Brainstem and Cortical Spreading Depolarization in a Closed Head Injury Rat Model

Abstract

Traumatic brain injury (TBI) is the leading cause of death in young individuals, and is a major health concern that often leads to long-lasting complications. However, the electrophysiological events that occur immediately after traumatic brain injury, and may underlie impact outcomes, have not been fully elucidated. To investigate the electrophysiological events that immediately follow traumatic brain injury, a weight-drop model of traumatic brain injury was used in rats pre-implanted with epidural and intracerebral electrodes. Electrophysiological (near-direct current) recordings and simultaneous alternating current recordings of brain activity were started within seconds following impact. Cortical spreading depolarization (SD) and SD-induced spreading depression occurred in approximately 50% of mild and severe impacts. SD was recorded within three minutes after injury in either one or both brain hemispheres. Electrographic seizures were rare. While both TBI- and electrically induced SDs resulted in elevated oxidative stress, TBI-exposed brains showed a reduced antioxidant defense. In severe TBI, brainstem SD could be recorded in addition to cortical SD, but this did not lead to the death of the animals. Severe impact, however, led to immediate death in 24% of animals, and was electrocorticographically characterized by non-spreading depression (NSD) of activity followed by terminal SD in both cortex and brainstem.

Spreading depolarization: A phenomenon in the brain

“…Thus, the increase in concentration of K⁺ and glutamate 21,[28][29][30][31] in extracellular space during SDs will cause excitability in neighboring neurons and enhance propagation of SDs to the surrounding tissue across the brain 1,39 . Recently, it has been found that SDs initiated immediately following mild traumatic brain injury (TBI) within around 2 minutes in multisite pattern at the same time 14,40 . The simultaneous arrest of spontaneous brain activity at different brain regions at the same time is describing what is known as nonspreading depression 1,8,10,14,41,42 .…”

“…Recently, it has been found that SDs initiated immediately following mild traumatic brain injury (TBI) within around 2 minutes in multisite pattern at the same time 14,40 . The simultaneous arrest of spontaneous brain activity at different brain regions at the same time is describing what is known as nonspreading depression 1,8,10,14,41,42 . The idea of connecting the term of nonspreading depression to the simultaneous arrest of brain activity is no more can be generalized for all cases, as a simultaneous spreading depolarization of brain activity at different cortical brain regions was recorded in a rodent model of a mild TBI as described previously 14 .…”

“…SDs were previously implicated as the relevant pathological waves propagated across migrainous brain 11 . In 2002, Anthony Strong and colleagues recorded SDs for the first time from human brain following traumatic brain injury (TBI) 12 and intracerebral hemorrhage 13 , and in a rodent model immediately following mild traumatic brain injury 14 . Furthermore, SDs occur abundantly in individuals with aneurismal subarachnoid hemorrhage (ASH), delayed ischemic stroke, subarachnoid hemorrhage (SAH) 5 , and malignant hemispheric stroke 15 .…”

Craniotomy for acute monitoring of pial vessels in the rodent brain

“…In many neurosurgical operations, such of brain tumors [4] , drug resistant epilepsy [3] , intracranial aneurysm and subarachnoid hemorrhage [ 5 , 8 ], a removal of a piece of the skull's bone (craniotomy) is required for accessing the brain directly. In animal research craniotomy is used during in vivo experiments [ 9 , 10 , 2 ], allowing extracellular and intracellular recording of neuronal activity, together with imaging of electrical signaling using fluorescent markers such as voltage sensitive dyes and calcium indicators. In recent years, with the better understanding of the role of other members of the neurovascular unit for normal brain function, including the vascular system and glia cells, new imaging techniques were developed to allow imaging of the cerebro-vasculature, and specifically the integrity of the blood-brain barrier (BBB).…”

Neuroinflammation: The Pathogenic Mechanism of Neurological Disorders

“…In this issue, Aboghazale and colleagues evaluated the electrophysiological alterations of rat brain after traumatic brain injury and have shown the occurrence of both SD and SD-induced depression of cortical activity. Moreover, their findings revealed that while the occurrence of SD following closed brain trauma led to enhanced oxidative stress (elevated reactive oxygen species), traumatic brains exhibited a decreased antioxidant defense (downregulation of mRNA expression of antioxidant enzymes in response to oxidative stress) [ 29 ]. In addition to traumatic brain injury, inflammatory processes play a regulatory role in various mechanisms that result in tissue repair, damage, and/or death following the spinal cord injury (SCI) [ 30 ].…”