Galantamine ameliorates hyperoxia-induced brain injury in neonatal mice

Nahla Zaghloul, Naomi S. Cohen, Kamesh R. Ayasolla, Hsiu Ling Li, Dalibor Kurepa, Mohamed N. Ahmed

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Prolonged oxygen therapy in preterm infants often leads to cognitive impairment. Hyperoxia leads to excess free radical production with subsequent neuroinflammation, astrogliosis, microgliosis and apoptosis. We hypothesized that Galantamine, an acetyl choline esterase inhibitor and an FDA approved treatment of Alzheimer’s disease, will reduce hyperoxic brain injury in neonatal mice and will improve learning and memory. Methods: Mouse pups at postnatal day 1 (P1) were placed in a hyperoxia chamber (FiO2 95%) for 7 days. Pups were injected IP daily with Galantamine (5 mg/kg/dose) or saline for 7 days. Results: Hyperoxia caused significant neurodegeneration in cholinergic nuclei of the basal forebrain cholinergic system (BFCS), laterodorsal tegmental (LDT) nucleus and nucleus ambiguus (NA). Galantamine ameliorated this neuronal loss. Treated hyperoxic group showed a significant increase of choline acetyl transferase (ChAT) expression and a decrease of acetyl choline esterase activity, thus increasing acetyl choline levels in hyperoxia environment. Hyperoxia increased pro-inflammatory cytokines namely IL -1β, IL-6 and TNF α, HMGB1, NF-κB activation. Galantamine showed its potent anti- inflammatory effect, by blunting cytokines surges among treated group. Treatment with Galantamine increased myelination while reducing apoptosis, microgliosis, astrogliosis and ROS production. Long term neurobehavioral outcomes at P60 showed improved locomotor activity, coordination, learning and memory, along with increased hippocampal volumes on MRI with Galantamine treated versus non treated hyperoxia group. Conclusion: Together our findings suggest a potential therapeutic role for Galantamine in attenuating hyperoxia-induced brain injury.

Original languageEnglish (US)
Article number890015
JournalFrontiers in Neuroscience
Volume17
DOIs
StatePublished - 2023

Keywords

  • acetylcholine esterase inhibitor
  • galantamine
  • hyperoxia induced brain injury
  • neuroinflammation
  • reactive oxygen species

ASJC Scopus subject areas

  • General Neuroscience

Fingerprint

Dive into the research topics of 'Galantamine ameliorates hyperoxia-induced brain injury in neonatal mice'. Together they form a unique fingerprint.

Cite this