Accumulation of Transforming Growth Factor-β&lt;sub&gt;2&lt;/sub&gt; and Nitrated Chondroitin Sulfate Proteoglycans in Cerebrospinal Fluid Correlates with Poor Neurologic Outcome in Preterm Hydrocephalus

Chow, Lily C.; Soliman, Antoine; Zandian, Mandana; Danielpour, Moise; Krueger, Richard C.

doi:10.1159/000083945

Cited by 31 publications

(11 citation statements)

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“…18,94 In support of this hypothesis, one study found a correlation between abnormal levels of TGF-β2 and extracellular matrix proteins (chondroitin sulfate proteoglycan) and the development of symptomatic PHH in preterm infants (in contrast to pre-term infants without PHH). 20 In an animal model of IVH, drugs that inhibit TGF-β2 were ineffective in controlling hydrocephalus. 2 In another human study of biomarkers specifcally implicated in impaired CSF absorption, the levels of TGF-β1 and aminoterminal propeptide of Type I collagen (PC1NP) were studied in neonates with symptomatic PHH, hydrocephalus from open spina bifida, and aqueductal stenosis.…”

Section: Resultsmentioning

confidence: 99%

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

Robinson

2012

PED

232

214

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Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identified in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is essential because of the declining incidence of IVH and PHH, variations in referral patterns, and neonatal ICU and neurosurgical management. Well-designed multicenter trials will eventually produce evidence to enable neurosurgeons to provide their smallest, most vulnerable patients with the best practices to minimize perioperative complications and permanent shunt dependence, and most importantly, optimize long-term neurodevelopmental outcomes.

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Section: Resultsmentioning

confidence: 99%

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

Robinson

2012

PED

232

214

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“…Clinically, high protein levels in the CSF have been detected in hydrocephalus irrespective of radiologic obstruction to the CSF pathways. Higher levels of thrombopoietin [34], ferritin [35], nerve growth factor[36], chondroitin sulfate proteoglycan [37] transforming growth factor β1 [38,39], transforming growth factor β2 [37], S-100 protein [40,41], and vascular endothelial growth factor [42] have been found in ventricular CSF in patients with hydrocephalus resulting from intraventricular hemorrhage. Even in patients without any intraventricular blood, elevated proteins have been found in ventricular CSF in hydrocephalus resulting from intracranial schwannomas [7], a few cases of spinal schwannomas [8,9], and in about 4% of patients with Guillain-Barre' syndrome [10,11].…”

Section: Discussionmentioning

confidence: 99%

Intraventricular infusion of hyperosmolar dextran induces hydrocephalus: a novel animal model of hydrocephalus

Krishnamurthy

Schultz

et al. 2009

Fluids Barriers CNS

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BackgroundPopular circulation theory of hydrocephalus assumes that the brain is impermeable to cerebrospinal fluid (CSF), and is therefore incapable of absorbing the CSF accumulating within the ventricles. However, the brain parenchyma is permeable to water due to the presence of specific ion channels as well as aquaporin channels. Thus, the movement of water into and out of the ventricles may be determined by the osmotic load of the CSF. If osmotic load determines the aqueous content of CSF in this manner, it is reasonable to hypothesize that hydrocephalus may be precipitated by pathologies and/or insults that produce sustained elevations of osmotic content within the ventricles.MethodsWe investigated this hypothesis by manipulating the osmotic content of CSF and assaying the development of hydrocephalus in the rat brain. This was achieved by continuously infusing artificial CSF (negative control; group I), fibroblast growth factor (FGF2) solution (positive control; group II) and hyperosmotic dextran solutions (10 KD and 40 KD as experimental solutions: groups III and IV) for 12 days at 0.5 μL/h. The osmolality of the fluid infused was 307, 664, 337 and 328 mOsm/L in Groups I, II, III and IV, respectively. Magnetic resonance imaging (MRI) was used to evaluate the ventricular volumes. Analysis of variance (ANOVA) with pairwise group comparisons was done to assess the differences in ventricular volumes among the four groups.ResultsGroup I had no hydrocephalus. Group II, group III and group IV animals exhibited significant enlargement of the ventricles (hydrocephalus) compared to group I. There was no statistically significant difference in the size of the ventricles between groups II, III and IV. None of the animals with hydrocephalus had obstruction of the aqueduct or other parts of CSF pathways on MRI.ConclusionInfusing hyperosmolar solutions of dextran, or FGF into the ventricles chronically, resulted in ventricular enlargement. These solutions increase the osmotic load in the ventricles. Water influx (through the choroid plexus CSF secretion and/or through the brain) into the ventricles to normalize this osmotic gradient results in hydrocephalus. We need to revise the popular theory of how fluid accumulates in the ventricles at least in some forms of hydrocephalus.

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“…Clinically, high levels of proteins such as thrombopoietin (17), ferritin (18), nerve growth factor (19), chondroitin sulfate proteoglycan (20), transforming growth factor beta 1 (21,22), transforming growth factor beta 2 (20), S-100 protein (23,24), glial fibrillary acidic protein (GFAP) (24), neuron specific enolase (NSE) (24), myelin basic protein (MBP) (24), and vascular endothelial growth factor (25) within ventricular CSF, which may contribute to an elevation in osmolarity, have been observed in patients with hydrocephalus. Additionally, it has been shown that brain edema results from hyponatremia, which is evidence that there is free movement of water from the plasma into the brain tissue (26).…”

Section: Osmotic Gradient and Its Role In Hydrocephalusmentioning

confidence: 99%

A proposed role for efflux transporters in the pathogenesis of hydrocephalus

et al. 2014

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Hydrocephalus is a common brain disorder that is treated only with surgery. The basis for surgical treatment rests on the circulation theory. However, clinical and experimental data to substantiate circulation theory have remained inconclusive. In brain tissue and in the ventricles, we see that osmotic gradients drive water diffusion in water-permeable tissue. As the osmolarity of ventricular CSF increases within the cerebral ventricles, water movement into the ventricles increases and causes hydrocephalus. Macromolecular clearance from the ventricles is a mechanism to establish the normal CSF osmolarity, and therefore ventricular volume. Efflux transporters, (p-glycoprotein), are located along the blood brain barrier and play an important role in the clearance of macromolecules (endobiotics and xenobiotics) from the brain to the blood. There is clinical and experimental data to show that macromolecules are cleared out of the brain in normal and hydrocephalic brains. This article summarizes the existing evidence to support the role of efflux transporters in the pathogenesis of hydrocephalus. The location of p-gp along the pathways of macromolecular clearance and the broad substrate specificity of this abundant transporter to a variety of different macromolecules are reviewed. Involvement of p-gp in the transport of amyloid beta in Alzheimer disease and its relation to normal pressure hydrocephalus is reviewed. Finally, individual variability of p-gp expression might explain the variability in the development of hydrocephalus following intraventricular hemorrhage.

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Accumulation of Transforming Growth Factor-β<sub>2</sub> and Nitrated Chondroitin Sulfate Proteoglycans in Cerebrospinal Fluid Correlates with Poor Neurologic Outcome in Preterm Hydrocephalus

Cited by 31 publications

References 93 publications

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

Intraventricular infusion of hyperosmolar dextran induces hydrocephalus: a novel animal model of hydrocephalus

A proposed role for efflux transporters in the pathogenesis of hydrocephalus

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