Neuroinflammation is associated with many medical conditions that exhibit both CNS and behavioural changes. Understanding the biological mechanisms underpinning these inflammation-triggered changes may aid therapeutic discovery and further pathophysiological involvement in several neuropsychiatric conditions (e.g. depression and anxiety). Upon activation, toll-like receptor 7 (TLR7) triggers an interferon-mediated inflammatory response. In this study, we utilise the non-invasive, TLR7-activated Aldara Imiquimod mouse model to investigate the transcriptomic changes within the pro-inflammatory neural environment. Imiquimod cream (62.5mg/dose) was applied topically on the mouse shaved back for three consecutive days. Bulk RNA sequencing was performed on whole brain hemisphere homogenate. Over Representation Analysis (ORA) compared our dataset to publicly available databases of biological pathways (e.g. GO terms and KEGG). Spatial transcriptomic analysis of paraffin-embedded coronal mouse brain slices was performed using the Nanostring CosMx platform. Imiquimod topical application induces both a peripheral psoriasis-like dermal response and subsequent neuroinflammation. PCA analysis found distinct groupings of control and treatment groups. Significant gene analysis found 2198 upregulated and 585 downregulated genes following treatment. The most enriched upregulated biological pathways included interferon-related anti-viral responses, T-cell activation, and macrophages. Enriched downregulated pathways included neurexins and neuroligins, glutamate-gated calcium channels and olfactory epithelium. CosMx highlighted interactions between infiltrating peripheral immune populations and brain-resident cells. The Aldara Imiquimod model presents a mild, non-invasive neuroinflammatory model demonstrated by gross transcriptomic changes. Bulk RNA sequencing and CosMx has shown transcriptomic differences between control and treatment groups. Future work hopes to detail common neuroinflammation model characteristics including BBB changes, synaptic proteins and behavioural output.