We seek to understand how the developing brain responds to injury
“All living systems require energy to survive and thrive. Their success or failure is solely determined by whether there is sufficient energy to fuel these processes. What can complicate this intricate balance is injury and the key role of energy. The Scafidi Laboratory is interested in understanding metabolic adaptations after perinatal brain injury in the acute and long-term recovery phase. Specifically, we aim to understand how different cell populations in different brain regions utilize energy after injury, and how these adaptations or maladaptations affect the recovery process. Understanding these processes will allow us to delineate the brain’s innate ability for recovery and develop novel, targeted therapies that will promote neurorehabilitation.” -Dr. Scafidi via KKI
Post-injury metabolism is key to understanding long-term structural and behavioral deficits
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Impact on patients
Preterm birth, traumatic brain injury, and other causes of perinatal hypoxia cause lasting structural deficits to the brain and neurobehavioral impairments, often leading to lifelong cognitive challenges. Understanding how the pediatric brain responds to injury at a cellular level can help identify opportunities to ameliorate outcomes for these children. As clinician-scientists, our experience with patients is at the heart of what we do in the lab and directly informs how we study injury and potential therapeutic options.
Metabolic Disruptions following Traumatic Brain Injury (TBI)
Brain injury during the perinatal period, whether from TBI, preterm birth or hypoxia, alters brain metabolism and often leads to life-long challenges. Immediately post-injury, the brain’s uptake of oxidative glucose is delayed and dysregulated. In response, the injured brain turns to other sources for energy, such as fatty acids. Understanding these changes in response to injury can elucidate pathways to restoring brain function.
Glucose and beyond
Glucose is the primary source of energy in the healthy brain, but following injury, oxidative glucose metabolism is dysregulated. Remarkably, the infant brain is flexible, switching to alternative substrates for energy. While we have substantial research on glucose patterns, these alternative substrates are less understood but may provide an opportunity for intervention.
A window of opportunity
The perinatal period is a time of immense development in a young infant’s brain, thus injury can have lasting effects on their lives. Importantly, the period immediately following injury is particularly sensitive and provides an opportunity to intervene. We know that in this time period, many processes, such as oxidative glucose metabolism, are impaired, and that the brain turns to alternative substrates such as fatty acids.
Beyond understanding the effects of injury, our research also aims to investigate how we can intervene in the critical window immediately following injury to limit damage to the brain. Our research finds that efforts such as boosting EGFR signaling and administering acetyl-L-carnitine can improve outcomes in animal models.
Our research approaches
Our lab uses a multi-disciplinary research strategy encompassing a variety of approaches, including molecular biology and genetics, cellular neurobiology, and biochemical assays. We use both in-vivo rodent and ex-vivo rodent and human models understand the brain’s mechanisms. Our neuroimaging techniques include MR spectroscopy and functional imaging. Finally, we perform neurobehavioral testing throughout development to understand brain function.
Scafidi Lab 