A rat glioblastoma model with diffuse leptomeningeal gliomatosis induced by intracarotid injection of C6 glioma cells.
OBJECTIVE
A reproducible brain tumor model using experimental animals is required to study biological behavior and develop more potent antineoplastic drugs and effective therapeutic modalities. In this work, we attempted to establish diffuse leptomeningeal gliomatosis in the rat by intracarotid injection of C6 glioma cells.


METHODS
Intracarotid injection of 1 x 10(7) C6 glioma cells in Wistar rats was performed to establish a primary diffuse leptomeningeal gliomatosis model. Ki-67 and matrix metalloproteinases (MMPs) immunohistochemistry staining were used to study the biological behavior of the developed tumor. Methodology, physical findings and histopathological features were also discussed.


RESULTS
Leptomeningeal gliomas grew in all Wistar rats after the administration of 1 x 10(7) C6 glioma cells. Intracranial hypertension, weight loss and cachexia developed, and the median survival time was 18.0 +/- 2.9 days. The glioma mass distributed throughout the ventricles, the leptomeningeal regions in the brain and the brainstem, with typical pathological features of glioblastoma. The immunohistochemistry stainings showed high Ki-67 labeling index (42.1 +/- 10.3%), and concomitant overexpression of MMP-2 and MMP-9 suggested proliferation, invasion and angiogenesis potential.


CONCLUSIONS
The advantage of the intracarotid injection route is the absence of an operative scar in the cranium. This established animal model is a novel model of primary diffuse leptomeningeal gliomatosis. This model probably can be used for pre-clinical testing in the progression of glioblastoma.
Wasita
Brian
B
Department of Neurosurgery, Faculty of Medicine, Tottori University, Yonago,Tottori, Japan.
Kamitani
Hideki
H
Kinoshita
Yusuke
Y
Mamun
Mahabub Hasan
MH
Watanabe
Takashi
T
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002100:Cachexia / Q000503:physiopathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005910:Glioma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007427:Intracranial Pressure; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9