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Cytotoxic and Vasogenic Brain Edema

Introduction Cerebral edema is a buildup of fluid in the brain. It occurs after brain ischemia and different types of cerebral hemorrhage, as well as other conditions such as traumatic brain injury and brain neoplasms. It is a major clinical issue. Because of the encasing skull, cerebral edema can cause increased intracranial pressure (ICP), reduced cerebral blood flow, brain herniation and death. Swelling of parenchymal cells…

Pathophysiology of the Peripheral Immune Response in Acute Ischemic Stroke

Acknowledgments This work was supported by the National Institutes of Health grant NS081179. Ischemic stroke triggers an inflammatory response in the affected area, which progresses for days to weeks after the onset of symptoms. The inflammatory reaction involves both tissue resident and peripheral immune cells. Thus the local inflammatory response within the ischemic territory leads to the generation of molecular cues, including cytokines, chemokines and danger-associated…

Central Neuroinflammation in Cerebral Ischemia: The Role of Glia

Introduction Poststroke neuroinflammation contributes to the delayed phase of neuronal cell death in the penumbra following cerebral ischemia . Therefore antiinflammatory strategies that would seek to inhibit the direct effects of inflammation on neuronal homeostasis have been the focus of numerous neuroprotective strategies, with promising results in animal models of ischemic stroke. However, this approach has failed to translate into any measurable clinical utility, and treatment…

Pathophysiology of Ischemic White Matter Injury

Cerebral ischemia is a complex injury process that results in damage to both gray matter and white matter. White matter accounts for up to half of the stroke lesion volume in the central nervous system (CNS), with 20% of strokes being purely in the white matter . White matter is sensitive to ischemia across all developmental ages: perinatal hypoxia causing periventricular leukomalacia, stroke in adults, and…

Pathophysiology of Subarachnoid Hemorrhage, Early Brain Injury, and Delayed Cerebral Ischemia

Introduction Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease that occurs after rupture of an intracranial aneurysm, promoting hemorrhage into the subarachnoid space. This leads to impairment of brain perfusion and function, contributing to brain injury after SAH. It has a complex, multisystem, and multifaceted pathogenesis. Intracranial aneurysms may be present in 2–3% of the population with an annual risk of rupture about 0.7–4% . Although…

Pathophysiology of Ischemia-Reperfusion Injury and Hemorrhagic Transformation in the Brain

Introduction Restoration of blood supply, referred to as “reperfusion,” is a desired goal for acute stroke treatment. Spontaneous reperfusion occurs commonly after stroke, in about 50–70% of patients with ischemic stroke. Reperfusion can also be achieved either by thrombolytic therapy using tissue plasminogen activator (tPA) or endovascular therapy, including embolectomy surgery using retrieval devices and thrombus disruption using stents. Since the publication of the first edition…

Histopathology of Intracerebral Hemorrhage

Introduction Intracerebral hemorrhage (ICH) is a subtype that is responsible for 10–15% of all strokes with significant morbidity and mortality. An ICH can be primary or secondary . A primary ICH results when a vulnerable small or large blood vessel ruptures without an identifiable reason for structural weakness and blood leaks out under pressure causing considerable damage to surrounding structures. A secondary ICH occurs when an…

Histopathology of Cerebral Ischemia and Stroke

Introduction The incidence of focal ischemia or stroke has been increasing over the last two decades with over 16 million new cases of stroke reported worldwide in 2010. Focal ischemic brain injury leads to local neurological deficits and a progression of histopathological changes depending on ischemic severity, location, and duration. In regions of developing infarction, acute neuronal alterations can progress through a series of phases including…

Thrombosis

Introduction Thrombosis resulting from various pathologies is the underlying cause of the majority of ischemic strokes. Hemostasis is the complex and highly regulated system that helps to maintain the integrity of blood and the vasculature. Maintenance of blood flow depends upon an intact and fully functional vascular endothelium. Thrombosis is one of the pathological consequences when the hemostatic system is activated within the circulation itself often…

An Overview of Atherosclerosis

Introduction Arteriosclerosis is a generic term used for describing hardening and thickening of arteries. Atherosclerosis is the most common form and is responsible for several common clinical manifestations such as stroke, coronary artery diseases, peripheral arterial disease, and aortic aneurysm. It is a major contributor to worldwide morbidity and mortality and in the Western world is responsible for more than half the annual mortality. It is…

Vascular Remodeling After Cerebral Ischemia

Acknowledgments This work was supported by NIH grant R01 NS071050 (JL), and VA merit award I01RX000655 (JL). Neovascularization After Cerebral Ischemia and Hypoxia Although the adult brain vascular network becomes quiescent after the completion of brain development, the remodeling of existing blood vessels or de novo vessel formation has been well documented after cerebral ischemia in both humans and laboratory animals as one of the CNS…

Gliogenesis

Introduction Brain pathophysiology is influenced by a dynamic balance between deleterious and beneficial responses to the initial insult . Stroke and brain injury trigger a wide spectrum of neurovascular perturbations, glial activation, and secondary neuroinflammation that may all amplify neuronal cell death cascades. But at the same time, many endogenous neuroprotective responses may also be activated (review by Moskowitz et al. ), and these beneficial processes include…

Neurogenesis in Cerebrovascular Disease

Introduction Tissue repair is as old as tissues themselves, as it can be observed in the most primitive multicellular organisms. However, evolution confers tissue complexity and cellular specialization at a price, which includes less effective repair capacity. As the most complex and most specialized tissue, brain is also the most difficult to regenerate after injury, such as that associated with cerebrovascular disease. Nevertheless, mechanisms for brain…

Eicosanoids in Cerebrovascular Diseases

Introduction Eicosanoids have long been known to participate in cerebrovascular injury, starting in the early 1970s . Eicosanoids are derivatives of the 20-carbon polyunsaturated fatty acid (PUFA) arachidonic acid (AA); the more generalized term for oxidized versions of PUFAs is oxylipins. Nonetheless, because of the physiological importance of AA-derived prostaglandins and leukotrienes, as well as the hydroxyeicosanoic acids (HETEs), eicosanoids is sometimes used as a blanket…

Cerebrovascular Activity of Peptides Generated by Central Nervous System

Introduction Peptides and Neuropeptides: Definitions Peptides are biologically occurring short chains of amino acid monomers linked by amide bonds. Arbitrarily, peptides are distinguished from proteins on the basis of size: they contain approximately 50 or fewer amino acids. Neuropeptides are peptides used by neurons to communicate with each other . Nerve cells communicate with each other through two mechanisms: (1) fast synaptic transmission through fast-acting neurotransmitter…

Adenosine and Its Receptors Update: Influence on Cerebral Blood Flow (CBF)

Introduction This chapter updates the data supporting the hypothesis that adenosine (Ado) is a metabolic regulator of cerebral blood flow (CBF). A metabolic regulator is a substance whose concentration reflects and is linked to cellular metabolism. If a factor is to be considered as a metabolic regulator of blood flow, it must fulfill certain criteria (see Table 14.1 ) . Table 14.1 Criteria for a Metabolic…

Perivascular Neurotransmitter Regulation of Cerebral Blood Flow

Introduction The brain circulation is generally believed to be controlled by (1) chemical factors as perivascular pH; (2) autoregulation, a response to changes in systemic blood pressure; and (3) intrinsic mechanisms within the brain via neurovascular units and the microvasculature. However, for decades it has been known that the major cerebral arteries and arterioles are supplied by perivascular nerves with origin in the sympathetic, parasympathetic, and…

CBF–Metabolism Coupling

Introduction The brain requires oxygen and glucose to meet its metabolic demands, and cerebral blood flow (CBF) is its supply channel. The brain has high energy requirements but limited storage capacity, which means persistent CBF is critical for its proper functioning and prevention of damage and death. Therefore, in spite of constituting only about 2% of total body weight, the brain is easily the most perfused…

Cerebral Blood Flow Regulation (Carbon Dioxide, Oxygen, and Nitric Oxide)

Introduction The effects of carbon dioxide (CO 2 ), oxygen (O 2 ), and nitric oxide (NO) on the cerebrovasculature are the most pronounced, easily demonstrated, and reproduced phenomena observed in the cerebral circulation. Studies in man and animals, using many different techniques, have shown that CO 2 , O 2 , and NO exert a profound influence on cerebral blood flow (CBF). Cerebral vasodilation to…

Cerebral Autoregulation

Introduction: From Static to Dynamic The human brain constitutes only 2% of the body weight, but receives 15% of cardiac output, accounts for almost 20% of the total oxygen consumption, and consumes approximately 25% of total body glucose utilization. The human brain is by far the most expensive organ in term of energy expenditure in the whole body. Maintenance and restoration of transmembrane resting potential dissipated…