A novel intramedullary spinal cord tumor model: functional, radiological, and histopathological characterization.
OBJECTIVE
Survival rates for high-grade intramedullary spinal cord tumors (IMSCTs) are approximately 30%, and optimal therapy has yet to be determined. Development of a satisfactory intramedullary tumor model is necessary for testing new therapeutic paradigms that may prolong survival. The authors report the technique, functional progression, radiological appearance, and histopathological features of a novel intramedullary model in rabbits.


METHODS
Ten New Zealand white rabbits were randomized to receive an intramedullary injection of either 25 microl of VX2 carcinoma cells (500,000 cells; six rabbits) or 25 microl of medium (Dulbecco modified Eagle medium; four rabbits) into the midthoracic spinal cord. Postoperatively the rabbits were evaluated twice daily for neurological deficits. High-resolution magnetic resonance (MR) images were acquired preoperatively and weekly postoperatively until onset of paraparesis, at which point the animals were killed, and the midthoracic spines were processed for histopathological examination. The VX2-carcinoma cells grew in 100% of animals injected and resulted in a statistically significant mean onset of paraparesis of 16.8 +/- 1.7 days (p = 0.0035, log-rank test), compared with animals in the control group in which neurological deficits were absent by Day 45. Contrast-enhanced T1-weighted MR imaging best demonstrated space-occupying intramedullary lesions and histopathological findings confirmed the intramedullary location of the tumor. Animals in the control group exhibited no functional, radiographic, or pathological signs of tumor.


CONCLUSIONS
Progression to paraparesis was consistent in all the VX2-injected animals, with predictable onset of paraparesis occurring approximately 17 days postinjection. Histopathological and radiological characteristics of the VX2 intramedullary tumor are comparable with those of aggressive primary human IMSCTs. Establishment of this novel animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of IMSCTs.
Mavinkurve
Gaurav
G
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Pradilla
Gustavo
G
Legnani
Federico G
FG
Tyler
Betty M
BM
Bagley
Carlos A
CA
Brem
Henry
H
Jallo
George
G
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005242:Fecal Incontinence / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D020335:Paraparesis / Q000209:etiology; D011817:Rabbits; D013120:Spinal Cord Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D014549:Urinary Incontinence / Q000209:etiology