Carbon-based nanomaterials (CNMs) are being explored for neurological applications. However, systematic in vivo studies investigating the effects of CNM nanocarriers in the brain and how brain cells respond to such nanomaterials are scarce. To address this, functionalised multi-walled carbon nanotubes and graphene oxide (GO) sheets were injected in mice brain and compared with charged liposomes. The induction of acute neuro-inflammatory and neurotoxic effects locally and in brain structures distant from the injection site were assessed up to one week post-administration. While significant neuronal cell loss and sustained microglial cell activation were observed after injection of cationic liposomes, none of the tested CNMs induced either neurodegeneration or microglial activation. Among the candidate nanocarriers tested, GO sheets appeared to elicit the least deleterious neuro-inflammatory profile. At molecular level, GO induced moderate activation of pro-inflammatory markers compared to vehicle control. At histological level, brain response to GO was lower than after vehicle control injection, suggesting some capacity for GO to reduce the impact of stereotactic injection on brain. While these findings are encouraging and valuable in the selection and design of nanomaterial-based brain delivery systems, they warrant further investigations to better understand the mechanisms underlying GO immunomodulatory properties in brain.