Modeling Focal Cerebral Ischemia in Rodents: Introduction and Overview
The chapter provides an introduction and overview on the most widely used rodent models of focal cerebral ischemia, pointing out the major characteristics of the respective model and the basic differences between models. The specific models will be discus
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1. Introduction Cardio- and cerebrovascular diseases are among the principal causes of mortality worldwide, with stroke following second after coronary heart disease (1). However, mortality data conceal the true burden of stroke, as stroke is the number one cause of longterm disability in adulthood and exerts a tremendous socioeconomic impact (1, 2). In the US, the direct and indirect costs have been estimated to consume about $62.7 billion per year (American Heart Association 2007) (3). In Asia, stroke is even more frequent than myocardial infarction. Similarly, epidemiological evidence has demonstrated that cerebrovascular events are becoming more frequent than coronary vascular events (45% and 42%, respectively) in Europe as well. The relative incidence of cerebrovascular events compared with coronary events was 1.19 (95% CI, 1.06–1.33) overall (4). Because of the increasing life expectancy and elderly population, not only in industrialized but also in developing countries, the incidence of stroke is predicted to rise dramatically within the next few decades (1, 5). Ischemic stroke Ulrich Dirnagl (ed.), Rodent Models of Stroke, Neuromethods, vol. 47, DOI 10.1007/978-1-60761-750-1_3, © Springer Science+Business Media, LLC 2010
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accounts for 80% of all strokes, while the incidence of primary hemorrhagic stroke is relatively low. Ischemic stroke probably is and will continue to be one of the most challenging diseases worldwide, underscoring the importance of further research in this field.
2. Cerebral Metabolism Cerebral metabolism depends exclusively on oxygen and glucose, putting the brain into a unique and highly perilous situation compared to other organs. The brain consumes up to 75 l of molecular oxygen and 120 g of glucose daily. Although the brain accounts for only 2% of the total body weight, cerebral metabolism demands 20% of the total oxygen consumption and 20% of the total body perfusion. Even a short period of brain ischemia may result in irreversible structural damage. Variable “ischemia thresholds”, which are region and cell type specific, determine whether a cell will survive the ischemic insult or die (see Table 1). “Ischemic preconditioning” might play a role in this context as well (6).
3. Global Versus Focal Ischemia There are two modes of cerebral ischemia, each with its own distinct mechanisms: global and focal ischemia (see also Table 2). Global ischemia develops after transient circulatory arrest with resuscitation or after near-drowning. Within seconds, absolute cerebral blood flow is reduced from 8 to 0 ml/g/min. Loss of consciousness follows within 10 s, and EEG activity ceases after 30–40 s. Only a few minutes of global cerebral ischemia can cause irreversible cellular damage that becomes histologically apparent over days.
Table 1 Viability thresholds during cerebral ischemia The following perfusion thresholds (ml/g/min) will result in Loss of protein synthesis
0.55
Anaerobic glycolysis
0.35
Synaptic release of transmitters (e.g., glutamate)
0.20
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