Xiaowen Bai, MD, PhD, receives NIH R01 to study mechanisms and neuroprotective targets in alcohol-induced brain injury

Fetal alcohol spectrum disorders (FASD) represent a major public health concern in the United States, significantly contributing to intellectual disabilities and abnormal behaviors. Current research shows that people born with alcohol exposure-induced developmental neurotoxicity (AIDN) are born with cells and regions in the brain that experience differential vulnerability to alcohol-induced injury.

Xiaowen Bai, MD, PhD, professor of Anesthesiology in The Ohio State University College of Medicine, just received a five-year, $2.37 million National Institutes of Health R01 award from the National Institute on Alcohol Abuse and Alcoholism. The grant project, titled “Mechanisms and Neuroprotective Targets in Alcohol-Induced Brain Injury,” focuses on identifying key regulators of neuronal injury and mitochondrial dysfunction in alcohol-induced developmental brain injury. The goal is to uncover novel neuroprotective targets and protect neurons that are particularly susceptible to alcohol stress, so that researchers can develop precise interventions.

The study aims to:

• Elucidate brain region-specific and cell-specific mechanisms underlying AIDN on the molecular, cellular, tissue and animal levels, and develop cell-specific precision interventions using mouse models and stem cell-derived human brain tissue.
• Employ innovative, multidisciplinary approaches such as virus-based cell-specific gene modification, spatial transcriptomics, advanced imaging systems and behavioral tests to uncover valuable insights to pave the way for novel treatments.
• Address critical questions, like: Why are neurons more vulnerable to alcohol-induced injury? And, what neuron-specific signaling pathways contribute to this vulnerability?
• Assess the neuroprotective effects of neuron-specific and mitochondria-targeted interventions in AIDN, and identify mechanisms driving alcohol-induced cognitive and behavioral impairments.
• Map out acute and long-term brain region-specific and cell type-specific gene expression profiles following developmental alcohol exposure.
• Develop promising strategies for early, brain cell type-targeted precision interventions and treatments for FASD patients.

Even with a prevalence rate of 1-5% in the United States and the substantial impact it creates, there is currently no cure for FASD. This research could enhance the translational potential of the findings and offer insights applicable to other neurodevelopmental disorders.