A novel model of intramedullary spinal cord tumors in rats: functional progression and histopathological characterization.
OBJECTIVE
Intramedullary spinal cord tumors are difficult lesions to treat given their recurrence rate and limited treatment options. The absence of an adequate animal model, however, has hindered the development of new treatment paradigms. In this study, we describe the technique for intramedullary injection of two experimental rodent gliomas (9L and F98) and present the methodology for functional and histopathological analysis of tumor progression.


METHODS
F344 rats (n = 24) were randomized into three groups. Group 1 (n = 8) received a 5 microl intramedullary injection of Dulbecco's modified Eagle medium, Group 2 received a 5 microl intramedullary injection of 9L gliosarcoma (100,000) cells, and Group 3 received a 5 microl intramedullary injection of F98 glioma (100,000) cells. The animals were anesthetized, a 2 cm incision was made in the dorsal mid-thoracic region, and the spinous process of the T5 vertebrae was removed to expose the intervertebral space. The ligamentum flavum was removed, and an intramedullary injection was made into the spinal cord. The animals were evaluated daily for signs of paralysis using the Basso, Beattie, and Bresnahan scale and sacrificed after the onset of deficits for histopathological analysis.


RESULTS
Animals injected with 9L-gliosarcoma had a median onset of hind limb paresis at 12 +/- 2.9 days. Animals injected with F98 glioma had a median onset of hind limb paresis at 19 +/- 3 days. Animals injected with Dulbecco's modified Eagle medium did not show neurological deficits. Hematoxylin-eosin cross sections confirmed the presence of intramedullary 9L and F98 tumor invading the spinal cord. Control animals had no significant histopathological findings.


CONCLUSIONS
Animals injected with 9L or F98 consistently developed hind limb paresis in a reliable and reproducible manner. The progression of neurological deficits is similar to that seen in patients with intramedullary spinal cord tumors. These findings suggest that this model mimics the behavior of intramedullary spinal cord tumors in humans and may be used to examine the efficacy of new treatment options for both low- and high-grade intramedullary tumors.
Caplan
Justin
J
Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287, USA.
Pradilla
Gustavo
G
Hdeib
Alia
A
Tyler
Betty M
BM
Legnani
Federico G
FG
Bagley
Carlos A
CA
Brem
Henry
H
Jallo
George
G
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology*; D018316:Gliosarcoma / Q000473:pathology / Q000503:physiopathology; D006614:Hindlimb; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010291:Paresis / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000473:pathology; D013120:Spinal Cord Neoplasms / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*