Simulation of spreading depolarization trajectories in cerebral cortex: Correlation of velocity and susceptibility in patients with aneurysmal subarachnoid hemorrhage

Abstract

In many cerebral grey matter structures including the neocortex, spreading depolarization (SD) is the principal mechanism of the near-complete breakdown of the transcellular ion gradients with abrupt water influx into neurons. Accordingly, SDs are abundantly recorded in patients with traumatic brain injury, spontaneous intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage (aSAH) and malignant hemispheric stroke using subdural electrode strips. SD is observed as a large slow potential change, spreading in the cortex at velocities between 2 and 9 mm/min. Velocity and SD susceptibility typically correlate positively in various animal models. In patients monitored in neurocritical care, the Co-Operative Studies on Brain Injury Depolarizations (COSBID) recommends several variables to quantify SD occurrence and susceptibility, although accurate measures of SD velocity have not been possible. Therefore, we developed an algorithm to estimate SD velocities based on reconstructing SD trajectories of the wave-front's curvature center from magnetic resonance imaging scans and time-of-SD-arrival-differences between subdural electrode pairs. We then correlated variables indicating SD susceptibility with algorithm-estimated SD velocities in twelve aSAH patients. Highly significant correlations supported the algorithm's validity. The trajectory search failed significantly more often for SDs recorded directly over emerging focal brain lesions suggesting in humans similar to animals that the complexity of SD propagation paths increase in tissue undergoing injury.

Terminal spreading depolarization and electrical silence in death of human cerebral cortex

“…7 Failure of the energy-dependent recovery under continued oxygen and glucose depletion is the most obvious discriminator between SD in ischemic and normal tissue. 37 Accordingly, the negative DC shift of SD becomes one of indefinite duration under anoxia-severe ischemia. However, anoxia-triggered SD is fully reversible without any signs of cellular damage, if the oxidative substrate supply is reestablished before the so-called commitment point, defined as the time when neurons start dying under persistent depolarization.…”

The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex

“…Spreading depolarizations (SDs) play an important role in this concept because they are indicators of disturbed energy metabolism and propagate widely from ischaemic or metabolically stressed zones in both animals and humans, thereby affording even remote detection of newly developing injury ( Hartings et al , 2017 c ). Previous animal experiments and human case reports moreover suggest that their local characteristics inform whether a given electrode is positioned either (i) directly at; (ii) in the neighbourhood of; or (iii) remote from a newly developing ischaemic zone ( Oliveira-Ferreira et al , 2010 ; Dreier et al , 2017 ; Hartings et al , 2017 b ; Milakara et al , 2017 ; Winkler et al , 2017 ).…”

Spreading depolarizations in the rat endothelin-1 model of focal cerebellar ischemia

“…All previous studies on the brain-topical ET-1 model have been performed in neocortex, which is characterized by (i) high vulnerability of the pyramidal cells in layers III, IV and V 26,27 and (ii) relatively high susceptibility to SD compared to other gray matter structures. [28][29][30] In order to answer the above question, we decided to investigate a gray matter structure in the current study, which contains highly vulnerable neurons to ischemia, but has a low susceptibility to SD. These conditions apply to the cerebellar cortex, in which some of the most vulnerable neurons, the Purkinje cells, are located.…”