACTERIAL MENINGITIS--A REVIEW OF SELECTED ASPECTS. 1. GENERAL CLINICAL FEATURES, SPECIAL PROBLEMS AND UNUSUAL MENINGEAL REACTIONS MIMICKING BACTERIAL MENINGITIS. N Engl J Med. 1965 Apr 8;272:725–CONTD. doi: 10.1056/NEJM196504082721406. [DOI] [PubMed] [Google Scholar]
  22. Scheld W. M., Dacey R. G., Winn H. R., Welsh J. E., Jane J. A., Sande M. A. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone. J Clin Invest. 1980 Aug;66(2):243–253. doi: 10.1172/JCI109850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schlech W. F., 3rd, Ward J. I., Band J. D., Hightower A., Fraser D. W., Broome C. V. Bacterial meningitis in the United States, 1978 through 1981. The National Bacterial Meningitis Surveillance Study. JAMA. 1985 Mar 22;253(12):1749–1754. [PubMed] [Google Scholar]
  24. Sears M. R., O'Donoghue J. M., Fisher H. K., Beaty H. N. Effect of experimental pneumococcal meningitis on respiration and circulation in the rabbit. J Clin Invest. 1974 Jul;54(1):18–23. doi: 10.1172/JCI107740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Simberkoff M. S., Moldover N. H., Rahal J., Jr Absence of detectable bactericidal and opsonic activities in normal and infected human cerebrospinal fluids. A regional host defense deficiency. J Lab Clin Med. 1980 Mar;95(3):362–372. [PubMed] [Google Scholar]
  26. Tuomanen E., Liu H., Hengstler B., Zak O., Tomasz A. The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis. 1985 May;151(5):859–868. doi: 10.1093/infdis/151.5.859. [DOI] [PubMed] [Google Scholar]
  27. Täuber M. G., Khayam-Bashi H., Sande M. A. Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis. J Infect Dis. 1985 Mar;151(3):528–534. doi: 10.1093/infdis/151.3.528. [DOI] [PubMed] [Google Scholar]
  28. Zwahlen A., Nydegger U. E., Vaudaux P., Lambert P. H., Waldvogel F. A. Complement-mediated opsonic activity in normal and infected human cerebrospinal fluid: early response during bacterial meningitis. J Infect Dis. 1982 May;145(5):635–646. doi: 10.1093/infdis/145.2.635. [DOI] [PubMed] [Google Scholar]
  29. Zwahlen A., Rubin L. G., Moxon E. R. Contribution of lipopolysaccharide to pathogenicity of Haemophilus influenzae: comparative virulence of genetically-related strains in rats. Microb Pathog. 1986 Oct;1(5):465–473. doi: 10.1016/0882-4010(86)90008-2. [DOI] [PubMed] [Google Scholar]
  30. Zwahlen A., Winkelstein J. A., Moxon E. R. Surface determinants of Haemophilus influenzae pathogenicity: comparative virulence of capsular transformants in normal and complement-depleted rats. J Infect Dis. 1983 Sep;148(3):385–394. doi: 10.1093/infdis/148.3.385. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES