Martynyuk Laboratory: Neurosciences in Anesthesiology

Our research

We use animal models to investigate long-term neurobehavioral abnormalities in parents exposed to anesthesia, surgery and/or neurodegenerative diseases and in their unexposed offspring conceived after a parental exposure (an animal model of intergenerational perioperative neurocognitive disorder, or intergenerational PND) [Biology (Basel). 2023; 12: 567]. The lab’s current studies are based on our recent findings that rats exposed to the general anesthetic sevoflurane, either during the early postnatal period or in young adulthood, pass on neurobehavioral abnormalities to their offspring, with male offspring affected more than female offspring (Br J Anaesth. 2018; 121: 406-16; Anesthesiology. 2019; 131:1092-1109). Remarkably, intergenerational outcomes are even more profound when exposures to sevoflurane are combined with surgery and traumatic brain injury (TBI) (Anesthesiology. 2023;138: 388-402; J Neurotrauma. 2024 Jan 27. doi: 10.1089/neu.2023.0364. PMID: 38279844). Considering that many younger individuals, who were exposed to anesthesia, surgery and TBI, become parents later in life, it is scientifically and translationally important to understand the impact of paternal and maternal anesthesia, surgery and TBI on brain development in male and female offspring. The overarching goal of our work is to improve outcomes of parental anesthesia, surgery and TBI by providing critical data needed to establish a mechanistic basis for studies in patient populations.

Our ongoing research projects

1. A study, funded by the National Institutes of Health (NIH), investigates mechanisms, transcriptomic blood-based biomarkers, and potential targets for pharmacological therapies of the heritable effects of general anesthetics administered to young adult rats.
2. A second line of research was inspired by the findings of human studies that children of parents with TBI are more likely to develop psychiatric disorders (Brain Inj. 2018; 32: 933-40). Mechanisms of intergenerational transmission of such neuropsychiatric disorders are not known and are often assumed to result from TBI-induced changes in parental personality or family dynamics – ie., “social” transmission. The most recent findings from the lab suggest that offspring of sires with a history of a moderate TBI that involved surgery under sevoflurane anesthesia, develop neurobehavioral abnormalities (affecting male offspring more  than female) even though direct social interaction between the sire and the offspring does not occur in rats, thus suggesting biological transmission (Anesthesiology. 2023;138: 388-402; J Neurotrauma. 2024 Jan 27. doi: 10.1089/neu.2023.0364. PMID: 38279844).  Depending on whether social, biological or both modes of transmission are involved, different preventive strategies may be needed to improve adverse neurocognitive outcomes in offspring. To lay a foundation for future clinical studies, the lab explores the neurocognitive consequences for offspring of maternal and paternal moderate TBI, the roles of biological vs. social parent-child transmission of neurocognitive effects of parental TBI, how offspring sex affects vulnerability, initiating mechanisms and biomarkers of parental TBI-induced intergenerational abnormalities, and pharmacotherapeutic approaches to minimize them.
3. Another current ongoing rat study in the lab is also driven by the results of human studies that found poorer neurocognitive performance than expected in both twins, even though only one of the twins had early life exposure to general anesthesia (Twin Res Hum Genet. 2009; 12: 246-53). We found that under strictly controlled experimental conditions co-housed neonatally sevoflurane-exposed and unexposed male rat cagemates developed the same deficiencies at the gene expression, neuroendocrine, neuroinflammation and behavioral levels (Anesthesiology. 2023; 138: 658-61), supporting that co-housing of neonatally sevoflurane-exposed and unexposed cagemates is an active ingredient for the development of comparable deficiencies. These findings suggest that in studies of anesthesia-induced neurodevelopmental abnormalities in particular, and neurocognitive development in general, interactions between cohabitants should be considered as a factor that may influence outcomes.
4. Finally, the lab is working to elucidate the intergenerational neurocognitive effects of maternal TBI in animal models and humans. To achieve this goal, we combine the lab’s experimental studies in animal models with artificial intelligence to analyze human data.

Our techniques

We employ a wide spectrum of techniques from epigenomics, transcriptomics, bioinformatics, immunofluorescence, protein quantification, patch-clamp electrophysiology, and electroencephalography to different behavioral paradigms in rodents.

Our team

Postdoctoral associates

• Ling-sha (Lisa) Ju, PhD
• Zeeshan A. Khan, PhD
• Cibele C. Castro, PhD

Biological scientists

• Fan Lin, BS
• Caleb Charles, BS

International visiting scholars

• Harini Reddy Choula, MD

Undergrad student volunteers

• Alexander J. Gomez
• Tahiris A. Duran
• Treasure A. Ray
• Carmen F. Yang Su
• Alejandra M. Mantilla
• Lael Thomas
• Sophie Gaer
• Harleen K. Gill
• David J. Sampson
• Deen J. Roylance
• Sebin P. George
• Harleen K. Gill
• Liza Thomas

Anesthesiology faculty involved in our research

• Nikolaus Gravenstein, MD……………..Professor, Anesthesiology
• Tim Morey, MD……………………………..Professor, Anesthesiology

Our collaborators

• Barry Setlow, PhD, Department of Psychiatry, University of Florida
• Paul S. Cooke, PhD, Department of Physiological Sciences, University of Florida
• James L. Resnick, PhD, Department of Molecular Genetics and Microbiology, University of Florida

List of our publications in PubMed

We welcome faculty, residents, medical students, and undergrads who are interested in collaboration, training, or just gaining initial experience in basic science laboratory research.