Journal article
Trauma in Neonatal Acute Brain Slices Alters Calcium and Network Dynamics and Causes Calpain-Mediated Cell Death
eNeuro, Vol.11(7), 0007242024
07/01/2024
DOI: 10.1523/ENEURO.0007-24.2024
PMCID: PMC11232372
PMID: 38886064
Abstract
Preparing acute brain slices produces trauma that mimics severe penetrating brain injury. In neonatal acute brain slices, the spatiotemporal characteristics of trauma-induced calcium dynamics in neurons and its effect on network activity are relatively unknown. Using multiphoton laser scanning microscopy of the somatosensory neocortex in acute neonatal mouse brain slices (propidium iodide or PI) to determine the relationship between cytotoxic Ca2+ loaded neurons (GCaMP-filled) and cell viability at different depths and incubation times. PI+ cells and GCaMPfilled neurons were abundant at the surface of the slices, with an exponential decrease with depth. Regions with high PI+ cells correlated with elevated neuronal and neuropil Ca2+. The number of PI+ cells and GCaMP-filled neurons increased with prolonged incubation. GCaMP-filled neurons did not participate in stimulus-evoked or seizure-evoked network activity. Significantly, the superficial tissue, with a higher degree of trauma-induced injury, showed attenuated seizure-related neuronal Ca2+ responses. Calpain inhibition prevented the increase in PI+ cells and GCaMP-filled neurons in the deep tissue and during prolonged incubation times. Isoform-specific pharmacological inhibition implicated calpain-2 as a significant contributor to trauma-induced injury in acute slices. Our results show a calpain-mediated spatiotemporal relationship between cell death and aberrant neuronal Ca2+ load in acute neonatal brain slices. Also, we demonstrate that neurons in acute brain slices exhibit altered physiology depending on the degree of trauma-induced injury. Blocking calpains may be a therapeutic option to prevent acute neuronal death during traumatic brain injury in the young brain.
Details
- Title: Subtitle
- Trauma in Neonatal Acute Brain Slices Alters Calcium and Network Dynamics and Causes Calpain-Mediated Cell Death
- Creators
- Pratyush Suryavanshi - University of IowaSamuel Baule - University of IowaJoseph Glykys - University of Iowa
- Resource Type
- Journal article
- Publication Details
- eNeuro, Vol.11(7), 0007242024
- DOI
- 10.1523/ENEURO.0007-24.2024
- PMID
- 38886064
- PMCID
- PMC11232372
- NLM abbreviation
- eNeuro
- eISSN
- 2373-2822
- Publisher
- Soc Neuroscience
- Number of pages
- 17
- Grant note
- Iowa Neuroscience Institute University of Iowa, Iowa City, Iowa R01NS115800 / National Institutes of Health/National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) P50 HD103556 / University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center 1066027 / American Epilepsy Society
- Language
- English
- Date published
- 07/01/2024
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984742655902771
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