Spreading Depolarizations and Late Secondary Insults after Traumatic Brain Injury

Abstract

Here we investigated the incidence of cortical spreading depolarizations (spreading depression and peri-infarct depolarization) after traumatic brain injury (TBI) and their relationship to systemic physiologic values during neurointensive care. Subdural electrode strips were placed on peri-contusional cortex in 32 patients who underwent surgical treatment for TBI. Prospective electrocorticography was performed during neurointensive care with retrospective analysis of hourly nursing chart data. Recordings were 84 hr (median) per patient and 2,503 hr in total. In 17 patients (53%), 280 spreading depolarizations (spreading depressions and peri-infarct depolarizations) were observed. Depolarizations occurred in a bimodal pattern with peak incidence on days 1 and 7. The probability of a depolarization occurring increased significantly as a function of declining mean arterial pressure (MAP; R(2) = 0.78; p < 0.001) and cerebral perfusion pressure (R(2) = 0.85; p < 0.01), and increasing core temperature (R(2) = 0.44; p < 0.05). Depolarization probability was 7% for MAP values of >100 mm Hg but 33% for MAP of < or =70 mm Hg. Temperatures of < or =38.4 degrees C were associated with a 21% depolarization risk, compared to 63% for >38.4 degrees C. Intracranial pressures were higher in patients with depolarizations (18.3 +/- 9.3 vs. 13.5 +/- 6.7 mm Hg; p < 0.001). We conclude that depolarization phenomena are a common cortical pathology in TBI. Their association with lower perfusion levels and higher temperatures suggests that the labile balance of energy supply and demand is an important determinant of their occurrence. Monitoring of depolarizations might serve as a functional measure to guide therapeutic efforts and their blockade may provide an additional line of defense against the effects of secondary insults.

Pannexin Protein Expression in the Rat Middle Cerebral Artery

“…On the other hand, pannexin hemichannels could be activated during conditions of cellular depolarization such as traumatic brain injury [43], stroke [44] and subarachnoid hemorrhage [45]. Under normal conditions, Panx1 could contribute to the propagation of calcium waves within the vasculature by mediating the release of ATP [18] and as such play an important role in mediating vascular tone.…”

Interplay between Cortical Spreading Depolarization and Seizures

“…These studies have found worse outcomes in patients whose electrocorticography recordings showed the occurrence of CSD following the inciting trauma. Moreover, the presence of CSD correlated with low blood pressure, abnormal cerebral pressure, and fever, all of which have been associated with increased morbidity in trauma patients [23]. …”

Suppression of spreading depolarization and stabilization of dendritic spines by GLYX-13, an NMDA receptor glycine-site functional partial agonist

“…The long-term functional significance of this surprising lability of dendritic spine morphology to cognitive function, and future susceptibility to a range of pathologies from Alzheimer's to epilepsy to migraine, is unknown. However, it seems a reasonable hypothesis that the complete recovery of spine size at their former locations following SD that is promoted by GLYX-13 is likely to be therapeutically beneficial in preventing long-term negative sequelae of migraine, and other generators of SDs such as traumatic brain injury (Hartings et al, 2009(Hartings et al, , 2014Sword et al, 2013), ischemia (Risher et al, 2010) and seizures (Takano et al, 2007).…”