The Use of Animal Models for Stroke Research: A Review

Mouse models of stroke


Stroke is a focal neurologic deficit caused by an alteration in circulation in the encephalon. In the last decade, this term has evolved to include injuries caused by hemodynamic disturbances and coagulation that cannot be detected in arteries or veins.70 Stroke is one of the most prevalent pathologies affecting the CNS. Recent studies indicate that stroke has become the second most common cause of death. Stroke is important for public health reasons because it is the main cause of physical and cognitive incapacities in developing countries.30,12,33 In 2001, stroke was responsible for 5.5 million deaths and 15 million nonlethal brain injuries worldwide; these figures are projected to increase to 6.3 million deaths in 2015 and 7.8 million in 2030.46,67 Stroke lethality is 11% in women and 8.4% in men and is more prevalent among blacks than whites, especially in the younger age groups.45

Of all strokes, 88% are ischemic, 9% involve an intracerebral hemorrhage, and 3% involve a subarachnoid hemorrhage. The most common type of stroke is atherothrombotic brain infarction, which accounts for approximately 61% of all strokes (excluding transient ischemic attacks). The second most common type of stroke is embolic stroke, at 22%.66 Most stroke survivors develop lasting symptoms, such as physical and intellectual limitations, leading to high social costs.

Encephalic vascular accident (EVA) is the newest terminology used to describe stroke, replacing the previous nomenclature of ‘cerebrovascular accident.’56 EVA occurs in 4 different forms: 1) ischemic and transitory, with decreased blood flow and possible recovery after 24 h; 2) ischemic and complete, with neurologic deficits caused by a vascular disturbance for one day or more that remains stable; 3) progressive, with intermittent increases in deficits caused by embolisms or thrombus and 4) hemorrhagic, with ruptured vessels and blood overflow caused by increased intracranial pressure. The main risk factors of EVA are hypertension, obesity, smoking, sedentary lifestyle, stress, and high cholesterol.1

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In ischemic EVA, an interruption in cellular oxidative metabolism decreases phosphate and glucose production, liberates neurotransmitters, and decreases levels of calcium and sodium. These factors lead to a reduction in neuronal metabolism and mitochondrial function, energetic insufficiency, formation of arachidonic acid, prostaglandin and leukotrienes, vasoconstriction, plate aggregation and poor microvasculature.15,26,29,44 In hemorrhagic cerebrovascular accidents or EVA, an expansive, acute lesion forms that leads to the destruction, compression, and displacement of encephalic structures; a secondary ischemic lesion around the hematoma may also occur.15,26,29,44

The pathophysiology of cerebral ischemia has been studied in animals with various forms of ischemic lesions. These models have shown that metabolic alterations in reperfusion may lead to cellular lesions in specific brain regions, depending on the duration of the ischemia.15,26,29,44 Regional destruction of the brain is followed by alterations in motor activity.63 Recovery processes begin immediately after the lesion and last for months.63 Even though the recovery process begins gradually after development of the lesion, the motor function present before the lesion will not necessarily be recovered. However, residual functional mechanisms may adapt, demonstrating neuronal plasticity.63

The principal arteries affected by stroke and their clinical symptoms are shown in Figure 1. Clinically, several deficiencies are possible, including deficits in motor function, sensitivity, perception, and language skills. Motor deficiencies are characterized by paralysis (hemiplegia) or weakness (hemiparesis) on the side of the body opposite the lesion. Strokes vary from mild to serious, and the consequences can be either temporary or permanent.53