Cortical spreading depression (CSD) or spreading depolarization (SD) is a wave of

electrophysiological Electrophysiology (from ee the Electron#Etymology, etymology of "electron" ; and ) is the branch of physiology that studies the electrical properties of biological cell (biology), cells and tissues. It involves measurements of voltage change ...

hyperactivity followed by a wave of inhibition. Spreading depolarization describes a phenomenon characterized by the appearance of depolarization waves of the

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

and

neuroglia Glia, also called glial cells (gliocytes) or neuroglia, are non- neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

that propagates across the

cortex Cortex or cortical may refer to: Biology * Cortex (anatomy), the outermost layer of an organ ** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain'' *** Motor cortex, the regions of the cerebral cortex i ...

at a velocity of 1.5–9.5 mm/min. CSD can be induced by hypoxic conditions and facilitates neuronal death in energy-compromised tissue. CSD has also been implicated in migraine aura, where CSD is assumed to ascend in well-nourished tissue and is typically benign in most cases, although it may increase the probability in

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

patients to develop a

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

. 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) refers to the sudden, unexpected death of a person with epilepsy that is not the result of trauma, drowning, or an identified medical condition. In most cases, no structural or toxicological cause of d ...

, by way of ion channel mutations such as those seen in

Dravet syndrome Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures o ...

, a particularly severe form of childhood epilepsy that appears to carry an unusually high risk of SUDEP (sudden unexpected death in epilepsy). Although the terms cortical spreading depression and spreading depolarization are often used as synonyms, a study found spreading depolarizations can produce variable effects on cortical activity in humans and rats, ranging from depressed to booming activity depending on SD depth.

Uses of the term

Neuroscientist A neuroscientist (or neurobiologist) is a scientist specializing in neuroscience that deals with the anatomy and function of neurons, Biological neural network, neural circuits, and glia, and their Behavior, behavioral, biological, and psycholo ...

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 (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

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. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

. * 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 vesse ...

following

vasodilation Vasodilation, also known as vasorelaxation, 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. Blood vessel wa ...

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 Geographic contiguity is t ...

cortical

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

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), ...

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

potassium ion Potassium is a chemical element; it has symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to form flaky white pot ...

concentration and excitatory

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

contribute to the initiation and propagation of cortical spreading depression, which is the underlying cause of migraine aura. Chronic daily administration of migraine prophylactic drugs (

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

valproate Valproate (valproic acid, VPA, 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 those with ...

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headac ...

, and methysergide) 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-Gastau ...

(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