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) neuroprotective strategies for traumatic injury, 2) progressive damage after trauma and 3) secondary injury mechanisms of 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 combining therapeutic hypothermia with a novel proneurogenic compound to promote hippocampal neurogenesis and cognitive function. Our long-term goal is to develop these therapies and translate them into TBI patients.

Our laboratory and others have documented in a clinically relevant model of TBI that there is progressive atrophy of brain structures following injury. However, it is unknown what is causing this continued gray and white matter tissue loss. Is it due to the initial injury or are there active processes ongoing that continue to degrade the tissue? Current studies in the laboratory are designed to determine what mechanisms may be contributing to this progressive damage in order to design appropriate treatment strategies to halt this loss.

Another area of active investigation includes the study of posttraumatic seizure activity as a clinically relevant secondary injury mechanisms. Our laboratory has developed strategies for acute and chronic EEG monitoring to assess both convulsive and nonconvulsive seizure patterns after TBI. Previously, we have reported that hypothermia increases seizure threshold and reduces the frequency and severity of posttraumatic epilepsy. New pharmacological treatments are now being tested to target this clinically relevant consequence of injury.