A novel ex vivo model for studying SARSCoV2 induced neuroinflammation and microglial spine pruning.

Recent evidence suggests that COVID19 infection targets the CNS causing interleukinsmediated brain inflammation [1], activation of microglia, and neuronal damage, reminiscent of what is observed in human neurodegenerative disorders [2]. Despite the social and clinical Neurocovid burden, the study of pathology on animal models lacks significant preclinical data. In particular, in vitro and/or exvivo Neurocovidlike experimental paradigms allowing pharmacological manipulation and electrophysiological assays would represent a good implementation to preclinical research in the field. Recently, intracerebroventricular injection of the human spike protein was regarded to promote inflammation, microglial TLR4 activation, and memory dysfunction in Swiss mice [3]. Nonetheless, the extensive characterization of the morphofunctional pattern of microglia activation induced by the human Spike in the mouse brain awaits further investigations. In line with this, the main aims of this study are: 1) to set up a novel exvivo Neurocovid model mimicking SARSCoV2driven brain inflammation using mouse brain slices culture, 2) investigate microglial activation/phenotype and neuronal spine clearance by a cuttingedge superresolution imaging technique, Expansion Microscopy (ExM) [45], 3) assess LTP pattern upon Spike incubation in brain slices [6]. In conclusion, a deeper understanding of the role played by microglia in COVID19 neuroinflammation will potentially enable the evaluation of a novel approach to COVID19 therapy, including the use of antispike monoclonal antibodies like Pronectins [7].