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Microsurgical removal of intramedullary spinal cord gliomas in a rat spinal cord decreases onset to paresis, an animal model for intramedullary tumor treatment

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Abstract

Objective

Intramedullary spinal cord tumors (IMSCT) pose significant challenges given their recurrence rate and limited treatment options. Using our previously described rat model of IMSCT, we describe a technique for microsurgical tumor resection and present the functional and histopathological analysis of tumor progression.

Methods

Twenty-four Fischer 344 rats were randomized into two groups. All animals received a 5-μl intramedullary injection of 9L gliosarcoma cells. Animals were evaluated daily for signs of paralysis using the Basso, Beattie, and Bresnahan (BBB) scale. Group 1 continued with daily assessments using the BBB scale following tumor implantation, but received no further treatment. Group 2 underwent surgical removal of intramedullary tumor on postoperative day five. At a BBB score less than 5 (e.g., functional paraplegia), all animals of both groups were killed and sent for histopathological analysis.

Results

Group 1 had a median onset of functional hind limb paraplegia at 15 ± 1.0 days. Group 2 had a median onset of hind limb paresis at 53 ± 0.46 days. Hematoxylin–eosin cross-sections confirmed the presence of intramedullary 9L tumor invading the spinal cord in both groups.

Conclusion

Animals with 9L IMSCTs consistently developed hind limb paraplegia in a reliable and reproducible manner. Animals undergoing microsurgical resection of IMSCT had a significant delay in the onset of functional paraplegia compared to the untreated controls. These findings suggest that this model may mimic the behavior of IMSCTs following operative resection in humans and thus may be used to examine efficacy of new treatment options for high-grade intramedullary tumors.

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References

  1. Allen JC, Aviner S, Yates AJ, Boyett JM, Cherlow JM, Turski PA, Epstein F, Finlay JL, Children’s Cancer Group (1998) Treatment of high-grade spinal cord astrocytoma of childhood with “8-in-1” chemotherapy and radiotherapy: a pilot study of CCG-945. J Neurosurg 88:215–220

    PubMed  CAS  Google Scholar 

  2. Balmaceda C (2000) Chemotherapy for intramedullary spinal cord tumors. J Neurooncol 47:293–307

    Article  PubMed  CAS  Google Scholar 

  3. Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244–256

    Article  PubMed  CAS  Google Scholar 

  4. Bouffet E, Amat D, Devaux Y, Desuzinges C (1997) Chemotherapy for spinal cord astrocytoma. Med Pediatr Oncol 29:560–562

    Article  PubMed  CAS  Google Scholar 

  5. Bowers DC, Weprin BE (2003) Intramedullary spinal cord tumors. Curr Treat Options Neurol 5:207–212

    Article  PubMed  Google Scholar 

  6. Caplan J, Pradilla G, Hdeib A, Tyler BM, Legnani FG, Bagley CA, Brem H, Jallo G (2006) A novel model of intramedullary spinal cord tumors in rats: functional progression and histopathological characterization. Neurosurgery 59:193–200 discussion 193–200, 2006

    Article  PubMed  Google Scholar 

  7. Cohen AR, Wisoff JH, Allen JC, Epstein F (1989) Malignant astrocytomas of the spinal cord. J Neurosurg 70:50–54

    PubMed  CAS  Google Scholar 

  8. Constantini S, Houten J, Miller DC, Freed D, Ozek MM, Rorke LB, Allen JC, Epstein FJ (1996) Intramedullary spinal cord tumors in children under the age of 3 years. J Neurosurg 85:1036–1043

    Article  PubMed  CAS  Google Scholar 

  9. Constantini S, Miller DC, Allen JC, Rorke LB, Freed D, Epstein FJ (2000) Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults. J Neurosurg 93:183–193

    PubMed  CAS  Google Scholar 

  10. Cooper PR, Epstein F (1985) Radical resection of intramedullary spinal cord tumors in adults. Recent experience in 29 patients. J Neurosurg 63:492–499

    PubMed  CAS  Google Scholar 

  11. DiMeco F, Rhines LD, Hanes J, Tyler BM, Brat D, Torchiana E, Guarnieri M, Colombo MP, Pardoll DM, Finocchiaro G, Brem H, Olivi A (2000) Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats. J Neurosurg 92:419–427

    Article  PubMed  CAS  Google Scholar 

  12. Epstein FJ, Farmer JP, Freed D (1992) Adult intramedullary astrocytomas of the spinal cord. J Neurosurg 77:355–359

    PubMed  CAS  Google Scholar 

  13. Epstein FJ, Farmer JP, Freed D (1993) Adult intramedullary spinal cord ependymomas: the result of surgery in 38 patients. J Neurosurg 79:204–209

    Article  PubMed  CAS  Google Scholar 

  14. Foreman NK, Hay TC, Handler M (1998) Chemotherapy for spinal cord astrocytoma. Med Pediatr Oncol 30:311–312

    Article  PubMed  CAS  Google Scholar 

  15. Hassall TE, Mitchell AE, Ashley DM (2001) Carboplatin chemotherapy for progressive intramedullary spinal cord low-grade gliomas in children: three case studies and a review of the literature. Neuro Oncol 3:251–257

    Article  PubMed  CAS  Google Scholar 

  16. Isaacson SR (2000) Radiation therapy and the management of intramedullary spinal cord tumors. J Neurooncol 47:231–238

    Article  PubMed  CAS  Google Scholar 

  17. Jallo GI, Danish S, Velasquez L, Epstein F (2001) Intramedullary low-grade astrocytomas: long-term outcome following radical surgery. J Neurooncol 53:61–66

    Article  PubMed  CAS  Google Scholar 

  18. Jallo GI, Freed D, Epstein F (2003) Intramedullary spinal cord tumors in children. Childs Nerv Syst 19:641–649

    Article  PubMed  Google Scholar 

  19. Jallo GI, Volkov A, Wong C, Carson BS Sr., Penno MB (2006) A novel brainstem tumor model: functional and histopathological characterization. Childs Nerv Syst 22:1519–1525

    Article  PubMed  Google Scholar 

  20. Judy KD, Olivi A, Buahin KG, Domb A, Epstein JI, Colvin OM, Brem H (1995) Effectiveness of controlled release of a cyclophosphamide derivative with polymers against rat gliomas. J Neurosurg 82:481–486

    PubMed  CAS  Google Scholar 

  21. Kane PJ, el-Mahdy W, Singh A, Powell MP, Crockard HA (1999) Spinal intradural tumours: Part II. Intramedullary. Br J Neurosurg 13:558–563

    Article  PubMed  CAS  Google Scholar 

  22. Kopelson G, Linggood RM, Kleinman GM, Doucette J, Wang CC (1980) Management of intramedullary spinal cord tumors. Radiology 135:473–479

    PubMed  CAS  Google Scholar 

  23. Kothbauer KF (2007) Neurosurgical management of intramedullary spinal cord tumors in children. Pediatr Neurosurg 43:222–235

    Article  PubMed  Google Scholar 

  24. Kruse CA, Molleston MC, Parks EP, Schiltz PM, Kleinschmidt-DeMasters BK, Hickey WF (1994) A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: a comparison to 9L gliosarcoma. J Neurooncol 22:191–200

    Article  PubMed  CAS  Google Scholar 

  25. Lonjon M, Goh KY, Epstein FJ (1998) Intramedullary spinal cord ependymomas in children: treatment, results and follow-up. Pediatr Neurosurg 29:178–183

    Article  PubMed  CAS  Google Scholar 

  26. Mavinkurve G, Pradilla G, Legnani FG, Tyler BM, Bagley CA, Brem H, Jallo G (2005) A novel intramedullary spinal cord tumor model: functional, radiological, and histopathological characterization. J Neurosurg Spine 3:142–148

    PubMed  Google Scholar 

  27. Medbery CA 3rd, Straus KL, Steinberg SM, Cotelingam JD, Fisher WS (1988) Low-grade astrocytomas: treatment results and prognostic variables. Int J Radiat Oncol Biol Phys 15:837–841

    PubMed  Google Scholar 

  28. Miller DC (2000) Surgical pathology of intramedullary spinal cord neoplasms. J Neurooncol 47:189–194

    Article  PubMed  CAS  Google Scholar 

  29. Parsa AT, Lee J, Parney IF, Weinstein P, McCormick PC, Ames C (2004) Spinal cord and intradural-extraparenchymal spinal tumors: current best care practices and strategies. J Neurooncol 69:291–318

    Article  PubMed  Google Scholar 

  30. Rhines LD, Sampath P, Dolan ME, Tyler BM, Brem H, Weingart J (2000) O6-benzylguanine potentiates the antitumor effect of locally delivered carmustine against an intracranial rat glioma. Cancer Res 60:6307–6310

    PubMed  CAS  Google Scholar 

  31. Salcman M, Botero E, Rao KC, Broadwell RD, Scott E (1984) Intramedullary canine spinal cord tumor model. J Neurosurg 61:761–766

    PubMed  CAS  Google Scholar 

  32. Sandalcioglu IE, Gasser T, Asgari S, Lazorisak A, Engelhorn T, Egelhof T, Stolke D, Wiedemayer H (2005) Functional outcome after surgical treatment of intramedullary spinal cord tumors: experience with 78 patients. Spinal Cord 43:34–41

    Article  PubMed  CAS  Google Scholar 

  33. Sandler HM, Papadopoulos SM, Thornton AF Jr., Ross DA (1992) Spinal cord astrocytomas: results of therapy. Neurosurgery 30:490–493

    Article  PubMed  CAS  Google Scholar 

  34. Stein BM, McCormick PC (1992) Intramedullary neoplasms and vascular malformations. Clin Neurosurg 39:361–387

    PubMed  CAS  Google Scholar 

  35. Steinbok P, Cochrane DD, Poskitt K (1992) Intramedullary spinal cord tumors in children. Neurosurg Clin N Am 3:931–945

    PubMed  CAS  Google Scholar 

  36. Traul DE, Shaffrey ME, Schiff D (2007) Part I: spinal-cord neoplasms-intradural neoplasms. Lancet Oncol 8:35–45

    Article  PubMed  Google Scholar 

  37. Whitaker SJ, Bessell EM, Ashley SE, Bloom HJ, Bell BA, Brada M (1991) Postoperative radiotherapy in the management of spinal cord ependymoma. J Neurosurg 74:720–728

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurological Surgery, Johns Hopkins University, 600 Wolfe Street, Baltimore, MD, 21287, USA

    William A. Pennant, Daniel M. Sciubba, Joseph C. Noggle, Betty M. Tyler, Rafael J. Tamargo & George I. Jallo

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  1. William A. Pennant
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  2. Daniel M. Sciubba
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  3. Joseph C. Noggle
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  4. Betty M. Tyler
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  6. George I. Jallo
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Correspondence to Daniel M. Sciubba.

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Pennant, W.A., Sciubba, D.M., Noggle, J.C. et al. Microsurgical removal of intramedullary spinal cord gliomas in a rat spinal cord decreases onset to paresis, an animal model for intramedullary tumor treatment. Childs Nerv Syst 24, 901–907 (2008). https://doi.org/10.1007/s00381-008-0587-7

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  • DOI: https://doi.org/10.1007/s00381-008-0587-7

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