Decrease of glial cell-derived neurotrophic factor contributes to anesthesia- and surgery-induced learning and memory...

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Anesthesiology

Background:

• Anesthesia and surgery can negatively impact the developing brain.
• The specific mechanisms and consequences of combined anesthesia-surgery on neonatal brain development are not well understood.

Purpose of the Study:

• To investigate the effects of anesthesia combined with surgery on cognitive function, neuroinflammation, and glial cell-derived neurotrophic factor (GDNF) levels in neonatal rats.
• To elucidate the role of GDNF in anesthesia-surgery-induced cognitive impairment.

Main Methods:

• Neonatal Sprague-Dawley rats were exposed to sevoflurane anesthesia with or without common carotid artery exposure.
• Treatments included pyrrolidine dithiocarbamate (PDTC), anti-GDNF antibody, or GDNF administration.
• Cognitive function was assessed using the Barnes maze and fear conditioning tests.
• Neuroinflammation, GDNF levels, and hippocampal neurogenesis were evaluated.

Main Results:

• Anesthesia-surgery induced significant learning and memory impairments in neonatal rats.
• This impairment was associated with increased neuroinflammation, reduced hippocampal GDNF levels, and decreased neurogenesis.
• PDTC treatment mitigated these effects, while anti-GDNF antibody exacerbated cognitive deficits, and GDNF administration attenuated them.

Conclusions:

• Combined anesthesia-surgery in neonatal rats triggers neuroinflammation, leading to reduced GDNF and hippocampal neurogenesis, ultimately causing cognitive impairment.
• Decreased GDNF levels play a critical role in the cognitive deficits observed after anesthesia-surgery in the developing brain.