THE ROLE OF CORTICAL SPREADING DEPOLARIZATIONS IN TRAUMATIC BRAIN INJURY OUTCOME

Abstract

Traumatic brain injury (TBI) is a blow to the head that disrupts normal brain function. Concussion is a common clinical syndrome that can follow mild TBI. Concussion is associated with a variety of disabling neurological symptoms that may last for months and even years. Despite growing interest in understanding the pathophysiology of concussion, the electrophysiological events that occur during mild TBI and underlie concussion are unknown.

To investigate the electrophysiological changes underlying concussion, we recorded epidurally from rats immediately following mild TBI. We confirmed that spreading depolarizations (SDs), and not seizures, are a common event after a mild TBI, and mostly occur within the first two minutes after an impact in one or both brain hemispheres. Animals with SDs required a longer time to resume mobility. Furthermore, TBI-induced SDs have a larger amplitude compared to triggered SDs in anesthetized and unanesthetized animals.

Next, we used intravital microscopy to study the effect of triggered SDs on blood-brain barrier (BBB) integrity and neurovascular coupling. TBI-exposed animals (but not control) showed a significant increase in BBB permeability within two hours after stimulation. The cerebral blood flow response to SDs in TBI-exposed rats was similar to that recorded in controls except the late hyperemia phase, which was significantly shorter in TBI.

To study sudden death in this TBI model, we recorded the electrical activity from the cortical hemispheres and brain stem. Within two minutes of impact, we observed SDs and non-spreading depression of electrical activity in both brain hemispheres and the brain stem. Respiration gradually slowed and eventually ceased when a depression of electrical activity was longer than 2 minutes. Cardiac arrest followed respiratory arrest and occurred around 18 minutes after TBI.

In summary, depression of brain activity is a common immediate electrophysiological change following mild TBI and may underlie signs and symptoms of concussion and be associated with immediate catastrophic death. My study proposes SD as a potential diagnostic and therapeutic target in TBI.