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Basic Science and Pathogenesis.

Hailong Song1, Yue Qiu1, Jean-Pierre Dolle1

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Summary
This summary is machine-generated.

Female swine show greater axonal damage after traumatic brain injury (TBI), linked to a higher proportion of small-caliber axons. This sex difference in TBI pathology may influence Alzheimer's disease development.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Traumatic Brain Injury Research

Background:

  • Human females exhibit increased risk and poorer outcomes following traumatic brain injury (TBI).
  • Axonal damage is a critical pathological feature of TBI, yet sex-specific mechanisms remain poorly understood.
  • TBI is a risk factor for Alzheimer's disease (AD), with sex differences observed in AD development.

Purpose of the Study:

  • To investigate sex differences in axonal pathology following TBI.
  • To explore the relationship between axon size and TBI-induced axonal damage.
  • To examine sex differences in the accumulation of amyloid precursor protein (APP) and amyloid-beta (Aβ) in damaged axons post-TBI.

Main Methods:

  • Utilized a swine model of TBI to mimic human head rotational acceleration.
  • Employed immunohistochemical staining to assess APP accumulation and Nav1.6 sodium channel loss.
  • Conducted transmission electron microscopy to evaluate axonal diameter and caliber differences pre- and post-TBI between sexes.

Main Results:

  • Female swine exhibited significantly more APP- and Aβ-laden swollen axons in white matter 24 hours post-TBI.
  • Females showed greater loss of Nav1.6 sodium channels compared to males.
  • Axon degeneration was associated with smaller axon caliber, and females possessed a higher percentage of small-caliber axons, resulting in more extensive injury.

Conclusions:

  • Sex differences in acute axonal pathology following TBI are evident and related to variations in axon diameter.
  • These findings suggest that damaged axons in TBI contribute to APP/Aβ accumulation, potentially linking TBI to AD pathogenesis and its sex disparities.