Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain

Abstract

Objective: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α₂ adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine.

Methods: Systemic saline, ketamine 20 mg/kg, or dexmedetomidine at 30 or 45 μg/kg were given six times to postnatal day 7 rats (n  =  6/group) every 90 min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry.

Results: Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions.

Conclusions: These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.

• Anesthetic
• apoptosis
• developmental
• dexmedetomidine
• ketamine Neonatal
• neurotoxicity
• pediatric

Declaration of interest

This work was supported in part by the Saltonstall Anesthesia Research Fund and the department of Anesthesiology at Tufts Medical Center. Dr. Marchand received funds in the past from Hospira Inc. to study sedative-induced neurotoxicity. However, Hospira did not fund any data presented in the current study.

The authors have no interests to disclose.