Skip to main content
SpringerLink
Log in

Pathophysiologic characteristics of balloon cells in cortical dysplasia

  • Original Paper
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Objects

Balloon cells are histopathological hallmarks of cortical malformations, i.e., focal cortical dysplasia (FCD) of the Taylor type or the cortical tubers of tuberous sclerosis, and they are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. This study was carried out to investigate the developmental histogenesis and epileptogenesis of balloon cells in FCD.

Materials and methods

We used an immunohistochemical approach to examine the expressions of primitive neuroepithelial cell antigens (CD34, nestin, and vimentin), ionotrophic glutamate receptor subunits (NR1, NR2A/B, GluR1, GluR2, GluR3, GluR4, and GluR5/6/7), and P-glycoprotein in balloon cells from FCD and normal cerebral cortex epileptogenic lesions.

Conclusion

Balloon cells presented in clusters or as scattered cells throughout FCD lesions involving the gray and white matter. We found the balloon cells to be classifiable into three subtypes based on glial fibrillary acidic protein (GFAP) and neurofilament protein (NF-L) immunohistochemistry, i.e., as neuronal, astrocytic, and uncommitted. Immunopositivity for nestin, CD34, and vimentin in balloon cells of FCD suggests that they may be derived from the abnormal development and differentiation of neural stem cells. Moreover, it appears that epileptogenesis in cortical dysplasia is partly caused by the upregulations of some glutamate receptor subunit proteins (NR1, NR2A/B, GluR1, and GluR3) in balloon cells and dysplastic neurons. We speculate that the presence of the drug resistance protein P-glycoprotein in balloon cells might explain medically refractory epilepsy in FCD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Arai N, Oda M (1997) Surgical neuropathology of intractable epilepsy. Epilepsia 38:11–16

    Article  Google Scholar 

  2. Armstrong DD, Bruton CJ (1987) Postscript: what terminology is appropriate for tissue pathology? How dose it predict outcome? In: Emgel J Jr Surgical treatment of the epilepsies 2nd edn. NewYork, Raven, pp 49–63

    Google Scholar 

  3. Aronica E, Gorter JA, Jansen GH, van Veelen CW, van Rijen PC, Leenstra S, Ramkema M, Scheffer GL, Scheper RJ, Troost D (2003) Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors. Neuroscience 118:417–429

    Article  PubMed  CAS  Google Scholar 

  4. Barkovich AJ, Kjos BO (1992) Gray matter heterotopias: MR characteristics and correlation with developmental and neurologic manifestations. Radiology 182:493–499

    PubMed  CAS  Google Scholar 

  5. Barkovich AJ, Kuzniecky RI, Dobyns WB, Jackson GD, Becker LE, Evard P (1996) A classification scheme for malformations of cortical development. Neuropediatrics 27:59–63

    Article  PubMed  CAS  Google Scholar 

  6. Barkovich AJ, Raybaud CA (2004) Neuroimaging in disorders of cortical development. Neuroimaging Clin N Am 14:231–254

    Article  PubMed  Google Scholar 

  7. Barth PG (1987) Disorders of neuronal migration. Can J Neurol Sci 14:1–16

    PubMed  CAS  Google Scholar 

  8. Blumcke I, Wiestler OD (2002) Gangliogliomas: an intriguing tumor entity associated with focal epilepsies. J Neuropathol Exp Neurol 61:575–584

    PubMed  Google Scholar 

  9. Farrel MA, DeRosa MJ, Curran JG, Secor DL, Cornford ME, Comair YG, Peacock WJ, Shields WD, Vinters HV (1992) Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy. Acta Neuropathol Berl 83:246–259

    Article  Google Scholar 

  10. Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, Sutherland DR, Baker MA, Greaves MF (1990) Expression of the CD34 gene in vascular endothelial cells. Blood 15(75):2417–2426

    Google Scholar 

  11. Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108

    Article  Google Scholar 

  12. Kalman M, Ajtai BM (2001) A comparison of intermediate filament markers for presumptive astroglia in the developing rat neocortex: immunostaining against nestin reveals more detail, than GFAP or vimentin. Int J Dev Neurosci 19:101–108

    Article  PubMed  CAS  Google Scholar 

  13. Kilty IC, Barraclough R, Schmidt G, Rudland PS (1999) Isolation of a potential neural stem cell line from the internal capsule of an adult transgenic rat brain. J Neurochem 73:1859–1870

    PubMed  CAS  Google Scholar 

  14. Krause DS, Fackler MJ, Civin CI, May WS (1996) CD34: structure, biology, and clinical utility. Blood 87:1–13

    PubMed  CAS  Google Scholar 

  15. Kuzniecky RI, Barkovich AJ (1996) Pathogenesis and pathology of focal malformations of cortical development and epilepsy. J Clin Neurophysiol 13:468–480

    Article  PubMed  CAS  Google Scholar 

  16. Kuzniecky RI, Knowlton RC (2002) Neuroimaging of epilepsy. Semin Neurol 22:279–288

    Article  PubMed  Google Scholar 

  17. Lanza F, Healy L, Sutherland DR (2001) Structural and functional features of the CD34 antigen: an update. J Biol Regul Homeost Agents 15:1–13

    PubMed  CAS  Google Scholar 

  18. Lazarowski A, Sevlever G, Taratuto A, Massaro M, Rabinowicz A (1999) Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy. Pediatr Neurol 21:731–734

    Article  PubMed  CAS  Google Scholar 

  19. Lee MC, Kim KM, Woo YJ, Kim MK, Kim JH, Nam SC, Suh JJ, Chung WK, Lee JS, Kim HI, Choi HY, Kim SU (2001) Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy. Human Pathol 32:643–648

    Article  CAS  Google Scholar 

  20. Lee MC, Lee JS, Lee MJ, Lee JH, Kim HI (2001) Fas mediates apoptosis in steroid-induced myopathy of rats. Neuropathol Appl Neurobiol 27:396–402

    Article  Google Scholar 

  21. Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 23(60):585–595

    Article  Google Scholar 

  22. Lin G, Finger E, Gutierrez-Ramos JC (1995) Expression of CD34 in endothelial cells, hematopoietic progenitors and nervous cells in fetal and adult mouse tissues. Eur J Immunol 25:1508–1516

    Article  PubMed  CAS  Google Scholar 

  23. Lukas Z, Draber P, Bucek J, Draberova E, Viklicky V, Staskova Z (1989) Expression of vimentin and glial fibrillary acidic protein in human developing spinal cord. Histochem J 21:693–701

    Article  PubMed  CAS  Google Scholar 

  24. Meencke HJ, Janz D (1984) Neuropathological findings in primary generalized epilepsy: a study of eight cases. Epilepsia 25:8–21

    Article  PubMed  CAS  Google Scholar 

  25. Meguro H, Mori H, Araki K, Kushiya E, Kutsuwada T, Yamazaki M, Kumanishi T, Arakawa M, Sakimura K, Mishina M (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357:70–74

    Article  PubMed  CAS  Google Scholar 

  26. Meldrum BS, Akbar MT, Chapman AG (1999) Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res 36:189–204

    Article  PubMed  CAS  Google Scholar 

  27. Mischel PS, Nguyen LP, Vinters HV (1995) Cerebral cortical dysplasia associated with pediatric epilepsy: Review of neuropathologic features and proposal for grading system. J Neuropathol Exp Neurol 54:137–153

    PubMed  CAS  Google Scholar 

  28. Mizoguchi M, Iwaki T, Morioka T, Fukui M, Tateishi J (1998) Abnormal cytoarchitecture of cortical dysplasia verified by immunohistochemistry. Clin Neuropathol 17:100–109

    PubMed  CAS  Google Scholar 

  29. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217–1221

    Article  PubMed  CAS  Google Scholar 

  30. Nakanishi S, Masu M (1994) Molecular diversity and functions of glutamate receptors. Ann Rev Biophy Biomol Struct 23:319–348

    Article  CAS  Google Scholar 

  31. Natkunam Y, Rouse RV, Zhu S, Fisher C, van De Rijn M (2000) Immunoblot analysis of CD34 expression in histologically diverse neoplasms. Am J Pathol 156:21–27

    PubMed  CAS  Google Scholar 

  32. Pasquier B, Peoc’ h M, Fabre-Bocquentin B, Bensaadi L, Pasquier D, Hoffmann D, Kahane P, Tassi L, Le Bas JF, Benabid AL (2002) Surgical pathology of drug-resistant partial epilepsy. A 10-year-experience with a series of 327 consecutive resections. Epileptic Disord 4:99–119

    PubMed  Google Scholar 

  33. Plate KH, Wieser HG, Yasargil MG, Wiestler OD (1993) Neuropathological findings in 224 patients with temporal lobe epilepsy. Acta Neuropathol Berl 86:433–438

    Article  PubMed  CAS  Google Scholar 

  34. Ploemacher RE (1999) Characterization and biology of normal human haematopoietic stem cells. Haematologica 84(Suppl EHA 4):4–7

    PubMed  Google Scholar 

  35. Prayson RA, Frater JL (2003) Cortical dysplasia in extratemporal lobe intractable epilepsy: a study of 52 cases. Ann Diagn Pathol 7:139–146

    Article  PubMed  Google Scholar 

  36. Raymond AA, Fish DR, Sisodiya SM, Alsanjari N, Stevens JM, Shorvon SD (1995) Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia, microdysgenesis, dysembryoplastic neuroepithelial tumour and dysgenesis of the archicortex in epilepsy. Clinical, EEG, and neuroimaging features in 100 adult patients. Brain 118:629–660

    Article  PubMed  Google Scholar 

  37. Reifenberger G, Weber T, Weber RG, Wolter M, Brandis A, Kuchelmeister K, Pilz P, Reusche E, Lichter P, Wiestler OD (1999) Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity. Brain Pathol 9:617–626

    Article  PubMed  CAS  Google Scholar 

  38. Reifenberger G, Kaulich K, Wiestler OD, Blumcke I (2003) Expression of the CD34 antigen in pleomorphic xanthoastrocytomas. Acta Neuropathol (Berl) 105:358–364

    CAS  Google Scholar 

  39. Rizz M, Caccia S, Guiso G, Richichi C, Gorter JA, Aronica E, Alipran DM, Bagnati R, Fanelli R, D'incalci M, Samanin R, Vezzani A (2002) Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistence. J Neurosci 22:5883–5839

    Google Scholar 

  40. Schinkel AH, Wagenaar E, Mol CA, Van Deemter L (1996) P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 97:2517–2524

    PubMed  CAS  Google Scholar 

  41. Sisodiya SM, Heffernan J, Squier MV (1999) Overexpression of P-glycoprotein in malformations of cortical development. Neuroreport 10:3437–3441

    Article  PubMed  CAS  Google Scholar 

  42. Sisodiya SM, Lin WR, Harding BN, Squier MV, Thom M (2002) Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 125:22–31

    Article  PubMed  CAS  Google Scholar 

  43. Steen R, Egeland T (1998) CD34 molecule epitope distribution on cells of haematopoietic origin. Leuk Lymphoma 30:23–30

    PubMed  CAS  Google Scholar 

  44. Steward VW, Jevtic MM (1979) Derangement of neuronal migration in a child with multiple congenital anomalies, two congenital neoplasms, without apparent chromosomal abnormalities. J Neuropathol Exp Neurol 38:259–285

    Article  PubMed  CAS  Google Scholar 

  45. Sutherland DR, Keating A (1992) The CD34 antigen: structure, biology, and potential clinical applications. J Hematother 1:115–129

    PubMed  CAS  Google Scholar 

  46. Taylor DC, Falconer MA, Bruton CJ, Corsellis JAN (1971) Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiat 34:369–387

    Article  PubMed  CAS  Google Scholar 

  47. Wong RK, Bianchi R, Taylor GW, Merlin LR (1999) Role of metabotropic glutamate receptors in epilepsy. Adv Neurol 79:685–698

    PubMed  CAS  Google Scholar 

  48. Wood HB, May G, Healy L, Enver T, Morriss-Kay GM (1997) CD34 expression patterns during early mouse development are related to modes of blood vessel formation and reveal additional sites of hematopoiesis. Blood 15:2300–2311

    Google Scholar 

  49. Yabe JT, Chan WK, Wang FS, Pimenta A, Ortiz DD, Shea TB (2003) Regulation of the transition from vimentin to neurofilaments during neuronal differentiation. Cell Motil Cytoskeleton 56:193–205

    Article  PubMed  CAS  Google Scholar 

  50. Zhong Y, Thomas LB, Youssef GC, William B, Michael B, Kathy T (1998) Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice variants in dysplastic neurons of human epileptic neocortex. J Neuropathol Exp Neurol 57:47–62

    Google Scholar 

Download references

Acknowledgment

This study was financially supported by the Brain Disease Research Center of KOSEF in Ajou University, Suwon, Korea.

Author information

Authors and Affiliations

  1. Department of Pathology, Chonnam National University Medical School and Center for Biomedical Human Resources (BK-21), 5 Hakdong, Dongku, Gwangju, 501-746, Korea

    Hyun-Sik Oh, Min-Cheol Lee, Hyung-Seok Kim, Ji-Shin Lee & Jae-Hyuk Lee

  2. Department of Neurology, Chonnam National University Medical School, Gwangju, Korea

    Myeong-Kyu Kim

  3. Department of Pediatrics, Chonnam National University Medical School, Gwangju, Korea

    Young-Jong Woo

  4. Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Korea

    Jae-Hyoo Kim

  5. Department of Neurosurgery, Jesus Hospital, Chunju, Korea

    Hyoung-Ihl Kim

  6. Brain Disease Research Center, Ajou University, Suwon, Korea

    Seung-Up Kim

  7. Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    Seung-Up Kim

Authors
  1. Hyun-Sik Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min-Cheol Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyung-Seok Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ji-Shin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jae-Hyuk Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Myeong-Kyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Young-Jong Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jae-Hyoo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hyoung-Ihl Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Seung-Up Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Min-Cheol Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, HS., Lee, MC., Kim, HS. et al. Pathophysiologic characteristics of balloon cells in cortical dysplasia. Childs Nerv Syst 24, 175–183 (2008). https://doi.org/10.1007/s00381-007-0453-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-007-0453-z

Keywords

Search

Navigation