A novel brainstem tumor model: guide screw technology with functional, radiological, and histopathological characterization.
OBJECTIVE
Survival rates for high-grade brainstem tumors are approximately 10% and optimal therapy has yet to be determined. Development of a satisfactory brainstem 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 brainstem tumor model in rats.


METHODS
Thirty female Fischer 344 rats were randomized (10 animals/group) to receive an injection of either 3 ml of 9L gliosarcoma cells (100,000 cells), 3 ml of F98 glioma cells (100,000 cells), or 3 ml of medium (Dulbecco modified Eagle medium) into the pontine tegmentum of the brainstem. Using a cannulated guide screw system implanted in the skull of the animal, rats in each group were injected at coordinates 1.4 mm to the right of the sagittal and 1 mm anterior to the lambdoid sutures, at a depth of 7 mm from the dura mater. The angle of the syringe during injection was anteflexed 5 degrees from the vertical. Postoperatively, the rats were evaluated for neurological deficits by using an automated rotarod test. High-resolution [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) fused with computerized tomography (CT) scans were acquired pre- and postoperatively through the onset of hemiparesis and correlated accordingly. Kaplan-Meier curves were generated for survival and disease progression, and brains were processed postmortem for histopathological investigation. The 9L and F98 tumor cells grew in 95% of the animals in which they were injected and resulted in a statistically significant mean onset of hemiparesis of 16.5 6 0.56 days (p = 0.001, log-rank test), compared with animals in the control group, which had no neurological deficits by Day 45. The FDG-PET studies coregistered with CT scans demonstrated space-occupying brainstem lesions, and this finding was confirmed by histological studies. Animals in the control group showed no functional, radiological, or pathological signs of tumor.


CONCLUSIONS
Progression to hemiparesis was consistent in all tumor-injected animals, with predictable onset of symptoms occurring approximately 17 days postsurgery. The histopathological and radiological characteristics of the 9L and F98 brainstem tumors were comparable to those of aggressive primary human brainstem tumors. Establishment of this animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of these lesions.
Lee
James
J
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jallo
George I
GI
Guarnieri
Michael
M
Carson
Benjamin S
BS
Penno
Margret B
MB
D000818:Animals; D001863:Bone Screws; D020295:Brain Stem Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D018316:Gliosarcoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D009368:Neoplasm Transplantation; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D014057:Tomography, X-Ray Computed / Q000379:methods
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18