Cortical Spreading Depression

Definition

Cortical spreading depression (CSD) is a wave of depolarization that slowly propagates across the cerebral cortex, temporarily disrupting normal neuronal activity. This phenomenon is closely linked to the pathophysiology of migraine headaches and serves as a key target for migraine headache drugs.

5 Must Know Facts For Your Next Test

1. Cortical spreading depression is characterized by a wave of depolarization that travels across the cerebral cortex at a rate of 2-5 mm per minute, temporarily disrupting normal neuronal activity.
2. The depolarization wave is associated with a temporary increase in extracellular potassium, a decrease in extracellular calcium, and the release of various neuroactive substances, such as glutamate and nitric oxide.
3. Cortical spreading depression is believed to be a key event in the pathogenesis of migraine with aura, as the propagation of the depolarization wave across the cortex corresponds to the development of the migraine aura.
4. The disruption of normal neuronal activity during cortical spreading depression can lead to the activation of the trigeminovascular system, which is responsible for the generation of migraine pain.
5. Migraine headache drugs, such as triptans and calcitonin gene-related peptide (CGRP) antagonists, are thought to exert their therapeutic effects by modulating the underlying mechanisms of cortical spreading depression and the subsequent activation of the trigeminovascular system.

Review Questions

• Explain the relationship between cortical spreading depression and the pathophysiology of migraine headaches.
  • Cortical spreading depression is closely linked to the development of migraine with aura. The wave of depolarization that propagates across the cerebral cortex during CSD corresponds to the transient neurological symptoms experienced during the aura phase of a migraine. This disruption in normal neuronal activity can then lead to the activation of the trigeminovascular system, which is responsible for the generation of migraine pain. Understanding the role of CSD in the migraine pathophysiology has been crucial for the development of targeted migraine therapies.
• Describe the physiological changes that occur during cortical spreading depression and how they contribute to the migraine process.
  • During cortical spreading depression, there is a wave of depolarization that travels across the cerebral cortex, accompanied by an increase in extracellular potassium, a decrease in extracellular calcium, and the release of various neuroactive substances, such as glutamate and nitric oxide. These physiological changes temporarily disrupt normal neuronal activity, which can then trigger the activation of the trigeminovascular system. The activation of this sensory network innervating the blood vessels and meninges of the brain leads to the generation of migraine pain. The understanding of these underlying mechanisms has been crucial for the development of migraine-specific treatments that target the pathways involved in cortical spreading depression.
• Analyze the role of cortical spreading depression in the development of migraine headache drugs and explain how these drugs may modulate the underlying mechanisms of CSD.
  • Cortical spreading depression is a key target for the development of migraine-specific treatments, as it is a central event in the pathogenesis of migraine with aura. Drugs like triptans and CGRP antagonists are believed to exert their therapeutic effects by modulating the underlying mechanisms of CSD and the subsequent activation of the trigeminovascular system. For example, triptans may act by inhibiting the propagation of the depolarization wave during CSD, while CGRP antagonists may block the release of CGRP, a key mediator of migraine pain. By understanding the role of CSD in the migraine process, researchers have been able to develop more targeted and effective therapies for migraine management, focusing on the modulation of the neurophysiological changes associated with this phenomenon.

Related terms

Neuronal Excitability: The ability of neurons to generate and transmit electrical signals, which can be modulated by various factors and is altered during cortical spreading depression.

Aura: The transient neurological symptoms, such as visual disturbances, that precede the onset of a migraine headache and are associated with the propagation of cortical spreading depression.

Trigeminovascular System: The network of sensory nerves, including the trigeminal nerve, that innervate the blood vessels and meninges of the brain and are involved in the generation of migraine pain, which can be triggered by cortical spreading depression.