Early hippocampal high-amplitude rhythmic spikes predict post-traumatic epilepsy in mice.

Oscillations, a highly conserved brain function across mammalian species, are pivotal in brain physiology and pathology. Traumatic brain injury (TBI) often leads to subacute and chronic brain oscillatory alterations associated with complications like post-traumatic epilepsy (PTE) in patients and animal models. Our recent work longitudinally recorded local field potential from the contralateral hippocampus of 12 strains of recombinant inbred Collaborative Cross (CC) mice alongside classical laboratory inbred C57BL/6J mice after lateral fluid percussion injury. In this study, we profiled the acute (<12 hr post-injury) and subacute (12-48 hr post-injury) hippocampal oscillatory responses to TBI and evaluated their predictive value for PTE. We found dynamic high-amplitude rhythmic spikes with elevated power density and reduced entropy that prevailed during the acute phase in CC031 mice who later developed PTE. This characteristic early brain oscillatory alteration is absent in CC031 sham controls or other CC and reference C57BL/6J strains that did not develop PTE after TBI. Our work provides quantitative measures linking early brain oscillation to PTE at a population level in mice under controlled experimental conditions. These findings will offer insights into circuit mechanisms and potential targets for neuromodulatory intervention.

Genetic diversity drives extreme responses to traumatic brain injury and post-traumatic epilepsy.

Traumatic brain injury (TBI) is a complex and heterogeneous condition that can cause wide-spectral neurological sequelae such as behavioral deficits, sleep abnormalities, and post-traumatic epilepsy (PTE). However, understanding the interaction of TBI phenome is challenging because few animal models can recapitulate the heterogeneity of TBI outcomes. We leveraged the genetically diverse recombinant inbred Collaborative Cross (CC) mice panel and systematically characterized TBI-related outcomes in males from 12 strains of CC and the reference C57BL/6J mice. We identified unprecedented extreme responses in multiple clinically relevant traits across CC strains, including weight change, mortality, locomotor activity, cognition, and sleep. Notably, we identified CC031 mouse strain as the first rodent model of PTE that exhibit frequent and progressive post-traumatic seizures after moderate TBI induced by lateral fluid percussion. Multivariate analysis pinpointed novel biological interactions and three principal components across TBI-related modalities. Estimate of the proportion of TBI phenotypic variability attributable to strain revealed large range of heritability, including >70% heritability of open arm entry time of elevated plus maze. Our work provides novel resources and models that can facilitate genetic mapping and the understanding of the pathobiology of TBI and PTE.

A Good Farewell? Positive Exits from Federal Housing Assistance and Lower Acute Healthcare Utilization.

Little is known regarding the health outcomes of people who exit from housing assistance and if that experience varies by the circumstances under which a person exits. We asked two questions: (1) does the type of exit from housing assistance matter for healthcare utilization? And (2) how does each exit type compare to remaining in housing assistance in terms of healthcare utilization? This retrospective cohort study of 5550 exits between 2012 and 2018 used data from two large, urban public housing authorities in King County, Washington. Exposures were exiting from housing assistance and type of exit (positive, neutral, negative). Outcomes were emergency department visits, hospitalizations, and well-child checks (among those aged < 6) in the year following exit from housing assistance. After adjustment for demographics and baseline healthcare utilization, people with positive exits had 26% (95% confident interval: 6-39%) lower odds of having 1 + ED visits in the year following exit than people with negative exits and 20% (95% CI: 6-31%) lower odds than those who continued receiving housing assistance. Neutral and negative exits did not differ substantially from each other, and both exit types appear to be detrimental to health, with higher levels of ED visits and hospitalizations and lower levels of well-child checks. Why people exit from housing assistance matters. Those with negative exits experience poorer outcomes and efforts should be made to both prevent this kind of exit and mitigate its impact.