Background

Despite significant scientific advances in chemotherapy (when applicable), radiotherapy, and surgery, malignant tumors of the central nervous system continue to be associated with poor prognosis. In Belgium, the 5-year survival rate among adults remains as low as 22% [1,2]. New emerging treatments are increasingly offering targeted therapies. These therapies aim to modify the tumor microenvironment where the tumor settles and derives essential resources by altering the availability of oxygen and nutrients. More precise targeting of the tumor not only enhances therapeutic efficacy but also reduces off-target toxicity, which often significantly impacts patient quality of life.

The existence of preclinical models designed to evaluate the efficacy of these new therapies is a key element in providing therapeutic opportunities to patients through clinical trials. The implantation of an intracerebral cannula is the method of choice for repeated treatment at the level of the brain, and more specifically within the tumor [3]. Securing the cannula to the brain is a critical step for both the experimental approach and considerations in animal welfare. In this context, various fixation techniques are available, including the use of anchoring screws inserted into the top of the skull (calvaria) and secured with dental cement to anchor the base of the cannula. However, the use of screws is more suitable for rats, where the calvaria is sufficiently thick. In mice, the calvaria is thinner and less calcified, making screw insertion more difficult as there is a risk of damaging the integrity of the skull or the underlying brain tissue [4,5].

The choice of cement is therefore a critical factor in cannula implantation in mice, as the cement alone is responsible for securing the cannula in place. Typically, two types of dental cement are used: zinc polycarboxylate and methyl methacrylate (commonly referred to as pink cement). Zinc polycarboxylate is frequently associated with surgical complications, including skin necrosis, cannula detachment, and infection. Pink cement, although less reactive locally, contains a volatile hydrocarbon that can irritate the respiratory tract.

The use of dental cements that require reconstitution prior to application is relatively constraining as it involves multiple reagents, time-sensitive preparation, and prolonged drying times or UV-induced polymerization [5]. For ethical considerations, animal welfare, and efficient recovery, it is essential to select preparation methods that are as brief as possible to limit the duration of anesthesia. Finally, the polymerization of some cements can generate an exothermic reaction, releasing heat that may reach high temperatures. This thermal effect can lead to burns resulting in necrosis and gliosis (the proliferation of glial cells constituting the supporting tissue of the central nervous system), which remains a significant concern [4].

The protocol presented here describes a method for implanting an intracerebral cannula in mice. This device enables the direct infusion of therapeutic agents directly into the brain, or specifically into the site of a brain tumor that was previously initiated in the animal.