Anesthetic-Induced Neuroapoptosis

Identifying mechanisms of anesthetic toxicity to mitigate risks for newborns

Full Project Name:Anesthetic-Induced Developmental Neuroapoptosis: Is Anesthesia Bad for the Newborn Brain?Principal Investigator:Zeljko Bosnjak, PhD, AnesthesiologyCo-Investigator:Xiaowen Bai, PhD, Cellular Biology; John A. Corbett, PhD, BiochemistryAward Amount:600,000

Award Date

January2012

Project Duration:48 months

Project Description Narrative:

Children exposed to anesthesia in early life have higher incidence of learning disabilities later in life. Epidemiological studies of multiple anesthetic exposures have clearly been shown to be detrimental for cognitive development of children, the mechanisms by which this toxicity occurs remain largely unknown. While research continues, children will still need to undergo surgical and medical procedures for which these drugs are essential to their safety and comfort.

Through this award, investigators aim to identify the mechanisms of anesthetic toxicity in developing human nerve cells in order to assure the future safety of general anesthesia for children by mitigating risks or identifying anesthetics that are not toxic for the newborn brain.

Outcomes & Lessons Learned:

Identified that propofol exposure at higher concentrations than used clinically increased stem cell-derived neuron death, decreased mitochondrial membrane potential, and led to a detrimental increase in mitochondrial fission
Identified propofol-induced cell death at lower doses after multiple exposures
Reported on the role of miR-21 in propofol-induced neurotoxicity, demonstrating for the first time that propofol-induced neurotoxicity occurs through a mitochondrial fission-mediated pathway and miR-21 downregulation
Utilized studies to advance protective approaches for further study in future in vitro cell culture or intact animal models
Disseminated findings through numerous published studies and reviews