Cortical spreading depression

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Federal government websites often end in. The site is secure. Cortical spreading depression CSD and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow CBF. There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders.

Cortical spreading depression

Metrics details. Spreading depression SD is a slowly propagating wave of near-complete depolarization of neurons and glial cells across the cortex. SD is thought to contribute to the underlying pathophysiology of migraine aura, and possibly also an intrinsic brain activity causing migraine headache. Experimental models of SD have recapitulated multiple migraine-related phenomena and are considered highly translational. In this review, we summarize conventional and novel methods to trigger SD, with specific focus on optogenetic methods. We outline physiological triggers that might affect SD susceptibility, review a multitude of physiological, biochemical, and behavioral consequences of SD, and elaborate their relevance to migraine pathophysiology. The possibility of constructing a recurrent episodic or chronic migraine model using SD is also discussed. SD is characterized by a profound change in transmembrane ion gradients and loss of all spontaneous or evoked synaptic activity and action potentials, resulting in depression of electrocortical signals [ 2 ]. Since the original publications of Leao [ 1 , 7 ], experimental SD has been recorded in the cortices of both lissencephalic e. A link between SD and migraine pathogenesis has been hypothesized for decades [ 12 ], in particular the visual aura [ 13 , 14 ] and more recently the migraine headache. The visual disturbance can be variable and include fortification spectra, sparkling or shimmering colored dots and blobs, and scotoma [ 15 , 16 , 17 ]. While visual symptoms are the most commonly described aura event of migraine, other auras including sensory and speech disturbance have been described. In those with more than one aura symptom, the onset of the second or third aura symptom seem to follow the first or second aura symptom in succession, i.

Exp Neurol 97 2 — Waldie, K.

Metrics details. A Correction to this article was published on 20 December There is increasing evidence from human and animal studies that cortical spreading depression CSD is the neurophysiological correlate of migraine aura and a trigger of migraine pain mechanisms. The mechanisms of initiation of CSD in the brain of migraineurs remain unknown, and the mechanisms of initiation of experimentally induced CSD in normally metabolizing brain tissue remain incompletely understood and controversial. Here, we investigated the mechanisms of CSD initiation by focal application of KCl in mouse cerebral cortex slices.

Federal government websites often end in. The site is secure. Since its original extensive description by Leao in , thousands of publications have characterized the phenomenon of cortical spreading depression CSD. Despite the attention that CSD has received over more than six decades, however, many fundamental questions regarding its initiation, propagation, functional consequences, and relationship to migraine and other human disorders remain unanswered. Advances in genetics and cellular imaging have led to important insights into the basic mechanisms of CSD, with increasing attention focused on specific neuronal ion channels, neurotransmitters and neuromodulators. In addition, there is growing recognition that astrocytes and the vasculature may play an active, rather than simply a passive or reactive role in CSD.

Cortical spreading depression

Metrics details. Spreading depression SD is a slowly propagating wave of near-complete depolarization of neurons and glial cells across the cortex. SD is thought to contribute to the underlying pathophysiology of migraine aura, and possibly also an intrinsic brain activity causing migraine headache. Experimental models of SD have recapitulated multiple migraine-related phenomena and are considered highly translational. In this review, we summarize conventional and novel methods to trigger SD, with specific focus on optogenetic methods. We outline physiological triggers that might affect SD susceptibility, review a multitude of physiological, biochemical, and behavioral consequences of SD, and elaborate their relevance to migraine pathophysiology. The possibility of constructing a recurrent episodic or chronic migraine model using SD is also discussed. SD is characterized by a profound change in transmembrane ion gradients and loss of all spontaneous or evoked synaptic activity and action potentials, resulting in depression of electrocortical signals [ 2 ]. Since the original publications of Leao [ 1 , 7 ], experimental SD has been recorded in the cortices of both lissencephalic e.

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Table 1 Symptoms of migraine with aura. Migraine with aura; Hemiparesis; Seizures; Memory loss; Coma. In-vitro models of SD In vivo models can be challenging and time consuming due to microsurgical preparation and maintenance of stable systemic physiological conditions under anesthesia. USA , — Provided by the Springer Nature SharedIt content-sharing initiative. The calibration bar of trace 4 also applies to trace 3 and that of trace 6 also applies to trace 5. However, in the case of a stroke the symptoms are new for the person. Migraine and stroke. Spreading depression: from serendipity to targeted therapy in migraine prophylaxis. CSD may underlie such microdialysis markers of disturbed metabolism Parkin et al , ; Hartings et al , , as PIDs cause cumulative depletion of glucose and accumulation of lactate Hopwood et al , Laudon, Putaala J. Largo, C.

Wannan Tang and Gry Fluge Vindedal contributed equally to this work. Looger, Erlend A. Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity.

Other monogenic syndromes, such as retinal vasculopathy with cerebral leukodystrophy RVCL , cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CADSIL may give some molecular insight into the patho-physiology of migraine. We shall, however, present the evidence that a clear distinction needs to be made between spreading depolarizations 1 that are accompanied by spontaneously reversible recovery of normal function and 2 PIDs—accompanied by prolonged recovery of cortical function, or no recovery at all. Pathophysiology of the migraine aura. Malignant Hemispheric Stroke Transient elevations of extracellular potassium resembling CSD were demonstrated as early as in a baboon focal ischemia model Branston et al , , and not much later, CSD-like depolarizations were described in stroke models in cats Strong et al , and rats Nedergaard and Astrup, The triggering of spreading depression in the chicken retina: a pharmacological study. The upper half of the figure shows the normal hemodynamic response to spreading depolarization CSD in the human brain in a patient with aSAH. Prodrome is the beginning of a migraine attack occurring few days or few hours before the migraine. Zhao J, Levy D Modulation of intracranial meningeal nociceptor activity by cortical spreading depression: a reassessment. Spreading depression expands traumatic injury in neocortical brain slices. Largo, C. PMID The CSD or disturbances of the hemodynamic response to CSD are potentially amenable to therapy, which raises an important issue regarding protection of vulnerable nerve cells based on new therapeutic strategies. Tfelt-Hansen, P. Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex.