Quantitative ultrasound and apoptotic death in the neonatal primate brain

Abstract

Apoptosis is triggered in the developing mammalian brain by sedative, anesthetic or antiepileptic drugs during late gestation and early life. Whether human children are vulnerable to this toxicity mechanism remains unknown, as there are no imaging techniques to capture it. Apoptosis is characterized by distinct structural features, which affect the way damaged tissue scatters ultrasound compared to healthy tissue. We evaluated whether apoptosis, triggered by the anesthetic sevoflurane in the brains of neonatal rhesus macaques, can be detected using quantitative ultrasound (QUS).

Anesthesia and neurotoxicity study design, execution, and reporting in the nonhuman primate: A systematic review

“…Twelve (12/23) studies reported that all animals survived the anesthetic procedure 24,26–29,33,34,37–40,42 . Other 11/23 studies did not address animal survival following exposure 16,22,23,25,30–32,35,36,41,43 .…”

“…Eighty percent (12/15) of mechanically ventilated studies monitored fraction of inspired oxygen 16,23,26–29,33,35,37–40 . Eighty‐seven percent (20/23) of studies monitored blood pressure, 16,23–30,32–41,43 and ninety‐one percent (21/23) of studies monitored temperature 16,23–30,32–43 …”

“…Mean (SD) sample size in neurobehavioral studies was 8 (1) animals per group while mean (SD) sample size in neuroapoptosis studies was 5 (3) animals per group. In 19/23 (83%) studies, 16,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] animals were randomized to study group, 13/23 (57%) studies [26][27][28][29][30]32,33,[38][39][40][41][42] were blinded during the entirety of data collection and 0/23 (0%) studies were blinded during data analysis. In only 2/23 (9%) studies, a priori power calculation was performed to justify sample size.…”

“…Controlled ventilation was employed in 15/23 (65%) of studies, 16,23,[26][27][28][29]31,33,35,[37][38][39][40][41][42] and spontaneous ventilation was employed in 5/23 (22%) of studies. 24,25,30,36,43 Ventilation method was not specified in 3/23 (13%) of studies.…”

“…Twelve (12/23) studies reported that all animals survived the anesthetic procedure. 24,[26][27][28][29]33,34,[37][38][39][40]42 Other 11/23 studies did not address animal survival following exposure. 16,22,23,25,[30][31][32]35,36,41,43 One behavioral study reported death in a treatment subject 4 months after undergoing anesthesia.…”