Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment

Abstract

Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community. The apoptotic degenerative response resulting from neonatal exposure to ASAs has been replicated in many studies in both rodents and non-human primates, suggesting that a similar effect may occur in humans. In both rodents and non-human primates, significantly increased levels of apoptotic degeneration are often associated with functional impairments later in life. However, behavioral deficits following developmental ASA exposure have not been consistently reported even when significantly elevated levels of apoptotic degeneration have been documented in animal models. In the present work, we review this literature and propose a rodent model for assessing potential functional deficits following neonatal ASA exposure with special reference to experimental design and procedural issues. Our intent is to improve test sensitivity and replicability for detecting subtle behavioral effects, and thus enhance the translational significance of ASA models.

Effect of remimazolam tosilate on early cognitive function in elderly patients undergoing upper gastrointestinal endoscopy

“…How these effects of RT relate to the adult human brain is unclear, although it has been hypothesized that the effects of centrally acting GABAA agents are dependent on the cumulative dose of the agent administered and neuronal susceptibility 17 . However, there was no deterioration in long‐delayed memory in patients, which indicated that RT distinctively impaired the acquisition stage rather than the storage and retrieval stages of the memory process.…”

Caffeine reverses the unconsciousness produced by light anesthesia in the continued presence of isoflurane in rats

“…Recent studies in animals and humans suggest that general anesthetics including volatile agents, may be neurotoxic in very young [47][48][49] and very old human and animal populations [50,51]. This anesthetic-induced neurotoxicity effect appears to be dose, frequency and duration-dependent [48,49]. Many critically ill patients do not tolerate high concentrations of volatile agents due to anesthetic's side effects on hemodynamic stability.…”

Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit

“…Concerns for adverse neurologic effects after surgical anesthesia in young children prompted a Safety Communication from the United States Food and Drug Administration in 2016 warning against the prolonged or repeated use of general anesthesia in children under the age of 3 years and pregnant women (United States Food and Drug Administration Safety Communication (FDA), 2019). This warning came after several retrospective studies reported learning disabilities and lower standardized test scores in children who underwent elective surgery as infants or toddlers (DiMaggio et al, 2011(DiMaggio et al, , 2012Flick et al, 2011;Block et al, 2012), and experiments of anesthesia in young animals found increased neuronal death and abnormal synaptic plasticity to explain this cognitive dysfunction (Sanders et al, 2013;Jevtovic-Todorovic, 2018;Maloney et al, 2018). More recently, however, larger prospective studies of isolated anesthesia during infancy have not found a clear effect on cognition, though assessments may be limited by age-appropriate metrics in very young children (Sun et al, 2016;Warner et al, 2018;McCann et al, 2019).…”