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

Abstract

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 µg/l) compared with controls (median 136.1, range 33.8-169.5 µg/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. I ntraventricular haemorrhage (IVH) occurs in 10-20% of all infants with a birth weight of less than 1000 g. [1][2][3][4][5][6] Development of posthaemorrhagic hydrocephalus (PHHC) is seen in 5% of these patients. [4][5][6][7][8] The underlying pathogenesis of hydrocephalus following IVH is not well understood. However, a correlation of the amount of intraventricular blood with the development of PHHC has been proposed. 4 Local therapies after IVH in neonates, such as fibrinolysis, or steroid application failed to reduce the incidence of shunt dependent PHHC.9-14 From the results one may conclude that, apart from the occlusion of the arachnoid villi by blood clots, a fibroproliferative reaction is involved in the pathogenesis of PHHC. 15 16 Autopsy findings in adult patients with malresorptive hydrocephalus following aneurysmal subarachnoid haemorrhage (SAH) revealed a fibroproliferative reaction in conjunction with arachnoidal fibrosis. 15 It is hypothesised that this ultimately led to malresorption of CSF at the arachnoid villi. 15Local activation of collagen synthesis is suggested to be the major trigger for the fibroproliferative reaction.17 18 In experimental models of SAH, increased concentrations of procollagen propeptides of type I and III collagen in the CSF, and leptomeningeal deposition of collagen I and III have been found. [19][20][21] The fibre forming collagens (types I-III) are synthesised by mesenchymal cells as procollagens. The amount of type I procollagen released into the extracellular fluid is directly related to the amount of type I collagen fibres formed and deposited in the ...

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

“…For example, levels of propeptide of type I procollagen increased in the CSF of PHVD premature neonates when compared to those with hydrocephalus associated with congenital malformation [131]; reflecting increased local type I collagen synthesis and turnover, related to the neuropathological (ECM) fibrotic changes found within arachnoid and meningeal tissues.…”

Vascular Endothelial Growth Factor and Transforming Growth Factor-β1 Are Highly Expressed in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus

“…The development of arachnoidal fibrosis ultimately causes cerebrospinal fluid (CSF) malabsorption (9,10) and thereby increased intracranial pressure (ICP) (11). The activation of extracellular matrix protein biosynthesis, measured as the persisting elevation of the propeptides of type I and III procollagen, was found in the CSF of patients who ultimately developed PHHC 3-4 wk after IVH (12,13). CSF concentrations of proinflammatory IL-6 and antiinflammatory IL-10 were measured to illustrate a possible interference of inflammatory cytokine interaction with the expression of VEGF and TGF-␤1.…”

Biomarkers in Neonatal Posthemorrhagic Hydrocephalus

“…To measure upregulation of extracellular matrix protein synthesis and fibroproliferative reactions in the CSF, Heep et al [17] analyzed the concentrations of procollagen I C-propeptide (PICP) as a marker of activated collagen turnover in premature infants with PHH, all of whom required shunt placement, and control infants with congenital hydrocephalus. Concentrations of PICP were higher in infants with PHH than in controls at all time points measured, but the concentrations were found to decline over time.…”