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KEY CONCEPTS

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  • Stroke occurs when blood flow to the brain is disrupted and the areas of brain deprived of oxygen die. This can be caused by obstruction or hemorrhage of blood vessels.

  • Loss of oxygenation causes death of neurons through complex processes, which include excitotoxicity, mediated by excessive release of glutamate from damaged neurons, and subsequent increases in intracellular calcium levels and overactivation of calcium-dependent enzymes.

  • Loss of oxygenation also causes neuronal death through the formation of free radicals and through genetically programmed cell death, called apoptosis.

  • Despite increased understanding of the biochemical processes underlying neuronal death, the best therapy for stroke remains rapidly restoring the brain’s blood supply and preventing the formation of clots and emboli.

  • This includes the use of antiplatelet agents such as aspirin and clopidogrel, and oral anticoagulants such as warfarin and dabigatran, as well as thrombolytic agents such as tissue plasminogen activator (tPA), which target different steps of coagulation cascades.

  • Migraine headaches are believed to result from waves of inhibitory neuronal activity called “cortical spreading depression” that stimulate trigeminal nerve endings innervating the brain’s vasculature. This causes release of proinflammatory substances, such as calcitonin gene–related peptide (CGRP), into and around the vessels, resulting in vasodilation and pain.

  • Treatment regimes for migraine headaches typically employ both prophylactic and abortive strategies.

  • The mainstay in abortive treatment is the triptan drugs, such as sumatriptan, which are agonists at serotonin 5HT1B and 5HT1D receptors.

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STROKE

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Vertebrate neurons are exquisitely specialized for the functions they perform. As explained in previous chapters, a single neuron may receive information from and relay information to thousands of other neurons; consequently, the nervous system is capable of remarkably complex functions. Moreover, the brisk flux of ions across neural membranes permits extremely rapid interneuronal signaling. However, this specialization comes at a cost. A tremendous amount of energy is required to maintain ionic gradients across the membranes of the approximately 100 billion neurons that comprise the human brain. Although the brain represents only 2% of the body’s total mass, it uses approximately 20% of the body’s oxygen supply, and blood flow to the brain accounts for about 15% of total cardiac output. Ischemia, or insufficient blood supply, results in oxygen and glucose deprivation and in the buildup of potentially toxic metabolites such as lactic acid and CO2. Interruption of blood flow to the brain can lead to complete loss of consciousness within 10 seconds, the approximate amount of time required to consume the oxygen contained in the brain.

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Stroke occurs on disruption of blood flow to brain tissue caused by obstruction of blood flow or bleeding in the brain (hemorrhage). The exquisite vulnerability of neurons to energy deprivation caused by stroke results in vast medical, economic, and personal costs. In the United States alone, roughly 795,000 strokes occur each year. This equates to an average of one stroke every 40 seconds in the American population. Approximately ...

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