Procollagen Type I C-terminal propeptide, procollagen Type III N-terminal propeptide, hyaluronic acid, and laminin in the cerebrospinal fluid of rats with communicating hydrocephalus.

OBJECT: Fibrosis along the route of CSF flow is indicated by the development of hydrocephalus. The changes of fibrosis index might reflect the level of hydrocephalus and even become a diagnostic index of hydrocephalus. The object of this study was to analyze the levels of procollagen Type I C-terminal propeptide (PICP), procollagen Type III N-terminal propeptide (PIIINP), hyaluronic acid (HA), and laminin (LN) and their significance in the CSF of communicating hydrocephalus rat models. METHODS: Thirty adult Sprague-Dawley rats were randomly divided into 3 groups: hydrocephalus group (20 rats) with intraventricular kaolin injections, sham control group (5 rats) with saline injections, and normal group (5 rats) without any processing. The levels of PICP, PIIINP, HA, and LN in the CSF were detected using ELISA. RESULTS: Levels of PICP, PIIINP, HA, and LN in the hydrocephalus group were significantly higher than those in the saline control group (p < 0.05). It was revealed by correlation analysis that the increase was positively correlated with the severity of ventricular dilation. CONCLUSIONS: Results indicated that PICP, PIIINP, HA, and LN continue to rise dramatically in experimental hydrocephalus and may serve as the diagnostic index of hydrocephalus.

Procollagen I C-propeptide in the cerebrospinal fluid of neonates with posthaemorrhagic hydrocephalus.

BACKGROUND: The pathogenesis of posthaemorrhagic hydrocephalus (PHHC) following intraventricular haemorrhage (IVH) in premature infants includes a fibroproliferative reaction leading to arachnoidal fibrosis, ultimately causing malresorption of cerebrospinal fluid (CSF) at the arachnoid villi. AIMS: To determine whether an increased concentration of the carboxyterminal propeptide of type I procollagen (PICP) in the CSF of neonates after IVH reflects the activation of collagen synthesis preceding the manifestation of PHHC. METHODS: From 20 neonates with PHHC (median birth weight 740 g, median gestational age 25+1 weeks), 52 CSF samples were collected. CSF samples of four neonates (median birth weight 2170 g, median gestational age 32+4 weeks) with congenital non-haemorrhagic hydrocephalus served as controls. PICP was measured by radioimmunoassay. RESULTS: PICP in CSF taken at the start of external CSF drainage (median day 21, range 17-25 days postnatal age) was significantly increased (median 851.5, range 153.5-1944 microg/l) compared with controls (median 136.1, range 33.8-169.5 microg/l). CSF concentrations of PICP declined until permanent shunt placement (median day 70, range days 41-113). CONCLUSION: In neonates who develop PHHC, significant elevation of PICP concentration in the CSF is present 3-4 weeks after IVH. It reflects the increase of local type I collagen turnover, thereby correlating with manifestation of PHHC.

Rapid induction of meningeal collagen synthesis in the cerebral cisternal and ventricular compartments after subarachnoid hemorrhage.

Procollagen propeptides in the lumbar CSF increase after subarachnoid hemorrhage (SAH), and elevated concentrations have been detected as early as on day 8. We studied here the timing and localization of the induction of meningeal collagen synthesis during the first week after SAH by analysing cisternal and ventricular CSF samples. We obtained 29 cisternal and 10 ventricular CSF samples at operation from patients with SAH between days 1 and 9 after onset. The carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured using radio-immunoassays. The concentrations of PICP and PIIINP in the cisternal CSF were elevated as early as on day 2 after SAH. PICP increased in a sigmoidal fashion (R2 = 0.39, p < 0.001), while PIIINP increased linearly (R2 = 0.28, p = 0.003) and was approximately 3-fold higher on day 9 than initially. PICP was twice as high (p = 0.02) in the cisternal than in the ventricular CSF after SAH and PIIINP was 4-times higher (p = 0.007). Interestingly, the concentrations were similar in a patient with intraventricular bleeding. The cisternal compartment contributed to the propeptides in the CSF more than did the ventricular compartment, but the latter also appeared to have a definite potential for fibroproliferative reaction. Meningeal collagen synthesis was induced rapidly within the first few days after SAH suggesting that therapeutic attempts to inhibit the fibroproliferative reaction should be started as early as possible.

Transient increase in procollagen propeptides in the CSF after subarachnoid hemorrhage.

BACKGROUND: Meningeal fibrosis following subarachnoid hemorrhage (SAH) has been verified histologically in experimental animals and in human autopsy samples, but the clinical course of the intrathecal fibroproliferative reaction is unknown. The authors therefore studied time-related changes in the CSF concentrations of type I (PICP) and type III (PIIINP) procollagen propeptides in patients with recent SAH. METHOD: Fifty-two CSF samples were obtained from 39 patients with SAH treated surgically and eight samples from eight patients with SAH who were not surgically treated. The samples were analyzed for PICP and PIIINP by using radioimmunoassays. RESULTS: The authors found a time-dependent increase in PICP and PIIINP in the CSF of the patients with SAH. Two weeks after the hemorrhage, concentrations were four times higher in patients with SAH than the concentrations in the control subjects. Concentrations in patients with SAH then declined steadily, but remained slightly but significantly elevated even at 10 weeks. PICP and PIIINP did not correlate with the age or sex of the patient or the amount of blood in the initial CT scan. Four patients developed late posthemorrhagic hydrocephalus; their PICP and PIIINP levels were higher than in matched patients with SAH without hydrocephalus. CONCLUSIONS: Time-dependent changes in CSF concentrations of PICP and PIIINP suggest a transient fibroproliferative reaction in the meninges after SAH. The considerable magnitude and extended time course of the changes make the measurement of PICP and PIIINP practicable for the diagnosis of a fibroproliferative state in patients with recent meningeal disease. Furthermore, the results suggest a role for meningeal fibrosis in the development of late posthemorrhagic hydrocephalus.

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

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) microgram/l and that of PIIINP 3.56 (SD 0.91) microgram/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.

Aminoterminal propeptide of type III procollagen in cerebrospinal fluid. Variation with age and in childhood leukemia.

Analyses of the aminoterminal propeptide of type III procollagen (PIIINP) in the cerebrospinal fluid (CSF) of 55 children and five young adults without any structural central nervous system (CNS) lesion are reported. The concentration was age-dependent, in that infants and small children had quite high values, whereas the concentration remained relatively constant after the age of 1.5 years. The concentrations of PIIINP in the CSF of 44 children with acute lymphoblastic leukemia (ALL) were prospectively determined at the time of diagnosis and during treatment, since deposition of type III collagen is known to occur during fibroproliferative responses triggered by inflammation. Chemical arachnoiditis is known to be associated with intrathecal methotrexate therapy in children with leukemia. The mean concentration in these children at diagnosis (5.8 micrograms/l +/- SD 2.8 micrograms/l) did not differ from that in age-matched controls (6.7 micrograms/l +/- SD 3.2 micrograms/l). Depending on type of the disease, the children were treated according to two different protocols. PIIINP concentrations were significantly higher during the therapy phases which included intrathecally administered methotrexate (P less than 0.001) than at diagnosis of the disease. Corticosteroid treatments were always associated with a significant decrease in PIIINP concentrations (P less than 0.01 and P less than 0.001 in the two groups, respectively), irrespective of the therapy phase. The results suggest that an increase in PIIINP concentration in the CSF of children with ALL is an indicator of a fibroproliferative response in the arachnoid. Corticosteroids may repress this response and possibly also prevent the development of adhesions in the arachnoid.

Carboxyterminal propeptide of type I procollagen in cerebrospinal fluid in childhood and in children with leukemia undergoing intrathecal treatment.

We determined the reference interval for the carboxyterminal propeptide of type I procollagen (PICP), an indicator of the synthesis of type I collagen, in cerebrospinal fluid (CSF) by studying 32 infants and children, ages less than or equal to 15 years. The concentration of PICP is age dependent, with particularly high concentrations occurring in children younger than 1.5 years. In older children the concentration is stable (reference interval 20-92 micrograms/L). We also investigated the possibility that PICP in CSF could reflect local fibroproliferative changes in the arachnoid in a cohort of 42 children with acute lymphoblastic leukemia who were monitored by repeated sampling in connection with intrathecal therapy. Initially, there was no difference in PICP between the children with newly diagnosed leukemia and the controls. PICP concentrations were significantly higher (P less than 0.01) during intrathecal methotrexate therapy, with median values above the reference interval. Continuous corticosteroid treatment was associated with a significant decrease in PICP (P less than 0.02 and P less than 0.01, respectively, in two groups treated according to different protocols), close to the lower limit of the reference interval. Intrathecally administered methotrexate and systemic corticosteroid treatment are known to be associated with the development of arachnoiditis and with general repression of collagen synthesis, respectively. We conclude that PICP in CSF is a sensitive indicator of local fibroproliferation and ongoing collagen synthesis.

Aminoterminal propeptides of type III procollagen in human cerebrospinal fluid.

The concentrations of aminoterminal propeptides of procollagen type III were determined by radioimmunoassay in the cerebrospinal fluids of 64 patients with various neurological disorders, including 4 infant patients (less than 1 year). In cerebrospinal fluids of adult patients with normal composition (protein, glucose, cell count), adult patients with pathologic composition, and infant patients the peptide levels (mean value +/- S.D.) were 4.07 +/- 1.26 micrograms/l, 8.15 +/- 6.78 micrograms/l, and 56.9 +/- 31.0 micrograms/l, respectively. The concentrations ranged from 1.96 to 265 micrograms/l and were independent of the respective serum propeptide levels. No statistic correlation with other parameters was found. Gel chromatography revealed a high degree of molecular weight heterogeneity, a substantial portion of immunoreactive material was eluted even with the void volume of Sephacryl S 300. Different slopes of radioimmunoinhibition curves indicate heterogenous antigenicity among the propeptides from various patients. Interaction of the propeptides with fibronectin and/or heparin is probably not responsible for the heterogeneity. The diagnostic potential of cerebrospinal fluid propeptide levels for local connective tissue (collagen) turnover remains to be elucidated.