Cortical spreading depolarizations: Pathophysiology and clinical implications

Abstract

ABSTRACT: A cortical spreading depolarization consists on a sudden, transient, generally lessive and self-propagating wave of sustained depolarization in neurons and glia, which silences their function, due to a near-complete break-down of the transmembrane ionic gradients generated mainly by the Na+/K+-ATPase activity and ion-specific non-gated channels. It self-propagates through the cerebral grey matter, without respecting functional or vascular divisions, causing a depression in spontaneous cerebral activity and inducing an inverse vasoconstrictive hemodynamic response. Genysis of the CDS consists on either mechanical or neurochemical stimulus. CDS are observed in clinical frames where we find oxigen, glucose and other metabolites deficit such as cranioencephalic trauma, subarachnoid hemorrhage, intracerebral hemorraghage, stroke (e.g. malignant hemispheric stroke) or migraine aura. It’s been also linked to epilepsy. The gold-standard to register spreading depolarizations and associated electric events is the electrocorticography with subdural electrodes. The hallmark evidence of CDS in this exam is the negative direct current (DC) shift. CDS are potentially reversible, but if the metabolic impairment persists too long they ignite the cascade to neuronal death. The more its number and longer, the worse the outcome. Specific targeted drugs aiming to this process present as a great promise for stopping CSD-related consecuences such as infarct expansion and cytotoxic edema.