title: Pharmacological modulation of spreading depolarizations.
abstract: Spreading depolarization (SD) is a wave of almost complete depolarization of the neuronal and glial cells. Nowadays there is sufficient evidence demonstrating its pathophysiological effect in migraine with aura, transient global amnesia, stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. In these cases, occurrence of SD has been associated with functional neuronal damage, neuronal necrosis, neurological degeneration, and poor clinical outcome. Animal models show that SD can be modulated by drugs that interfere with its initiation and propagation. There are many pharmacological targets that may help to suppress SD occurrence, such as Na⁺, K⁺, Cl⁻, and Ca²⁺ channels; Na⁺/K⁺ -ATPase; gap junctions; and ligand-based receptors, for example, adrenergic, serotonin, sigma-1, calcitonin gene-related peptide, GABAA, and glutamate receptors. In this regard, N-methyl-d-aspartate (NMDA) receptor blockers, in particular, ketamine, have shown promising results. Therefore, theoretically pharmacologic modulation of SD could help diminish its pathological effects.
authors.affiliation: Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany, renan.sanchez-porras@med.uni-heidelberg.de.
authors.forename: Renán
authors.initials: R
authors.lastname: Sánchez-Porras
authors.forename: Zelong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
mesh_terms: D020236:Amnesia, Transient Global / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D007649:Ketamine / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine