Heterogeneous propagation of spreading depolarizations in the lissencephalic and gyrencephalic brain

In the recently published article, “Heterogeneous incidence and propagation of spreading depolarizations,” it is shown, in vivo and in vitro, how KCl-induced spreading depolarizations in mouse and rat brains can be highly variable, and that they are not limited, as once thought, to a concentric, isotropic, or homogenous depolarization wave in space or in time. The reported results serve as a link between the different species, and this paper contributes to changing the way in which SD expansion is viewed in the lissencephalic brain. Here, we discuss their results with our previous observations made in the gyrencephalic swine brain, in computer simulations, and in the human brain.

Gabapentin reduces infarct volume but does not suppress peri-infarct depolarizations

Spreading depression (SD) is an intense depolarization wave implicated in brain injury. In focal ischemia, recurrent peri-infarct depolarization (PID) waves akin to SD worsen the ischemic injury by exacerbating the blood flow-metabolism mismatch. We recently showed that gabapentin suppresses SD. We, therefore, tested gabapentin on PIDs and stroke outcome. Gabapentin pretreatment (200 mg/kg, intravenously) reduced the infarct volume by 23% after transient focal ischemia in mice. However, the frequency and duration of PIDs were not suppressed when recorded for 2hours during ischemia, suggesting that gabapentin reduces infarct volume independent of PID suppression.

Gabapentin Suppresses Cortical Spreading Depression Susceptibility

Cortical spreading depression (CSD) is an intense depolarization wave implicated in the pathophysiology of brain injury states and migraine aura. As Cav2.1 channels modulate CSD susceptibility, we tested gabapentin, which inhibits Cav2.1 through high-affinity binding to its α2δ subunit, on CSD susceptibility in anesthetized rats. Gabapentin, 100 or 200 mg/kg, elevated the electrical threshold for CSD and diminished recurrent CSDs evoked by topical KCl, when administered 1 hour before testing. With its favorable safety and tolerability profile, gabapentin may have a role in suppression of injury depolarizations in stroke, intracranial hemorrhage, and traumatic brain injury.