Arboviruses are viruses transmitted through the bite of blood-feeding arthropods, such as mosquitoes, ticks, sandflies, and midges [1]. Deforestation — and consequent climate changes — and increased international mobility have contributed to arboviruses spreading from endemic to nonendemic areas 2, 3, 4. Several arboviruses have been shown to efficiently adapt to new environments, vectors, and hosts, being the agents of recurrent outbreaks and epidemics around the world, which pose these viruses as relevant global health threats [5]. In line with this notion, in 2022, the World Health Organization launched a Global Arbovirus Initiative, which includes a prevention and preparation plan for arboviral pandemics as one of its pillars [6]. Arbovirus infections in humans result in symptoms ranging from mild to life-threatening, and the most common clinical features include fever, headache, muscle or joint pain, and skin rash.

Aside from common symptoms, involvement of the central nervous system (CNS) is reported in severe arboviral diseases [7]. Most of the neuroinvasive arboviruses belong to the order Bunyavirales or families Flaviviridae and Togaviridae [8]. Neurotropic arboviruses can reach the CNS by mechanisms, such as transcytosis across the blood–brain barrier, trojan horse via infected leukocytes, paracellular entry, or axonal transport 9, 10. The neurological outcomes range from acute — in clinical syndromes such as encephalitis and meningitis — to chronic, which may include cognitive impairment and other neural sequelae [7]. Despite their neurovirulence, the mechanisms by which these viruses lead to neural dysfunction and pathology are poorly understood. Beyond CNS biopsy and autopsy findings, the lack of widespread models to study the virus–host interaction in the human CNS poses a significant challenge to the advance of our knowledge on these mechanisms. Here, we review recent advances in the field of neurotropic arboviruses, focusing on findings obtained using ex vivo human brain tissue as the experimental model.