Spreading depression (SD) is the electrophysiological substrate of migraine aura and a potential trigger for headache. Since its discovery by Leão in 1944, SD has transformed from being viewed as an epiphenomenon into a therapeutic target relevant in the pathophysiology of migraine and brain injury. Despite decades of research, the underpinnings of SD are still poorly understood, hampering our efforts to selectively block its initiation and spread. Experimental models have nevertheless been useful to measure the likelihood of SD occurrence (i.e. SD susceptibility) and characterize genetic, physiological and pharmacological modulation of SD in search of potential therapies, such as in migraine prophylaxis and stroke. Here, I review experimental SD susceptibility endpoints and surrogates, and minimum essential model requirements to improve their utility in drug screening. A critical reappraisal of strengths and caveats of experimental models of SD susceptibility is needed to set standards and improve data quality, interpretation and reconciliation.
The influence of different concentrations of volatile anesthetics on the threshold for cortical spreading depression in rats
The role of the autonomic nervous system in mediating pancreatic endocrine responses to arginine in the calf
Strength-duration properties of cathodal pulses eliciting spreading depression in rat cerebral cortex
Infarct rim: effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation
The activities of butyrylcholinesterase and carbonic anhydrase, the rate of anaerobic glycolysis, and the question of a constant density of glial cells in cerebral cortices of various mammalian species from mouse to whale
The minimum volume of depolarized neural tissue required for triggering cortical spreading depression in rat
Intracerebral microdialysis combined with recording of extracellular field potential: a novel method for investigation of depolarizing drugs in vivo
Influence of plasma glucose concentration on rat brain extracellular calcium transients during spreading depression
Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations
Factors influencing the frequency of fluorescence transients as markers of peri-infarct depolarizations in focal cerebral ischemia
Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels
A quantitative analysis of cortical spreading depression events in the feline brain characterized with diffusion-weighted MRI
The effects of anesthetics on cortical spreading depression elicitation and c-fos expression in rats
A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression
Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro
Hypoxia and hypotension transform the blood flow response to cortical spreading depression from hyperemia into hypoperfusion in the rat
Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na+ ion channel blockade
Perfusion pressure-dependent recovery of cortical spreading depression is independent of tissue oxygenation over a wide physiologic range
High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice
Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura
Simultaneous monitoring of tissue PO2 and NADH fluorescence during synaptic stimulation and spreading depression reveals a transient dissociation between oxygen utilization and mitochondrial redox state in rat hippocampal slices
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome mutations increase susceptibility to spreading depression
Effects of NMDA receptor antagonists with different subtype selectivities on retinal spreading depression
The pharmacological control of neuronal excitability in the retinal spreading depression model of migraine
Suppressive effect of chronic peroral topiramate on potassium-induced cortical spreading depression in rats
Reactive oxygen species initiate a metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression
Heterogeneous propagation of spreading depolarizations in the lissencephalic and gyrencephalic brain
Incidence, hemodynamic, and electrical characteristics of spreading depolarization in a swine model are affected by local but not by intravenous application of magnesium
Cortical spreading depolarizations in the postresuscitation period in a cardiac arrest male rat model
Spreading Depolarizations: A Therapeutic Target Against Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
Glial glutamate transporter GLT-1 determines susceptibility to spreading depression in the mouse cerebral cortex.
Vagus nerve stimulation inhibits cortical spreading depression exclusively through central mechanisms
KCl-induced cortical spreading depression waves more heterogeneously propagate than optogenetically-induced waves in lissencephalic brain: an analysis with optical flow tools
Triptans disrupt brain networks and promote stress-induced CSD-like responses in cortical and subcortical areas
Effects of anti-epileptic drugs on spreading depolarization-induced epileptiform activity in mouse hippocampal slices
A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia.
Intravascular Endothelin-1 does not trigger or increase susceptibility to Spreading Depolarizations.
Real-time non-invasive in vivo visible light detection of cortical spreading depolarizations in mice
Brain Injury & Trauma
brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.