Fentanyl Induces Cerebellar Internal Granular Cell Layer Apoptosis in Healthy Newborn Pigs

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• Fentanyl, an opioid, is commonly used for neonatal analgesia and sedation.
• The cerebellum is crucial for motor, cognitive, and behavioral development and is vulnerable to injury.
• Cerebellar cortex plays a vital role in coordination and is susceptible to impaired growth.

Purpose of the Study:

• To investigate the apoptotic effects of continuous intravenous fentanyl infusion on the cerebellum in newborn pigs.

Main Methods:

• Thirteen healthy newborn pigs (<12 hours old) were randomized into two groups: 24-hour intravenous fentanyl infusion (NTFe, n=6) or normothermic controls (NTCTR, n=7).
• Cerebellar sections were morphologically assessed using hematoxylin-eosin staining.
• Apoptosis was quantified by immunostaining for Cleaved caspase-3 and TUNEL in the internal granular cell layer.

Main Results:

• Fentanyl infusion significantly increased the number of cells with apoptotic morphology in the internal granular cell layer.
• Quantification revealed a significant increase in caspase-3-positive (NTFe: 8 vs. NTCTR: 1) and TUNEL-positive cells (NTFe: 6 vs. NTCTR: 1) in the fentanyl group.
• No significant difference in Purkinje cell numbers or physiological parameters was observed between groups.

Conclusions:

• Continuous 24-hour intravenous fentanyl infusion demonstrably increases apoptosis in the cerebellar internal granular cell layer of newborn pigs.
• These findings suggest potential risks of fentanyl exposure to neonatal cerebellar development.