S04: Spreading Depolarizations as a Mechanistic Target in TBI:  Translational Studies

Chair: M. Ross Bullock, PhD

S04.01 - Triggers and Consequences of Spreading Depolarizations in Focal Ischemia

   Cenk Ayata, MD - Massachusetts General Hospital

S04.02 - Spreading Depolarizations in Animal Models of TBI

   Jason Hinzman, PhD - University of Cincinnati

S04.03 - Characteristics and Effects of Spreading Depolarizations in Clinical Severe Brain Trauma

   Jed Hartings, PhD - University of Cincinnati

Session Description

Spreading depolarizations (SD) are the mechanism of abrupt failure of ion homeostasis in the development of acute cortical lesions. In focal ischemia, an initial terminal SD defines the ischemic core, and subsequent spontaneous SDs expand this core region, resulting in time-dependent lesion growth. Historically, these concepts have not translated to traumatic brain injury (TBI) since common rodent models exhibit sparse SD activity, if any. Recent neurointensive monitoring of severe TBI patients, however, has shown that SD is a common mechanism in the human brain, occurring in ~60% of patients with an independent association with worse outcomes. In this symposium, Dr. Cenk Ayata will review basic concepts of SD in relation to ischemic lesion development.  Dr. Jed Hartings will discuss the clinical monitoring of SD and its potential role in real-time diagnosis and treatment of secondary injury. Finally, Dr. Jason Hinzman will present new experimental results that demonstrate a prominent role of SD in the development of cortical lesions in a swine model of cerebral contusion and in a rat model of acute subdural hematoma. This session will be of high interest to clinicians since SD is now the first pathophysiologic mechanism that can be continuously monitored in patients for personalized neurointensive management and as a criterion for patient inclusion in targeted clinical trials. It also has high relevance to neuroscientists since SD affects a wide variety of commonly studied injury mechanisms, including inflammation, glial activation, cerebral blood flow and metabolism, and glutamate excitotoxicity.  

Learning Objectives

At the conclusion of this session, attendees will be able to:

1. Explain the concept of spreading depolarization and its role in ischemic lesion development.
2. Describe the limitations of various TBI models for studying spreading depolarizations. 
3. Explain the methods of monitoring spreading depolarization in TBI patients.
4. Describe the evidence that spreading depolarizations adversely impact recovery from TBI.