] Cortical spreading depression (CSD) or spreading depolarization (SD) is a wave of Electrophysiology, electrophysiological hyperactivity followed by a wave of inhibition. Spreading depolarization describes a phenomenon characterized by the appearance of depolarization waves of the neurons and neuroglia that propagates across the cortex at a velocity of 1.5–9.5 mm/min. CSD can be induced by

hypoxic Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

conditions and facilitates neuronal death in energy-compromised tissue. CSD has also been implicated in

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few ho ...

aura Aura most commonly refers to: * Aura (paranormal), a field of luminous multicolored radiation around a person or object * Aura (symptom), a symptom experienced before a migraine or seizure Aura may also refer to: Places Extraterrestrial * 1488 ...

, where CSD is assumed to ascend in well-nourished tissue and is typically benign in most of the cases, although it may increase the probability in migraine patients to develop a stroke. Spreading depolarization within brainstem tissues regulating functions crucial for life has been implicated in

sudden unexpected death in epilepsy Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy. It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death det ...

, by way of ion channel mutations such as those seen in Dravet syndrome, a particularly severe form of childhood epilepsy that appears to carry an unusually high risk of SUDEP (sudden unexpected death in epilepsy).

Uses of the term

Neuroscientist A neuroscientist (or neurobiologist) is a scientist who has specialised knowledge in neuroscience, a branch of biology that deals with the physiology, biochemistry, psychology, anatomy and molecular biology of neurons, Biological neural network, n ...

s use the term cortical spreading depression to represent at least one of the following cortical processes: * The spreading of a self-propagating wave of cellular

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...

in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

. * The spreading of a wave of

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

passing through an area of cortex. * The spreading of a wave of

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood ve ...

following

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstricti ...

and prolonged sustained

contiguous Contiguity or contiguous may refer to: *Contiguous data storage, in computer science * Contiguity (probability theory) *Contiguity (psychology) * Contiguous distribution of species, in biogeography *Geographic contiguity of territorial land *Conti ...

cortical

arteriole An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have muscular walls (usually only one to two layers of smooth muscle cells) and are the pri ...

s. The

scintillating scotoma Scintillating scotoma is a common visual aura that was first described by 19th-century physician Hubert Airy (1838–1903). Originating from the brain, it may precede a migraine headache, but can also occur acephalgically (without headache), also ...

in humans may be related to the neurophysiologic phenomenon termed the spreading depression of Leão. Increased extracellular

potassium ion Potassium is the chemical element with the symbol K (from Neo-Latin '' kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...

concentration and excitatory

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

contribute to the initiation and propagation of cortical spreading depression, which is the underlying cause of

migraine aura An aura is a perceptual disturbance experienced by some with epilepsy or migraine. An epileptic aura is a seizure. Epileptic and migraine auras are due to the involvement of specific areas of the brain, which are those that determine the symptom ...

. Chronic daily administration of migraine prophylactic drugs (

topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for genera ...

valproate Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in thos ...

propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance a ...

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgia ...

, and

methysergide Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the ma ...

) dose-dependently suppressed frequency of CSD induced by continuous cortical application of 1 M KCl solution. However

lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syn ...

(a drug with specific anti-aura action, but no efficacy in migraine in general) has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin were shown to have no effect on the triggering of cortical spreading depression though they are effective in migraine without aura. Taken together, these results are compatible with a causal role of cortical spreading depression in migraine with aura, but not in migraine without aura. The folded structure of the

is capable of irregular and complex CSD propagation patterns. The irregularities of the folded cortex and the vasculature promote the presence of re-entrance waves, such as spirals and reverberating waves. The expansion of the wave then is less predictable and it is affected by the concentration of different molecules and gradients on the cortex. Its triggers and propagation mechanisms, as well as clinical manifestations of CSD, are a therapeutic target to reduce brain damage after a stroke or brain lesion.

Notes

References

* "Cortical spreading depression causes and coincides with tissue hypoxia", ''Nat Neurosci''. 29 April 2007, Takano T, Tian GF, Peng W, Lou N, Lovatt D, Hansen AJ, Kasischke KA, Nedergaard M., Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York. * "A delayed class of BOLD waveforms associated with spreading depression in the feline cerebral cortex can be detected and characterised using independent component analysis (ICA)", ''Magn Reson Imaging''. 21 November 2003, Netsiri C, Bradley DP, Takeda T, Smith MI, Papadakis N, Hall LD, Parsons AA, James MF, Huang CL., Physiological Laboratory, University of Cambridge, Cambridge, UK. * "Cortical spreading depression (CSD): A neurophysiological correlate of migraine aura", ''Schmerz'', May 17, 2008, Richter F, Lehmenkühler A.

Uses of the term

See also

Notes

References

Further reading