Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1999 Aug;67(2):185–188. doi: 10.1136/jnnp.67.2.185

Detection of meningeal fibrosis after subarachnoid haemorrhage by assaying procollagen propeptides in cerebrospinal fluid

J Sajanti 1, K Majamaa 1
PMCID: PMC1736496  PMID: 10406986

Abstract

OBJECTIVE—To study whether meningeal collagen synthesis under normal conditions is reflected in the CSF and whether a meningeal fibroproliferative reaction or fibrosis after subarachnoid haemorrhage can be detected by measuring markers of collagen synthesis in the CSF.
METHODS—Serum samples and CSF were collected from 56 patients with various neurological symptoms and from nine patients with a recent subarachnoid haemorrhage. The concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured using radioimmunoassays.
RESULTS—The mean(SD) concentration of PICP was 75.2 (SD 13.6) µg/l and that of PIIINP 3.56 (SD 0.91) µg/l in the CSF of the controls, and the CSF/serum ratios were 0.74 (SD 0.24) for PICP and 1.34(SD 0.48) for PIIINP. A 1.4-fold increase in both the PICP (p=0.001) and the PIIINP (p=0.001) concentration was found in patients with a neurological disease and with an abnormal CSF leucocyte count or protein concentration. In eight patients with a recent subarachnoid haemorrhage the PICP was 5.9-fold higher (p<0.001) and the PIIINP concentration 7.7-fold higher (p<0.001) than that in the controls, whereas no difference was found in the serum values. Similar high concentrations were also found in a patient from whom the CSF sample was obtained before operation for aneurysm.
CONCLUSIONS—The intrathecal compartment is a site for active collagen synthesis under normal conditions. The synthesis rate is markedly increased in patients with a recent subarachnoid haemorrhage, suggesting a fibroproliferative reaction or fibrosis. Assays of procollagen propeptides may be useful in the clinical diagnosis of meningeal fibrosis and their use may enable the identification of diseases and symptoms aetiologically related to meningeal fibrosis.



Full Text

The Full Text of this article is available as a PDF (71.4 KB).

Selected References

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

  1. Ala-Kokko L., Pihlajaniemi T., Myers J. C., Kivirikko K. I., Savolainen E. R. Gene expression of type I, III and IV collagens in hepatic fibrosis induced by dimethylnitrosamine in the rat. Biochem J. 1987 May 15;244(1):75–79. doi: 10.1042/bj2440075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blödorn B., Mäder M., Urade Y., Hayaishi O., Felgenhauer K., Brück W. Choroid plexus: the major site of mRNA expression for the beta-trace protein (prostaglandin D synthase) in human brain. Neurosci Lett. 1996 May 10;209(2):117–120. doi: 10.1016/0304-3940(96)12614-8. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Clark J. G., Overton J. E., Marino B. A., Uitto J., Starcher B. C. Collagen biosynthesis in bleomycin-induced pulmonary fibrosis in hamsters. J Lab Clin Med. 1980 Dec;96(6):943–953. [PubMed] [Google Scholar]
  5. Haines D. E. On the question of a subdural space. Anat Rec. 1991 May;230(1):3–21. doi: 10.1002/ar.1092300103. [DOI] [PubMed] [Google Scholar]
  6. Herbert J., Wilcox J. N., Pham K. T., Fremeau R. T., Jr, Zeviani M., Dwork A., Soprano D. R., Makover A., Goodman D. S., Zimmerman E. A. Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award. Neurology. 1986 Jul;36(7):900–911. doi: 10.1212/wnl.36.7.900. [DOI] [PubMed] [Google Scholar]
  7. Hijdra A., Brouwers P. J., Vermeulen M., van Gijn J. Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke. 1990 Aug;21(8):1156–1161. doi: 10.1161/01.str.21.8.1156. [DOI] [PubMed] [Google Scholar]
  8. Hunt W. E., Hess R. M. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968 Jan;28(1):14–20. doi: 10.3171/jns.1968.28.1.0014. [DOI] [PubMed] [Google Scholar]
  9. Lignelid H., Collins V. P., Jacobsson B. Cystatin C and transthyretin expression in normal and neoplastic tissues of the human brain and pituitary. Acta Neuropathol. 1997 May;93(5):494–500. doi: 10.1007/s004010050644. [DOI] [PubMed] [Google Scholar]
  10. Meltzer C. C., Fukui M. B., Kanal E., Smirniotopoulos J. G. MR imaging of the meninges. Part I. Normal anatomic features and nonneoplastic disease. Radiology. 1996 Nov;201(2):297–308. doi: 10.1148/radiology.201.2.8888215. [DOI] [PubMed] [Google Scholar]
  11. Motohashi O., Suzuki M., Shida N., Umezawa K., Ohtoh T., Sakurai Y., Yoshimoto T. Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space. Immunhistochemical study. Acta Neurochir (Wien) 1995;136(1-2):88–91. doi: 10.1007/BF01411441. [DOI] [PubMed] [Google Scholar]
  12. Prockop D. J., Kivirikko K. I. Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem. 1995;64:403–434. doi: 10.1146/annurev.bi.64.070195.002155. [DOI] [PubMed] [Google Scholar]
  13. Raghow R., Lurie S., Seyer J. M., Kang A. H. Profiles of steady state levels of messenger RNAs coding for type I procollagen, elastin, and fibronectin in hamster lungs undergoing bleomycin-induced interstitial pulmonary fibrosis. J Clin Invest. 1985 Nov;76(5):1733–1739. doi: 10.1172/JCI112163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Risteli J., Kivirikko K. I. Intracellular enzymes of collagen biosynthesis in rat liver as a function of age and in hepatic injury induced by dimethylnitrosamine. Changes in prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase activities. Biochem J. 1976 Aug 15;158(2):361–367. doi: 10.1042/bj1580361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Risteli J., Risteli L. Analysing connective tissue metabolites in human serum. Biochemical, physiological and methodological aspects. J Hepatol. 1995;22(2 Suppl):77–81. [PubMed] [Google Scholar]
  16. Rutka J. T., Giblin J., Dougherty D. V., McCulloch J. R., DeArmond S. J., Rosenblum M. L. An ultrastructural and immunocytochemical analysis of leptomeningeal and meningioma cultures. J Neuropathol Exp Neurol. 1986 May;45(3):285–303. doi: 10.1097/00005072-198605000-00012. [DOI] [PubMed] [Google Scholar]
  17. Scharffetter K., Kulozik M., Stolz W., Lankat-Buttgereit B., Hatamochi A., Söhnchen R., Krieg T. Localization of collagen alpha 1(I) gene expression during wound healing by in situ hybridization. J Invest Dermatol. 1989 Sep;93(3):405–412. [PubMed] [Google Scholar]
  18. Suzuki S., Ishii M., Iwabuchi T. Post-haemorrhagic subarachnoid fibrosis in dogs. Scanning electron microscopic observation and dye perfusion study. Acta Neurochir (Wien) 1979;46(1-2):105–117. doi: 10.1007/BF01407685. [DOI] [PubMed] [Google Scholar]
  19. Suzuki S., Ishii M., Ottomo M., Iwabuchi T. Changes in the subarachnoid space after experimental subarachnoid haemorrhage in the dog: scanning electron microscopic observation. Acta Neurochir (Wien) 1977;39(1-2):1–14. doi: 10.1007/BF01405236. [DOI] [PubMed] [Google Scholar]
  20. Thompson E. J., Keir G. Laboratory investigation of cerebrospinal fluid proteins. Ann Clin Biochem. 1990 Sep;27(Pt 5):425–435. doi: 10.1177/000456329002700503. [DOI] [PubMed] [Google Scholar]
  21. Tu G. F., Achen M. G., Aldred A. R., Southwell B. R., Schreiber G. The distribution of cerebral expression of the transferrin gene is species specific. J Biol Chem. 1991 Apr 5;266(10):6201–6208. [PubMed] [Google Scholar]
  22. Vainionpä L., Risteli L., Lanning M., Risteli J. Carboxyterminal propeptide of type I procollagen in cerebrospinal fluid in childhood and in children with leukemia undergoing intrathecal treatment. Clin Chem. 1991 Aug;37(8):1365–1369. [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES