Abstract
Surfactant proteins (SPs) are a multifunctional group of proteins, responsible for the regulation of rheological properties of body fluids, host defense, and cellular waste clearance. Their concentrations are changed in cerebrospinal fluid (CSF) of patients suffering from communicating hydrocephalus. Hydrocephalic conditions are accompanied by altered CSF flow dynamics; however, the association of CSF-SP concentrations and CSF flow has not yet been investigated. Hence, the aim of this study was to evaluate the association between SP concentrations in the CSF and marked CSF flow phenomena at different anatomical landmarks of CSF spaces. Sixty-one individuals (15 healthy subjects and 46 hydrocephalus patients) were included in this study. CSF specimens were analyzed for SP-A, SP-B, SP-C, and SP-D concentrations by the use of enzyme-linked immunosorbent assays (ELISA). CSF flow was evaluated in axial T2_turbo inversion recovery magnitude (TIRM)-weighted and sagittal T2-weighted magnetic resonance imaging sections using a 4-grade scale (1—no flow, 2—subtle flow, 3—moderate flow, and 4—strong flow). CSF-SP concentrations (mean ± standard deviation) of the overall collective were as follows: SP-A = 0.73 ± 0.58 ng/ml, SP-B = 0.17 ± 0.93 ng/ml, SP-C = 0.95 ± 0.75 ng/ml, and SP-D = 7.43 ± 5.17 ng/ml. The difference between healthy controls and hydrocephalic patients regarding CSF concentrations of SP-A (0.34 ± 0.22 vs. 0.81 ± 0.59 ng/ml) and SP-C (0.48 ± 0.29 vs. 1.10 ± 0.79 ng/ml) revealed to be statistically significant as calculated by means of ANOVA (p values of 0.022 and 0.007, respectively). CSF flow voids were detectable at all investigated landmarks of the CSF spaces (foramina of Monro, third ventricle, mesencephalic aqueduct, prepontine cistern, fourth ventricle, cisterna magna, and craniocervical junction). CSF flow voids, reported as mean ± standard deviation, revealed to be significantly increased in hydrocephalic patients compared to controls as calculated by means of ANOVA (respective p values are given in brackets following values of descriptive statistics) at the following sites: foramina of Monro (1.60 ± 0.91 vs. 2.37 ± 0.99, p = 0.01), fourth ventricle (1.67 ± 0.98 vs. 2.52 ± 1.05, p = 0.007), and the cisterna magna (1.93 ± 1.10 vs. 2.72 ± 1.13, p = 0.022). Spearman’s rank order calculation identified significant correlations for CSF flow voids at the foramina of Monro and the third ventricle with SP-A (r = 0.429, p = 0.001 and r = 0.464, p < 0.001) and CSF flow void at the mesencephalic duct with SP-D (r = − 0.371, p = 0.039). Furthermore, SP-C showed a moderate inverse correlation with age (r = − 0.302, p = 0.022). The present study confirmed statistically significant differences in SP-CSF concentrations between healthy controls and hydrocephalic patients. Additionally, significant correlations between SP concentrations in CSF with increased CSF flow were identified. These findings underline the role of SPs as regulators of CSF rheology.
Similar content being viewed by others
References
Phizackerley PJ, Town MH, Newman GE (1979) Hydrophobic proteins of lamellated osmiophilic bodies isolated from pig lung. Biochem J 183(3):731–736. https://doi.org/10.1042/bj1830731
Palaniyar N (2010) Antibody equivalent molecules of the innate immune system: parallels between innate and adaptive immune proteins. Innate Immun 16(3):131–137. https://doi.org/10.1177/1753425910370498
Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5(1):58–68. https://doi.org/10.1038/nri1528
Hawgood S, Derrick M, Poulain F (1998) Structure and properties of surfactant protein B. Biochim Biophys Acta 1408(2-3):150–160. https://doi.org/10.1016/S0925-4439(98)00064-7
Johansson J (1998) Structure and properties of surfactant protein C. Biochim Biophys Acta 1408(2-3):161–172. https://doi.org/10.1016/S0925-4439(98)00065-9
Schürch D, Ospina OL, Cruz A, Pérez-Gil J (2010) Combined and independent action of proteins SP-B and SP-C in the surface behavior and mechanical stability of pulmonary surfactant films. Biophys J 99(10):3290–3299. https://doi.org/10.1016/j.bpj.2010.09.039
Chroneos ZC, Sever-Chroneos Z, Shepherd VL (2010) Pulmonary surfactant: an immunological perspective. Cell Physiol Biochem 25(001):13–26. https://doi.org/10.1159/000272047
Whitsett JA (2014) The molecular era of surfactant biology. Neonatology 105(4):337–343. https://doi.org/10.1159/000360649
Sardesai S, Biniwale M, Wertheimer F, Garingo A, Ramanathan R (2016) Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future. Pediatr Res 81(1-2):240–248. https://doi.org/10.1038/pr.2016.203
Enhörning G, Robertson B (1972) Lung expansion in the premature rabbit fetus after tracheal deposition of surfactant. Pediatrics 50(1):58–66
Fujiwara T, Maeta H, Chida S, Morita T, Watabe Y, Abe T (1980) Artificial surfactant therapy in hyaline-membrane disease. Lancet 1(8159):55–59
Schicht M, Stengl C, Sel S, Heinemann F, Götz W, Petschelt A, Pelka M, Scholz M et al (2015) The distribution of human surfactant proteins within the oral cavity and their role during infectious diseases of the gingiva. Ann Anat 199:92–97. https://doi.org/10.1016/j.aanat.2014.05.040
Yadav AK, Madan T, Bernal AL (2011) Surfactant proteins A and D in pregnancy and parturition. Front Biosci (Elite Ed) 3:291–300
Beileke S, Claassen H, Wagner W, Matthies C, Ruf C, Hartmann A, Garreis F, Paulsen F et al (2015) Expression and localization of lung surfactant proteins in human testis. PLoS One 10(11):e0143058. https://doi.org/10.1371/journal.pone.0143058.s001
Schob S, Schicht M, Sel S, Stiller D, Kekulé A, Paulsen F, Maronde E, Bräuer L (2013) The detection of surfactant proteins A, B, C and D in the human brain and their regulation in cerebral infarction, autoimmune conditions and infections of the CNS. PLoS One 8(9):e74412. https://doi.org/10.1371/journal.pone.0074412
Schob S, Dieckow J, Fehrenbach M, et al (2016) Occurrence and colocalization of surfactant proteins A, B, C and D in the developing and adult rat brain. Ann Anat:210:121–127. https://doi.org/10.1016/j.aanat.2016.10.006
Schob S, Weiss A, Dieckow J et al (2017) Correlations of ventricular enlargement with rheologically active surfactant proteins in cerebrospinal fluid. Front Aging Neurosci 8:1–4. https://doi.org/10.3389/fnagi.2016.00324
Schob S, Lobsien D, Friedrich B, Bernhard MK, Gebauer C, Dieckow J, Gawlitza M, Pirlich M et al (2016) The cerebral surfactant system and its alteration in hydrocephalic conditions. PLoS One 11(9):e0160680. https://doi.org/10.1371/journal.pone.0160680
Preuss M, Hoffmann KT, Reiss-Zimmermann M, Hirsch W, Merkenschlager A, Meixensberger J, Dengl M (2013) Updated physiology and pathophysiology of CSF circulation—the pulsatile vector theory. Childs Nerv Syst 29(10):1811–1825. https://doi.org/10.1007/s00381-013-2219-0
Simon MJ, Iliff JJ (2016) Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease. Biochim Biophys Acta 1862(3):442–451. https://doi.org/10.1016/j.bbadis.2015.10.014
Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, Benveniste H (2013) Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest 123(3):1299–1309. https://doi.org/10.1172/JCI67677DS1
Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, Singh I, Deane R et al (2014) Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 34(49):16180–16193. https://doi.org/10.1523/JNEUROSCI.3020-14.2014
Kress BT, Iliff JJ, Xia M, Wang M, Wei HS, Zeppenfeld D, Xie L, Kang H et al (2014) Impairment of paravascular clearance pathways in the aging brain. Ann Neurol 76(6):845–861. https://doi.org/10.1002/ana.24271
Bakker ENTP, Bacskai BJ, Arbel-Ornath M, Aldea R, Bedussi B, Morris AWJ, Weller RO, Carare RO (2016) Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases. Cell Mol Neurobiol 36(2):181–194. https://doi.org/10.1007/s10571-015-0273-8
Morris AWJ, Sharp MM, Albargothy NJ et al (2016) Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathol 131(5):725–736. https://doi.org/10.1007/s00401-016-1555-z
Bradley WG Jr (2015) CSF flow in the brain in the context of normal pressure hydrocephalus. AJNR 36(5):831–838. https://doi.org/10.3174/ajnr.A4124
Tarnaris A, Toma AK, Pullen E, Chapman MD, Petzold A, Cipolotti L, Kitchen ND, Keir G et al (2011) Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus. Alzheimers Dement 7(5):501–508. https://doi.org/10.1016/j.jalz.2011.01.003
Ray B, Reyes PF, Lahiri DK (2011) Biochemical studies in normal pressure hydrocephalus (NPH) patients: change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Aß) peptide and phospho-tau. J Psychiatr Res 45(4):539–547. https://doi.org/10.1016/j.jpsychires.2010.07.011
Rodis I, Mahr CV, Fehrenbach MK, Meixensberger J, Merkenschlager A, Bernhard MK, Schob S, Thome U et al (2016) Hydrocephalus in aqueductal stenosis—a retrospective outcome analysis and proposal of subtype classification. Childs Nerv Syst 32(4):617–627. https://doi.org/10.1007/s00381-016-3029-y
Mahr CV, Dengl M, Nestler U, Reiss-Zimmermann M, Eichner G, Preuß M, Meixensberger J (2016) Idiopathic normal pressure hydrocephalus: diagnostic and predictive value of clinical testing, lumbar drainage, and CSF dynamics. J Neurosurg 125(3):591–597. https://doi.org/10.3171/2015.8.JNS151112
Lieb JM, Stippich C, Ahlhelm FJ (2015) Normal pressure hydrocephalus. Radiologe 55(5):389–396. https://doi.org/10.1007/s00117-014-2797-1
Freeman WD (2015) Raised intracranial pressure. In: Demaerschalk BM, Wingerchuk DM (eds) Evidence-based neurology: management of neurological disorders. John Wiley & Sons, Ltd, Chichester
Lisanti C, Carlin C, Banks KP, Wang D (2007) Normal MRI appearance and motion-related phenomena of CSF. AJR Am J Roentgenol 188(3):716–725. https://doi.org/10.2214/AJR.05.0003
Simonson TM, Magnotta VA, Ehrhardt JC, Crosby DL, Fisher DJ, Yuh WT (1996) Echo-planar FLAIR imaging in evaluation of intracranial lesions. Radiographics 16(3):575–584. https://doi.org/10.1148/radiographics.16.3.8897625
Von Schulthess GK, Higgins CB (1985) Blood flow imaging with MR: spin-phase phenomena. Radiology 157(3):687–695. https://doi.org/10.1148/radiology.157.3.2997836
Sherman JL, Citrin CM (1986) Magnetic resonance demonstration of normal CSF flow. AJNR 7(1):3–6
Nayak A, Dodagatta-Marri E, Tsolaki AG, Kishore U (2012) An insight into the diverse roles of surfactant proteins, SP-A and SP-D in innate and adaptive immunity. Front Immunol 3:131. https://doi.org/10.3389/fimmu.2012.00131
Wolburg H, Paulus W (2009) Choroid plexus: biology and pathology. Acta Neuropathol 119(1):75–88. https://doi.org/10.1007/s00401-009-0627-8
Sunde M, Pham CLL, Kwan AH (2016) Molecular characteristics and biological functions of surface-active and surfactant proteins. Annu Rev Biochem 86(1):585–608. https://doi.org/10.1146/annurev-biochem-061516-044847
Willander H, Presto J, Askarieh G (2012) BRICHOS domains efficiently delay fibrillation of amyloid β-peptide. J Biol Chem 287(37):31608–31617. https://doi.org/10.1074/jbc.M112.393157
Landreh M, Rising A, Presto J, Jörnvall H, Johansson J (2015) Specific chaperones and regulatory domains in control of amyloid formation. J Biol Chem 290(44):26430–26436. https://doi.org/10.1074/jbc.R115.653097
Le Bihan D, Breton E, Lallemand D, Grenier P (1986) MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161(2):401–407. https://doi.org/10.1148/radiology.161.2.3763909
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study with retrospective design was approved by an institutional review board (Ethikkommission Universität Leipzig Az 330-13-18112013). Informed consent for the scientific use of CSF samples and clinical and radiological data were obtained in writing.
Rights and permissions
About this article
Cite this article
Schob, S., Weiß, A., Surov, A. et al. Elevated Surfactant Protein Levels and Increased Flow of Cerebrospinal Fluid in Cranial Magnetic Resonance Imaging. Mol Neurobiol 55, 6227–6236 (2018). https://doi.org/10.1007/s12035-017-0835-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-017-0835-5