ArticleThe Journal of clinical investigation2020
Preventing neuronal edema increases network excitability after traumatic brain injury.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting the KCNC3-Dependent Anterior Insular-Lateral Orbitofrontal Cortex Glutamatergic Circuit Attenuates Post-Traumatic Anxiety.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP4 modulates ZBP1 ubiquitination to regulate microglial PANoptosis and functional outcomes following traumatic brain injury.Cell death and differentiation · 2026Article
- Engineering NO delivery system renormalizes the excitability of inhibitory interneurons after spinal cord injuryBioactive materials · 2025Article
- Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.Experimental physiology · 2025Article
- Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.bioRxiv : the preprint server for biology · 2024Article
- The SWELL1 Channel Promotes Ischemic Brain Damage by Mediating Neuronal Swelling and Glutamate Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Spreading Depolarization Induces a Transient Potentiation of Excitatory Synaptic Transmission.Neuroscience · 2024Article
- Deferoxamine Induces Autophagy Following Traumatic Brain Injury via TREM2 on Microglia.Molecular neurobiology · 2024Article
- Spreading Depolarizations Contribute to the Acute Behavior Deficits Associated With a Mild Traumatic Brain Injury in Mice.Journal of neurotrauma · 2024Article
- Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.Frontiers in molecular neuroscience · 2024Article
- Bumetanide Attenuates Cognitive Deficits and Brain Damage in Rats Subjected to Hypoxia-Ischemia at Two Time Points of the Early Postnatal Period.Neurotoxicity research · 2023Article
- Dexamethasone-Enhanced Continuous Online Microdialysis for Neuromonitoring of OACS chemical neuroscience · 2023Article
- Silencing KCC2 in mouse dorsal hippocampus compromises spatial and contextual memory.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- AQP4 Aggravates Cognitive Impairment in Sepsis-Associated Encephalopathy through Inhibiting NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Role of NKCC1 and KCC2 during hypoxia-induced neuronal swelling in the neonatal neocortex.Neurobiology of disease · 2023Article
- Evaluation of bumetanide as a potential therapeutic agent for Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Co-administration of Nanowired Oxiracetam and Neprilysin with Monoclonal Antibodies to Amyloid Beta Peptide and p-Tau Thwarted Exacerbation of Brain Pathology in Concussive Head Injury at Hot Environment.Advances in neurobiology · 2023Review
- Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis.The Journal of clinical investigation · 2022Article
- Integrated Proteome and Phosphoproteome Analyses Reveal Early- and Late-Stage Protein Networks of Traumatic Brain Injury.Journal of molecular neuroscience : MN · 2022Article
- Neuronal Swelling: A Non-osmotic Consequence of Spreading Depolarization.Neurocritical care · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Edema is an important target for clinical intervention after traumatic brain injury (TBI). We used in vivo cellular resolution imaging and electrophysiological recording to examine the ionic mechanisms underlying neuronal edema and their effects on neuronal and network excitability after controlled cortical impact (CCI) in mice. Unexpectedly, we found that neuronal edema 48 hours after CCI was associated with reduced cellular and network excitability, concurrent with an increase in the expression ratio of the cation-chloride cotransporters (CCCs) NKCC1 and KCC2. Treatment with the CCC blocker bumetanide prevented neuronal swelling via a reversal in the NKCC1/KCC2 expression ratio, identifying altered chloride flux as the mechanism of neuronal edema. Importantly, bumetanide treatment was associated with increased neuronal and network excitability after injury, including increased susceptibility to spreading depolarizations (SDs) and seizures, known agents of clinical worsening after TBI. Treatment with mannitol, a first-line edema treatment in clinical practice, was also associated with increased susceptibility to SDs and seizures after CCI, showing that neuronal volume reduction, regardless of mechanism, was associated with an excitability increase. Finally, we observed an increase in excitability when neuronal edema normalized by 1 week after CCI. We conclude that neuronal swelling may exert protective effects against damaging excitability in the aftermath of TBI and that treatment of edema has the potential to reverse these effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.