OSCR

A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice.

Overview

Authors: Jonathan C Vincent1,2,3, Matthew J Lanning2, Kai Saito3, Cate D Cox2, Leke Bytyqi2, Savannah M Shepard2, Blake K Byer2, Margaret R Hawkins2, Teresa Macheda2, Kelly N Roberts2, Heather M Hash2, Kristen A McLaurin4, Josh M Morganti1,2,3, Christopher M Norris1,3,5, Adam D Bachstetter1,2,3
ORCID iDs: Josh M Morganti, Adam D Bachstetter
  1. Department of Neuroscience, University of Kentucky, Lexington, KY 40536-0509, USA
  2. Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536-0509, USA
  3. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0509, USA
  4. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0509, USA
  5. Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536-0509, USA
Institutions: University of Kentucky (United States)
Journal: Brain communications, volume 8, issue 4, article fcag268
Dates: received 9 February 2026; accepted 17 June 2026; published online 12 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1093/braincomms/fcag268 · PMID 42488755 · PMCID PMC13390647 · OpenAlex W7168086206
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), histology / microscopy (modality), mouse (organism), traumatic brain injury (population), cellular / molecular (subfield)
Methods: Statistics, Connectivity, fMRI & imaging
Keywords: diffuse brain injury, sex differences, transcriptomics, field potentials, spine morphology
Topic: Traumatic Brain Injury and Neurovascular Disturbances (Neurology, Medicine), according to OpenAlex
Funding: NIGMS NIH HHS (P20 GM148326); NINDS NIH HHS (R01 NS103785, T32 NS077889, R01 NS120882); NIA NIH HHS (T32 AG078110, R01 AG070830)
Citations: not cited yet (Europe PMC); 87 references in the paper
Research resources: RRID:AB_10013382, CD45 RRID:AB_312967, IBA1 RRID:AB_839504

Abstract

Traumatic brain injury can result in persistent cognitive, behavioural, and emotional deficits, with the hippocampus among the most vulnerable circuits after injury. However, how diffuse injury differentially alters hippocampal subregions across time remains incompletely defined. Here, we used a mouse closed-head injury model to characterize early transcriptomics, subacute-to-chronic electrophysiology, dendritic spine morphology, and delayed immunoreactivity for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (IBA1), and the pan-leukocyte marker CD45. Bulk RNA sequencing at 9, 24, and 72 h post-injury revealed induction of immediate early genes and neuronal excitability transcripts at 9 h alongside inflammatory pathways. These neuronal signatures diminished by 24–72 h while immune-associated programs persisted. Ex vivo field recordings in CA1 and dentate gyrus at 1, 3, and 6 weeks post-injury revealed reductions in synaptic strength in both regions at 1 week. Dentate gyrus deficits persisted at 3 weeks but recovered by 6 weeks, whereas CA1 showed depression at 1 and 6 weeks with relative sparing at 3 weeks. Fibre volley recruitment was preserved across regions and timepoints, arguing against gross presynaptic loss. Population spike thresholds were reduced in both regions, indicating increased neuronal excitability that persisted in CA1 but partially recovered in dentate gyrus. DiOlistic labelling and spine reconstruction revealed stable total spine density, but spine class composition showed sex-dependent injury effects in CA1 with altered mushroom and stubby proportions in males. Immunohistochemistry across 1–8 weeks post-injury revealed cortical gliosis but no injury-related changes in hippocampal GFAP or IBA1, while CD45 immunoreactivity increased in a delayed, sex-dependent manner within hippocampus. Together, these findings show that a single closed-head injury produces sustained hippocampal circuit dysfunction characterized by reduced synaptic strength and increased neuronal excitability, with region-dependent recovery dynamics, preserved presynaptic recruitment, and delayed hippocampal CD45 increases that do not parallel local glial activation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data availability

Bulk RNA-sequencing raw and processed data have been deposited at the Gene Expression Omnibus (GEO) under accession GSE326452 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326452). Electrophysiology, dendritic spine morphology, and immunohistochemistry datasets are publicly available at the Open Data Commons for Traumatic Brain Injury: electrophysiology (ODC-TBI:1593, https://doi.org/10.34945/F5R886), dendritic spine morphology (ODC-TBI:1594, https://doi.org/10.34945/F5MK69), and immunohistochemistry (ODC-TBI:1595, https://doi.org/10.34945/F5GS30). RNA-sequencing analysis used the nf-core/rnaseq pipeline (v3.21.0), DESeq2 (v1.46.0), clusterProfiler (v4.14.6), and ReactomePA (v1.50.0) with parameters reported in Methods. Figure visualizations were generated using standard plotting functions from these packages and ggplot2 with parameters reported in Methods. Additional analytical details are available from the corresponding author upon reasonable request. Tissue samples are not available for future use.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 5 keywords, 3 funders, 87 references, 3 RRIDs.

Cite

This paper

Vincent, J. C., Lanning, M. J., Saito, K., Cox, C. D., Bytyqi, L., Shepard, S. M., Byer, B. K., Hawkins, M. R., Macheda, T., Roberts, K. N., Hash, H. M., McLaurin, K. A., Morganti, J. M., Norris, C. M., & Bachstetter, A. D. (2026). A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice. Brain communications, 8(4), fcag268. https://doi.org/10.1093/braincomms/fcag268

BibTeX

@article{vincent2026single,
author = {Vincent, Jonathan C and Lanning, Matthew J and Saito, Kai and Cox, Cate D and Bytyqi, Leke and Shepard, Savannah M and Byer, Blake K and Hawkins, Margaret R and Macheda, Teresa and Roberts, Kelly N and Hash, Heather M and McLaurin, Kristen A and Morganti, Josh M and Norris, Christopher M and Bachstetter, Adam D},
title = {{A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice}},
journal = {Brain communications},
year = {2026},
month = jul,
volume = {8},
number = {4},
pages = {fcag268},
publisher = {Oxford University Press},
issn = {2632-1297},
doi = {10.1093/braincomms/fcag268},
url = {https://doi.org/10.1093/braincomms/fcag268},
pmid = {42488755},
pmcid = {PMC13390647}
}

RIS

TY - JOUR
AU - Vincent, Jonathan C
AU - Lanning, Matthew J
AU - Saito, Kai
AU - Cox, Cate D
AU - Bytyqi, Leke
AU - Shepard, Savannah M
AU - Byer, Blake K
AU - Hawkins, Margaret R
AU - Macheda, Teresa
AU - Roberts, Kelly N
AU - Hash, Heather M
AU - McLaurin, Kristen A
AU - Morganti, Josh M
AU - Norris, Christopher M
AU - Bachstetter, Adam D
TI - A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice
T2 - Brain communications
J2 - Brain Commun
PY - 2026
DA - 2026/07/12
VL - 8
IS - 4
SP - fcag268
SN - 2632-1297
PB - Oxford University Press
DO - 10.1093/braincomms/fcag268
UR - https://doi.org/10.1093/braincomms/fcag268
LA - en
ER -

CSL-JSON

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