Shih-Pin Chen1,2, Cenk Ayata3,4. 1. Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan. 2. Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Neurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. cayata@mgh.harvard.edu. 4. Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. cayata@mgh.harvard.edu.
Abstract
PURPOSE OF REVIEW: Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient "depression" of all spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy. Here, we provide an overview of the pathogenic mechanisms and propose plausible hypotheses on the involvement of SD in primary and secondary headache disorders. RECENT FINDINGS: SD can activate downstream trigeminovascular nociceptive pathways to explain the cephalgia in migraine, and possibly in secondary headache disorders as well. In healthy, well-nourished tissue (such as migraine), the intense transmembrane ionic shifts, the cell swelling, and the metabolic and hemodynamic responses associated with SD do not cause tissue injury; however, when SD occurs in metabolically compromised tissue (e.g., in ischemic stroke, intracranial hemorrhage, or traumatic brain injury), it can lead to irreversible depolarization, injury, and neuronal death. Recent non-invasive technologies to detect SDs in human brain injury may aid in the investigation of SD in headache disorders in which invasive recordings are not possible. SD explains migraine aura and progression of neurological deficits associated with other neurological disorders. Studying the nature of SD in headache disorders might provide pathophysiological insights for disease and lead to targeted therapies in the era of precision medicine.
PURPOSE OF REVIEW: Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient "depression" of all spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy. Here, we provide an overview of the pathogenic mechanisms and propose plausible hypotheses on the involvement of SD in primary and secondary headache disorders. RECENT FINDINGS:SD can activate downstream trigeminovascular nociceptive pathways to explain the cephalgia in migraine, and possibly in secondary headache disorders as well. In healthy, well-nourished tissue (such as migraine), the intense transmembrane ionic shifts, the cell swelling, and the metabolic and hemodynamic responses associated with SD do not cause tissue injury; however, when SD occurs in metabolically compromised tissue (e.g., in ischemic stroke, intracranial hemorrhage, or traumatic brain injury), it can lead to irreversible depolarization, injury, and neuronal death. Recent non-invasive technologies to detect SDs in humanbrain injury may aid in the investigation of SD in headache disorders in which invasive recordings are not possible. SD explains migraine aura and progression of neurological deficits associated with other neurological disorders. Studying the nature of SD in headache disorders might provide pathophysiological insights for disease and lead to targeted therapies in the era of precision medicine.
Authors: Jed A Hartings; J Adam Wilson; Jason M Hinzman; Sebastian Pollandt; Jens P Dreier; Vince DiNapoli; David M Ficker; Lori A Shutter; Norberto Andaluz Journal: Ann Neurol Date: 2014-09-17 Impact factor: 10.422
Authors: Katharina Eikermann-Haerter; Jeong Hyun Lee; Nilufer Yalcin; Esther S Yu; Ali Daneshmand; Ying Wei; Yi Zheng; Anil Can; Buse Sengul; Michel D Ferrari; Arn M J M van den Maagdenberg; Cenk Ayata Journal: Stroke Date: 2014-11-25 Impact factor: 7.914
Authors: Johannes Woitzik; Nils Hecht; Alexandra Pinczolits; Nora Sandow; Sebastian Major; Maren K L Winkler; Steffen Weber-Carstens; Christian Dohmen; Rudolf Graf; Anthony J Strong; Jens P Dreier; Peter Vajkoczy Journal: Neurology Date: 2013-02-27 Impact factor: 9.910
Authors: Katharina Eikermann-Haerter; Michael J Baum; Michel D Ferrari; Arn M J M van den Maagdenberg; Michael A Moskowitz; Cenk Ayata Journal: Ann Neurol Date: 2009-10 Impact factor: 10.422
Authors: Paula Catirina Germano Magalhães; Ricardo Abadie-Guedes; Manoel Augusto Barbosa da Costa Mendonça; Aline Duarte de Souza; Rubem Carlos Araújo Guedes Journal: Metab Brain Dis Date: 2018-12-13 Impact factor: 3.584
Authors: Olga Cozzolino; Maria Marchese; Francesco Trovato; Enrico Pracucci; Gian Michele Ratto; Maria Gabriella Buzzi; Federico Sicca; Filippo M Santorelli Journal: Front Neurol Date: 2018-02-01 Impact factor: 4.003
Authors: Azize Boström; Dirk Scheele; Birgit Stoffel-Wagner; Frigga Hönig; Shafqat R Chaudhry; Sajjad Muhammad; Rene Hurlemann; Joachim K Krauss; Ilana S Lendvai; Krishnan V Chakravarthy; Thomas M Kinfe Journal: J Transl Med Date: 2019-02-22 Impact factor: 5.531
Authors: Seph M Palomino; Aidan A Levine; Jared Wahl; Erika Liktor-Busa; John M Streicher; Tally M Largent-Milnes Journal: Pharmaceutics Date: 2022-08-10 Impact factor: 6.525
Authors: Karissa E Cottier; Emily A Galloway; Elisa C Calabrese; Margaret E Tome; Erika Liktor-Busa; John Kim; Thomas P Davis; Todd W Vanderah; Tally M Largent-Milnes Journal: eNeuro Date: 2018-07-16