Environmental enrichment-induced cognitive recovery after a moderate pediatric traumatic brain injury is associated with the gut microbiota and neuroinflammation
Por:
Zamudio-Flores J., Cerqueda D., Phillips-Farfán B., Guerrero-Flores S., Salinas-García A.F., Meléndez-Herrera E., Sélem-Mojica N., Kline A.E., Lajud N.
Publicada:
1 ene 2025
Ahead of Print:
1 dic 2024
Resumen:
Pediatric traumatic brain injury (TBI) is a significant health concern, yet access to rehabilitation therapies for children remains limited. Environmental enrichment (EE) is a preclinical model of neurorehabilitation that promotes behavioral recovery and reduces neuroinflammation after TBI. While the gut microbiota has recently emerged as a potential therapeutic target for treating TBI sequelae in adults, its role in recovery after pediatric TBI remains unclear. Therefore, our aim was to assess the effect of EE on gut microbiota and its correlation with cognition as well as microglial morphology in a preclinical model of pediatric TBI. Male rats underwent a controlled cortical impact of moderate severity or sham injury at postnatal day 21 and were then randomly assigned to either EE or standard (STD) housing. Cognition was evaluated using the Morris water maze (MWM) on post-injury days 14–19. Microglial morphology and caecum microbiota was characterized on post-injury day 21. Cognitive deficits and increased microglial activation in the ipsilateral cortex were observed in the STD-housed TBI rats but not those in EE. TBI decreased microbiota a-diversity, while PERMANOVA analysis showed that both TBI and EE modified microbiota ß-diversity. Furthermore, regression models indicated that microglial morphology in the ipsilateral cortex and Lactobacillus reuteri predicted behavioral outcomes, while Prevotellaceae NK3B31 was associated with microglial morphology. The data suggest that EE mitigates TBI-induced alterations in gut microbiota and that there is a complex interplay between EE, microbiota and microglial morphology that predicts behavioral recovery in pediatric rats. © 2024
Filiaciones:
Zamudio-Flores J.:
División de Neurociencias, Centro de Investigación Biomédica de Michoacán – Instituto Mexicano del Seguro Social, Michoacán, Morelia, Mexico
Instituto de Investigaciones sobre los Recursos Naturales – Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, Morelia, Mexico
Cerqueda D.:
Red de Manejo Biorracional de Plagas y Vectores, Instituto de Ecología, A. C, Xalapa, Mexico
Phillips-Farfán B.:
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría
Guerrero-Flores S.:
Centro de Ciencias Matemáticas, Universidad Nacional Autónoma de, Mexico
Salinas-García A.F.:
División de Neurociencias, Centro de Investigación Biomédica de Michoacán – Instituto Mexicano del Seguro Social, Michoacán, Morelia, Mexico
Instituto de Investigaciones sobre los Recursos Naturales – Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, Morelia, Mexico
Meléndez-Herrera E.:
Instituto de Investigaciones sobre los Recursos Naturales – Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, Morelia, Mexico
Sélem-Mojica N.:
Centro de Ciencias Matemáticas, Universidad Nacional Autónoma de, Mexico
Kline A.E.:
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, United States
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States
Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United States
Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, United States
Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States
Psychology, University of Pittsburgh, Pittsburgh, PA, United States
Lajud N.:
División de Neurociencias, Centro de Investigación Biomédica de Michoacán – Instituto Mexicano del Seguro Social, Michoacán, Morelia, Mexico
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