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Viral neurotropism is linked to chronic glial-mediated neuroinflammation and increased risk for neurodegenerative disorders including Alzheimer disease and Parkinson disease. We previously showed that sublethal WEEV infection induces nigrostriatal gliosis, neuronal loss, and Parkinsonian-like motor deficits in mice. However, the temporal progression of glial activation and neurodegeneration in brain regions relevant to dementia remains unclear. To address this, we performed a longitudinal assessment of hippocampal pathology following intranasal infection with McMillan WEEV. Brain tissue was collected at 1, 2, and 4\u2009weeks postinfection and analyzed using high-content fluorescence imaging, deep learning-based image analysis, and population-level cellular phenotyping. We observed a marked increase in gliosis peaking at 1-week postinfection, coinciding with fibrotic, immune cell-dense lesions that inversely correlated with eosinophilic neuronal density. Automated skeletonization analysis revealed increased astrocyte reactivity and a predominantly bushy microglial morphology at this time point. Heat map densitometry further demonstrated progressive amyloid-\u03b2 accumulation across all time points. Together, these findings define a dynamic sequence of glial activation, lesion formation, and protein aggregation underlying WEEV-induced hippocampal neurotoxicity.<\/jats:p>","DOI":"10.1093\/jnen\/nlag097","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:45:08Z","timestamp":1786535108000},"source":"Crossref","is-referenced-by-count":0,"title":["Infection with Western equine encephalitis virus causes severe regional glial reactivity and neurodegeneration in the hippocampus with progressive accumulation of amyloid-\u03b2"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4960-6520","authenticated-orcid":false,"given":"Aidan M","family":"Briggs","sequence":"first","affiliation":[{"name":"Department of Neurology, Barrow Neurological Institute , Phoenix, AZ,","place":["United States"]},{"name":"Department of Environmental and Radiological Health Sciences, Colorado State University , Fort Collins, CO,","place":["United 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