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Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study
U W Thomale1, B Tyler, V M Renard
1Selbständiger Arbeitsbereich Pädiatrische Neurochirurgie, Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Augustenburgr Platz 1, 13353, Berlin, Germany. uthomale@charite.de
Summary
Local chemotherapy delivery to the brainstem using convection-enhanced delivery (CED) is feasible in rats with multiple cannulas. However, carboplatin caused neurological deficits, highlighting the need for less toxic drugs in brainstem CED.
Area of Science:
- Neurosurgery
- Oncology
- Pharmacology
Background:
- Brainstem gliomas are challenging to treat due to the critical location and limited therapeutic options.
- Convection-enhanced delivery (CED) offers a potential route for localized chemotherapy in the brainstem.
- Technical feasibility of multi-cannula CED in the brainstem requires investigation.
Purpose of the Study:
- To assess the feasibility of multiple cannula placements in the rat brainstem for convection-enhanced delivery (CED).
- To evaluate drug distribution and local tissue effects of carboplatin delivered via CED in the brainstem.
- To determine the safety and neurological impact of multi-cannula CED in a rat model.
Main Methods:
- 38 male Fisher rats underwent stereotactic placement of one to three cannulas in the brainstem.
- Carboplatin or vehicle was delivered over 7 days using Alzet pumps at a rate of 1 microl/h.
- Neurological function, drug distribution (platinum concentration), and histological changes were assessed.
Main Results:
- Multi-cannula placement in the rat brainstem was technically feasible.
- Carboplatin delivery resulted in persistent neurological deficits, unlike vehicle delivery.
- Drug distribution was more homogeneous with three cannulas compared to one or two.
- Histological examination revealed localized edema at cannula insertion sites.
Conclusions:
- Unilateral placement of up to three cannulas in the rat brainstem for local drug delivery is feasible.
- The observed neurological deficits with carboplatin underscore the necessity of using low-toxicity agents for CED in the brainstem.
