Helen M. Bramlett, Ph.D.

The Pathophysiology and Treatment of CNS Injury

The main focus of my laboratory is investigating the pathophysiology of traumatic injury leading to the use of therapeutic strategies targeting specific mechanisms of damage. My laboratory focuses on three areas of traumatic research: 1) the use of therapeutic hypothermia after injury and disease, 2) novel cell-derived treatments for CNS injury and 3) the impact of nicotine on recovery after stroke or traumatic brain injury (TBI).

Our laboratory has been investigating the therapeutic potential of hypothermia for many years. Current studies are involved in clarifying the importance of targeted temperature management and inflammatory markers of secondary brain injury. Models of focal as well as diffuse brain injury are being used to investigate strategies for improving outcomes and reducing vulnerability patterns to secondary insults. We have previously shown that therapeutic hypothermia reduces blood brain barrier breakdown as well as diffuse axonal injury. Most recently, we have determined that hypothermia also modulates the innate immune response through reducing inflammasome activation and subsequent caspase-1 production. We are currently investigating the use of nanodrugs that target temperature receptors in the brain to demonstrate efficacy in our models of traumatic brain injury and stroke.  Our long-term goal is to develop these therapies and translate them to the clinic.

Our laboratory and others have been studying the use of cell-derived extracellular vesicles or exosomes to provide neuroprotection after CNS injury.   Current studies in the laboratory are designed to determine what cell-derived EVs or exosomes provide the most robust improvement in reducing secondary injury mechanisms and behavior.  This treatment was approved for a single study of an ALS patient and therefore once efficacy is demonstrated in our models, we can eventually translate their use to other injuries or disease in the clinic.

Another area of active investigation includes the impact that smoking can have on outcomes after stroke or traumatic brain injury.  We have an active collaboration on this project with Dr. Ami Raval in the Neurology Department.  We use multiple outcomes to assess the impact of nicotine exposure after stroke or TBI on not only secondary injury mechanisms but also treatments that can be used to combat the detrimental consequences of smoking.