Abstract
Spreading depression (SD) is a neurophysiological phenomenon characterized by abrupt changes in intracellular ion gradients and sustained depolarization of neurons. It leads to loss of electrical activity, changes in the synaptic architecture, and an altered vascular response. Although SD is often described as a unique phenomenon with homogeneous characteristics, it may be strongly affected by the particular triggering event and by genetic background. Furthermore, SD may contribute differently to the pathogenesis of widely heterogeneous clinical conditions. Indeed, clinical disorders related to SD vary in their presentation and severity, ranging from benign headache conditions (migraine syndromes) to severely disabling events, such as cerebral ischemia, or even death in people with epilepsy. Although the characteristics and mechanisms of SD have been dissected using a variety of approaches, ranging from cells to human models, this phenomenon remains only partially understood because of its complexity and the difficulty of obtaining direct experimental data. Currently, clinical monitoring of SD is limited to patients who require neurosurgical interventions and the placement of subdural electrode strips. Significantly, SD events recorded in humans display electrophysiological features that are essentially the same as those observed in animal models. Further research using existing and new experimental models of SD may allow a better understanding of its core mechanisms, and of their differences in different clinical conditions, fostering opportunities to identify and develop targeted therapies for SD-related disorders and their worst consequences.
Highlights
Transient brain dysfunctions characterize several neurological disorders, leading to episodic manifestations, e.g., headache or epileptic seizures
The phenomenon self-propagates as a wave in the gray matter by means of contiguity, regardless of functional divisions or arterial territories [1]
It remains incompletely understood due to the complexity of synaptic physiology and the difficulty in obtaining direct experimental data. It is still debated whether the spreading phenomenon should more properly be considered to refer to the depression or to the depolarization, even though the two propagates in the tissue together [3,4,5]
Summary
Transient brain dysfunctions characterize several neurological disorders, leading to episodic manifestations, e.g., headache or epileptic seizures. It remains incompletely understood due to the complexity of synaptic physiology and the difficulty in obtaining direct experimental data It is still debated whether the spreading phenomenon should more properly be considered to refer to the depression or to the depolarization, even though the two propagates in the tissue together [3,4,5]. Some authors use “spreading depolarization” as a generic term indicating the biophysical mechanism underlying the progressive, self-propagating, and near-complete neuronal depolarization [6], and “spreading depression” to refer to the silencing of brain electrical activity, considered a consequence or epiphenomenon of the spreading depolarization. In the present review, the term SD is taken to refer to both spreading phenomena: the propagating depolarization, understood as the initial phenomenon, and the SD proper, understood as its ultimate consequence or epiphenomenon
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