The Weight of Multiple Hits: How TBI and Infectious Encephalitis Co-Modulate Adverse Outcomes

Compared to patients with no TBI history, patients with a TBI history at least one month before infectious encephalitis have an increased risk of mortality, epilepsy, and dementia or delirium. Those with a history of TBI have an increased risk of various outcomes, including mortality, epilepsy, and dementia. Bulk RNA sequencing of the hippocampus from mice subjected to CCI injury and VEEV infection demonstrated that key pathways, specifically those involved in granzyme-mediated cell death, were enriched compared to VEEV infection alone. All experimental procedures were performed on male mice aged 8–10 weeks. In brief, mice received a controlled cortical impact 1.5 months before VEEV inoculation and were sacrificed one week later for hippocampal tissue extraction (Figure 5). Mice were split into three groups: mock, VEEV, and TBI/VEEV (n=4/group). All studies complied with the guidelines outlined in the NIH Guide for the Care and Use of Laboratory Animals. Controlled cortical impact. Surgeries were conducted following established procedures [38-42]. Mice were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg), and buprenorphine SR (0.5 mg/kg) was administered subcutaneously before surgery. A Φ = 4 mm craniotomy was made over the right parietal bone (− 2.5 mm A/P and 2.0 mm lateral from bregma). Cortical injury was induced using an electronic controlled cortical impactor (Custom design and fabrication; Φ = 3 mm round tip) at a velocity of 5.0 m/s, depth of 2.0 mm, and 150 ms dwell time. Mice were intranasally infected with 2x107 PFU of VEEV TC-83 (except for uninfected control mice).