Prominent astrocytic GLAST pathology occurs in newborn human and piglet hypoxic–ischemic encephalopathy: modeling relationships among laminar neuropathology, seizures, and therapeutic hypothermia
Experimental modeling reveals glutamate transporter abnormalities link seizures and hypoxia–ischemia.
Key Points
This research aims to investigate the role of astrocytic GLAST abnormalities in seizures after neonatal hypoxic-ischemic encephalopathy and the impact of therapeutic hypothermia.
Compared human neonatal HIE and piglet models of hypoxia-ischemia.
Localized GLAST and GFAP using immunoreactivity in brain sections.
Assessed piglet survival and EEG metrics under normothermia and mild hypothermia.
Classified seizure metrics using a custom seizure classification pipeline.
GLAST localization was significantly abnormal in human HIE cortex compared to controls.
Similar GLAST abnormalities were reproduced in HI piglet models.
Therapeutic hypothermia reduced GLAST pathology and delayed seizure onset by ~24 hours.
HT significantly lowered seizure frequency and duration in piglets.