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Hypercapnia is a Possible Determinant of the Function of the Blood-Cerebrospinal Fluid Barrier in Amyotrophic Lateral Sclerosis

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Abstract

Elevated cerebrospinal fluid (CSF)/serum quotients of albumin (QAlb) may occur in motor neuron diseases (MND) including amyotrophic lateral sclerosis (ALS), but the pathophysiologic mechanisms underlying these alterations are unclear. Evidence from animal experiments suggests that the arterial carbon dioxide level might affect the QAlb, i.e. the function of the blood-CSF barrier (BCB). We therefore compared basic CSF parameters in different forms of MND (ALS, n = 105; lower motor neuron diseases, n = 12; and upper motor neuron diseases, n = 7) and investigated the relationship between elevated QAlb and the arterial partial pressure of carbon dioxide (pCO2) in ALS where respiratory insufficiency leads to hypercapnia in the course of the disease. Pathologic elevations of QAlb occurred in 32 of 124 MND patients. In ALS, QAlb significantly correlated with the arterial pCO2 (r = 0.454; P = 0.001; n = 45). These data indicate that BCB dysfunction is a frequent finding in different forms of MND and may reflect distinct pathophysiological mechanisms. In ALS, an important underlying mechanism might be the influence of the arterial pCO2 which may alter the CSF flow.

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References

  1. Reiber H (1994) Flow rate of cerebrospinal fluid (CSF)—a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122:189–203

    Article  CAS  PubMed  Google Scholar 

  2. Tibbling G, Link H, Ohman S (1977) Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 37:385–390

    CAS  PubMed  Google Scholar 

  3. Brettschneider J, Claus A, Kassubek J et al (2005) Isolated blood-cerebrospinal fluid barrier dysfunction: prevalence and associated diseases. J Neurol 252:1067–1073

    Article  CAS  PubMed  Google Scholar 

  4. Banks WA (1999) Physiology and pathology of the blood-brain barrier: implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. J Neurovirol 5:538–555

    Article  CAS  PubMed  Google Scholar 

  5. Seyfert S, Kunzmann V, Schwertfeger N et al (2002) Determinants of lumbar CSF protein concentration. J Neurol 249:1021–1026

    Article  CAS  PubMed  Google Scholar 

  6. Leonardi A, Abbruzzese G, Arata L et al (1984) Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis. J Neurol 231:75–78

    Article  CAS  PubMed  Google Scholar 

  7. Apostolski S, Nikolic J, Bugarski-Prokopljevic C et al (1991) Serum and CSF immunological findings in ALS. Acta Neurol Scand 83:96–98

    Article  CAS  PubMed  Google Scholar 

  8. Habgood MD (1995) The nature of increased blood-cerebrospinal fluid barrier exchange during CO2 inhalation in newborn and adult rats. Exp Physiol 80:117–128

    CAS  PubMed  Google Scholar 

  9. Cutler RW, Barlow CF (1966) The effect of hypercapnia on brain permeability to protein. Arch Neurol 14:54–63

    CAS  PubMed  Google Scholar 

  10. Sussmuth SD, Brettschneider J, Ludolph AC et al (2008) Biochemical markers in CSF of ALS patients. Curr Med Chem 15:1788–1801

    Article  PubMed  Google Scholar 

  11. Brooks BR, Miller RG, Swash M et al (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299

    Article  CAS  PubMed  Google Scholar 

  12. Van den Berg-Vos RM, Visser J, Franssen H et al (2003) Sporadic lower motor neuron disease with adult onset: classification of subtypes. Brain 126:1036–1047

    Article  PubMed  Google Scholar 

  13. Pringle CE, Hudson AJ, Munoz DG et al (1992) Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria. Brain 115(Pt 2):495–520

    Article  PubMed  Google Scholar 

  14. Strong MJ, Gordon PH (2005) Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: discrete entities or spectrum? Amyotroph. Lateral Scler Other Motor Neuron Disord 6:8–16

    Article  Google Scholar 

  15. Le Forestier N, Maisonobe T, Spelle L et al (2001) Primary lateral sclerosis: further clarification. J Neurol Sci 185:95–100

    Article  CAS  PubMed  Google Scholar 

  16. Evans CA, Reynolds JM, Reynolds ML et al (1976) The effect of hypercapnia on a blood-brain barrier mechanism in foetal and new-born sheep. J Physiol 255:701–714

    CAS  PubMed  Google Scholar 

  17. Garbuzova-Davis S, Saporta S, Haller E et al (2007) Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS. PLoS ONE 2:e1205

    Article  PubMed  Google Scholar 

  18. Zhong Z, Deane R, Ali Z et al (2008) ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 11:420–422

    Article  CAS  PubMed  Google Scholar 

  19. Janssen JC, Godbolt AK, Ioannidis P et al (2004) The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia. J Neurol 251:184–188

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Refika Aksamija, Vera Lehmensiek, Christa Ondratscheck, and Dagmar Vogel for skillful laboratory work.

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Authors and Affiliations

  1. Department of Neurology, Neurologische Klinik der Universität Ulm, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany

    Sigurd D. Süssmuth, Anne D. Sperfeld, Albert C. Ludolph & Hayrettin Tumani

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  1. Sigurd D. Süssmuth
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  2. Anne D. Sperfeld
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  3. Albert C. Ludolph
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  4. Hayrettin Tumani
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Correspondence to Sigurd D. Süssmuth.

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Süssmuth, S.D., Sperfeld, A.D., Ludolph, A.C. et al. Hypercapnia is a Possible Determinant of the Function of the Blood-Cerebrospinal Fluid Barrier in Amyotrophic Lateral Sclerosis. Neurochem Res 35, 1071–1074 (2010). https://doi.org/10.1007/s11064-010-0156-9

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  • DOI: https://doi.org/10.1007/s11064-010-0156-9

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