Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study.
OBJECTIVE
Technical aspects of local chemotherapy in inoperable brainstem gliomas by convection-enhanced delivery (CED) are still under experimental considerations. In this study, we characterize the feasibility of multiple cannula placements in the rat brainstem.


METHODS
In 38 male Fisher rats, up to three guided screws were positioned in burr holes paramedian at 2.5 mm anterior and posterior to as well as at the lambdoid suture. Using Alzettrade mark pumps (1 microl/h flow rate over 7 days) either vehicle (5% dextrose) or 0.1 mg carboplatin was delivered via one, two, or three cannulas, respectively. During cannula insertion, electrocardiogram and respiratory rate was monitored. All rats were subsequently evaluated neurologically for 8 days. For drug distribution in coronal sections, the brain tissue concentration of platinum was measured. HE staining was used to evaluate the local site of drug delivery. Heart and respiratory rate remained within normal range during surgical procedure. Neurological scoring showed only mild neurological impairment in the groups receiving two or three cannulas, which resolved after vehicle delivery. However, after carboplatin delivery, this deficit remained unchanged. Drug distribution was more homogeneous in the three cannula group. Histological slices visualized edematous changes at the sight of cannula placement.


CONCLUSIONS
The unilateral application of up to three cannulas in the brainstem of rats for local drug delivery studies is feasible. The remaining neurological deficit in carboplatin-treated animals underlines the need of low toxicity drugs for CED in the brainstem.
Thomale
U W
UW
Selbständiger Arbeitsbereich Pädiatrische Neurochirurgie, Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Augustenburgr Platz 1, 13353, Berlin, Germany. uthomale@charite.de
Tyler
B
B
Renard
V M
VM
Dorfman
B
B
Guarnieri
M
M
Haberl
H E
HE
Jallo
G I
GI
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001933:Brain Stem / Q000000981:diagnostic imaging* / Q000293:injuries; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002404:Catheterization / Q000009:adverse effects / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004562:Electrocardiography / Q000379:methods; D005240:Feasibility Studies; D008297:Male; D008845:Microinjections; D009460:Neurologic Examination / Q000379:methods / Q000706:statistics & numerical data; D011859:Radiography; D051381:Rats; D011916:Rats, Inbred F344; D013238:Stereotaxic Techniques / Q000295:instrumentation
D000970:Antineoplastic Agents; D016190:Carboplatin