Cortical spreading depression

Cortical spreading depression (CSD) is a wave of electrophysiological hyperactivity followed by a period of neural silence, which is observed in the brain's cortex. This phenomenon is characterized by a slow-moving wave of depolarization followed by a suppression of brain activity. It is believed to play a key role in various neurological conditions, including migraine with aura, stroke, and traumatic brain injury. Understanding CSD is crucial for developing treatments for these conditions.

Overview

Cortical spreading depression involves a dramatic shift in the ionic gradient across the neuronal membranes in the cortex, leading to a temporary loss of membrane potential and cessation of normal brain activity in the affected area. This process is initiated by a variety of factors, including metabolic stress, neuroinflammation, and direct cortical trauma. The wave of depolarization typically spreads across the cortex at a rate of 2-5 mm/min.

Mechanism

The mechanism of CSD involves a complex interplay of ionic fluxes, particularly of potassium ions (K+) and glutamate, an excitatory neurotransmitter. An initial influx of calcium ions (Ca2+) into neurons triggers the release of glutamate, which then further depolarizes neighboring neurons. This leads to an efflux of K+ from neurons into the extracellular space, exacerbating the depolarization wave. The massive neuronal depolarization also disrupts the normal function of the Na+/K+ ATPase pump, which is responsible for maintaining the resting membrane potential, leading to a sustained period of neuronal silence following the wave of depolarization.

Clinical Significance

CSD is most commonly associated with migraine with aura. In this condition, the wave of depolarization is thought to correspond with the aura phase, preceding the headache phase. Moreover, CSD is implicated in the pathophysiology of stroke and traumatic brain injury, where it can contribute to the expansion of lesion size and exacerbate neurological damage.

Research and Treatment

Research into CSD has led to the development of various therapeutic strategies aimed at mitigating its effects, particularly in the context of migraine. Drugs that stabilize neuronal membrane potential or inhibit excessive glutamate release have shown promise in reducing the frequency and severity of migraine attacks. Additionally, understanding the role of CSD in stroke and traumatic brain injury opens up new avenues for neuroprotective interventions that could limit brain damage following these events.

Conclusion

Cortical spreading depression represents a fundamental neurophysiological process with significant implications for a range of neurological conditions. Ongoing research into its mechanisms and effects continues to shed light on the complex dynamics of neuronal activity in the cortex and offers hope for new treatments for conditions like migraine, stroke, and traumatic brain injury.

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  Cortical spreading depression
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  Santos E et al Neuroimage 2014
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  Middle Cerebral Artery occlusion, Kentar et al Acta Neuroch 2020