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Probiotics restore GABAergic neurons and attenuate postnatal seizures in periventricular leukomalacia

Jia-Shing Chen1, Ming-Jung Tu2, Yu-Ming Chang3,4

  • 1School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.

Nutritional Neuroscience
|November 11, 2025
PubMed

Insights

Probiotics may prevent epilepsy after periventricular leukomalacia (PVL) brain injury. Supplementation reduced seizures, neuroinflammation, and restored GABAergic neurons by influencing the gut-brain axis.

Area of Science:

  • Neuroscience
  • Microbiology
  • Developmental Biology

Background:

  • Postnatal epilepsy frequently follows periventricular leukomalacia (PVL) in preterm infants, often proving treatment-resistant.
  • The mechanisms underlying PVL-induced epilepsy and effective preventive strategies remain largely unknown.
  • Probiotics, known for modulating gut microbiota and reducing inflammation, present a potential therapeutic avenue.

Purpose of the Study:

  • To investigate the efficacy of probiotic supplementation in preventing or mitigating seizures and associated neuropathology following PVL in a rat model.
  • To explore the impact of probiotics on neuroinflammation, GABAergic neuron integrity, and gut microbiota composition in the context of PVL.

Main Methods:

  • Periventricular leukomalacia (PVL) was induced in rats via hypoxia-ischemia and lipopolysaccharide.
  • Seizure susceptibility, neuroinflammation markers (microgliosis, TNF-α), GABAergic neuron density, and gut microbiota were assessed.
  • Rats received a multi-strain probiotic formulation (Lactobacillus, Bifidobacterium) in prebiotics (GOS, FOS) before and after injury.

Main Results:

  • PVL rats exhibited increased seizure frequency and duration, microgliosis, reduced oligodendrocytes, and decreased myelin.
  • A significant reduction in cortical GABAergic neurons, especially somatostatin-positive interneurons, was noted in PVL rats.
  • Probiotic treatment restored GABAergic neurons, decreased seizure activity, reduced microglial activation, and lowered TNF-α levels.
  • Probiotics modulated gut microbiota composition and increased butyric acid levels in feces and cerebrospinal fluid (CSF).

Conclusions:

  • Probiotic supplementation shows promise in reducing seizure activity post-PVL brain injury.
  • The therapeutic effects appear mediated through the gut-brain axis, involving reduced neuroinflammation and restoration of GABAergic neurons.
  • Probiotics may represent a viable adjuvant therapy for preventing epilepsy in infants with PVL.

Keywords:
GABergic neuronsProbioticsfecal microbiomeneuroinflammationperiventricular leukomalaciapostnatal epilepsypremature brainshoft chain fatty acid

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