Incidence, hemodynamic, and electrical characteristics of spreading depolarization in a swine model are affected by local but not by intravenous application of magnesium

Abstract

The aim was to characterize the effects of magnesium sulfate, using i.v. bolus and local administration, using intrinsic signal imaging, and on electrocorticographic activity during the induction and propagation of spreading depolarizations in the gyrencephalic porcine brain. Local application of magnesium sulfate led to a complete inhibition of spreading depolarizations. One hour after washing out the topical magnesium sulfate, re-incidence of the spreading depolarizations was observed in 50% of the hemispheres. Those spreading depolarizations showed attenuation in hemodynamic characteristics and speed in intrinsic optical signal imaging. The electrical amplitude decreased through electrocorticographic activity. Intravenous magnesium therapy showed no significant effects on spreading depolarization incidence and characteristics.

Spreading Depolarizations Occur in Mild Traumatic Brain Injuries and Are Associated with Postinjury Behavior

“…The impact induced SDs on average propagated at 3.5 mm/min (Fig. 4 M ), which is well within the published range of 2–6 mm/min across tissue and species (Gorelova and Bures, 1983; Guedes and Barreto, 1992; Martin et al, 1994; Aitken et al, 1998; Oliveira-Ferreira et al, 2010; Santos et al, 2016).…”

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

“…In contrast, an intravenous application did not alter SD, which indicates that the blood-brain permeability, high renal elimination, and low bioavailability need to be considered when examining magnesium's therapeutic potential against SD. 114 The same principle can be applied for most therapeutic agents.…”

“…More precisely, the table reveals that the number of SD is the most successful target (as evidenced in 36 articles), 12,40,41,62,63,66–68,88–117 whereas an inhibitory effect on amplitude has only been described in nine articles. 62,89,90,93,105,107,109,110,114 The threshold has only been under scrutiny in experiments, in which SD is electrically induced and was successfully increased in all of them. 63,91,97,118…”

Heterogeneous propagation of spreading depolarizations in the lissencephalic and gyrencephalic brain

“…The first SD seems to be different from the subsequent SDs in the lissencephalic brain, according to Kauffmann et al This confirms previous observations. 16,17 In the supplementary material of our recent paper, 18 we also report differences between the first and later SDs. Again, the mathematical principles of pattern formation can explain a wide range of behaviors.…”