Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model.
OBJECTIVE
Convection-enhanced delivery using carboplatin in brainstem glioma models was reported to prolong survival. Functional impairment is of additional importance to evaluate the value of local chemotherapy. We established a neurological scoring system for the rat brainstem glioma model.


METHODS
In 46 male Fisher rats stereotactically 10(5) F-98 cells were implanted at 1.4-mm lateral to midline and at the lambdoid suture using guided screws. Following 4 days local delivery was performed using Alzet pumps (1 microl/h over 7 days) with either vehicle (5% dextrose) or carboplatin via one or two cannulas, respectively. All rats were subsequently tested neurologically using a specified neurological score. In 38 animals survival time was recorded. Representative MR imaging were acquired in eight rats, respectively, at day 12 after implantation. HE staining was used to evaluate tumor extension.


RESULTS
Neurological scoring showed significantly higher impairment in the high dose carboplatin group during the treatment period. Survival was significantly prolonged compared to control animals in the high dose carboplatin-one cannula group as well as in both low dose carboplatin groups (18.6 +/- 3 versus 26.3 +/- 9, 22.8 +/- 2, 23.6 +/- 2 days; p < 0.05). Overall neurological grading correlated with survival time. MR imaging showed a focal contrast enhancing mass in the pontine brainstem, which was less exaggerated after local chemotherapy. Histological slices visualized decreased cellular density in treatment animals versus controls.


CONCLUSIONS
Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival. Our neurological grading enables quantification of drug and tumor-related morbidity as an important factor for functional performance during therapy.
Thomale
U W
UW
Division of Pediatric Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. uthomale@charite.de
Tyler
B
B
Renard
V
V
Dorfman
B
B
Chacko
V P
VP
Carson
B S
BS
Haberl
E J
EJ
Jallo
G I
GI
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001835:Body Weight; D020295:Brain Stem Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D016190:Carboplatin / Q000627:therapeutic use; D002404:Catheterization; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D009367:Neoplasm Staging; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012720:Severity of Illness Index
D000970:Antineoplastic Agents; D016190:Carboplatin