Neuropathology and Pathophysiology of Stroke

The vascular origin of cerebrovascular disease All cerebrovascular diseases (CVD) have their origin in the vessels supplying or draining the brain. Therefore, knowledge of pathological changes occurring in the vessels and in the blood is essential for understanding the pathophysiology of the various types of CVD and for the planning of efficient therapeutic strategies. Changes in the vessel wall lead to obstruction of blood flow, by interacting with blood constituents they may cause thrombosis and blockade of blood flow in this vessel. In addition to vascular stenosis or occlusion at the site of vascular changes, disruption of blood supply and consecutive infarcts can also be produced by emboli arising from vascular lesions situated proximally to otherwise healthy branches located more distal in the arterial tree or from a source located in the heart. At the site of occlusion, the opportunity exists for thrombus to develop in anterograde fashion throughout the length of the vessel, but this event seems to occur only rarely. Changes in large arteries supplying the brain, including the aorta, are mainly caused by atherosclerosis. Middle-sized and intracerebral arteries can also be affected by acute or chronic vascular diseases of inflammatory origin due to subacute to chronic infections, e.g. tuberculosis and lues, or due to collagen disorders, e.g. giant cell arteriitis, granulomatous angiitis of the CNS, panarteritis nodosa, and even more rarely systemic lupus erythematosus, Takayasu’s arteriitis, Wegener granulomatosis, rheumatoid arteriitis, Sjogren’s syndrome, or Sneddon and Behcet’s disease. In some diseases affecting the vessels of the brain the etiology and pathogenesis are still unclear, e.g. moyamoya disease and fibromuscular dysplasia, but these disorders are characterized by typical locations of the vascular changes. Some arteriopathies are hereditary, such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), and in some such as cerebral amyloid angiopathy a degenerative cause has been suggested. All these vascular disorders can cause obstruction, and lead to thrombosis and embolizations. Small vessels of the brain are affected by hyalinosis and fibrosis; this “small-vessel disease” can cause lacunes and, if widespread, is the substrate for vascular cognitive impairment and vascular dementia. Atherosclerosis is the most widespread disorder leading to death and serious morbidity including stroke. The basic pathological lesion is the atheromatous plaque, and the most commonly affected sites are the aorta, the coronary arteries, the carotid artery at its bifurcation, and the basilar artery. Arteriosclerosis, a more generic term describing hardening and thickening of the arteries, includes as an additional type Monkeberg’s sclerosis and is characterized by calcification in the tunica media and arteriolosclerosis with proliferative and hyaline changes affecting the arterioles. Atherosclerosis starts at a young age, and lesions accumulate and grow throughout life and become symptomatic and clinically evident when end organs are affected [1].