Fentanyl induces cerebellar internal granular cell layer apoptosis in healthy newborn pigs

Hemmen Sabir, John Dingley, Emma Scull-Brown, Ela Chakkarapani, Marianne Thoresen

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
226 Downloads (Pure)


Background: Opioids like fentanyl are regularly used in neonates for analgesia and sedation. So far, they have been reported to be safe and eligible to use. The cerebellum has become a focus of neurodevelopmental research within the last years, as it is known to play an important role in long-lasting motor, cognitive and other behavioral changes. The cerebellar cortex is of major importance in the coordinative role of the cerebellum and highly vulnerable to injury and impaired growth.Objective: This study was performed to evaluate the apoptotic effect of intravenous fentanyl infusion on the cerebellum in healthy newborn pigs. Methods: Thirteen healthy pigs (<median 12 h old) were randomized into: (1) 24 h of intravenous fentanyl at normothermia (NTFe, n=6) or (2) non-ventilated controls at normothermia (NTCTR, n=7). Cerebellar sections were morphologically assessed after staining with Hematoxylin-Eosin. In addition, paired sections were immuno-stained for cell death (cleaved caspase-3 and TUNEL) and positive cells were counted in defined areas of the internal granular cell layer. In total, cells in three cerebellar gyri were counted. Results: We found that there was an increase in cells with apoptotic morphology in the internal granular cell layer in the NTFe group. For quantification, we found a significant increase in cell death in group (1) (median (range) number of caspase-3 positive cells group (1) 8 (1-22) vs. group (2) 1 (1-6) and TUNEL positive cells (1) 6 (1-10) vs. (2) 1 (0-4)). In both groups, there was no difference in the number of Purkinje cells. Both groups had comparable and stable physiological parameters throughout the 24h period.Conclusions: Twenty-four hours of continuous intravenous fentanyl infusion increased apoptosis in the internal granular cell layer in the cerebellum of healthy newborn pigs.
Original languageEnglish
Article number294
JournalFrontiers in Neurology
Issue numberMay
Early online date1 May 2018
Publication statusE-pub ahead of print - 1 May 2018


  • newborn
  • brain
  • neurotoxicity
  • opioids
  • sedation

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