Pathophysiology and therapeutic targets for ischemic stroke

Abstract

Summary:The increased risk for stroke among those who have had a previous stroke or transient ischemic attack (TIA) and the tremendous burden of disability among stroke sufferers make both primary and secondary preventative strategies imperative. An understanding of the pathophysiology of stroke and TIA can help identify appropriate therapeutic targets. Stroke and Heart Disease Shared Pathology and Risk FactorsUnderlying atherosclerosis, which plays a significant role in both ischemic stroke and myocardial infarction (MI), is similar in both conditions. Despite this similarity, however, these two disease states are characterized by distinct differences in pathophysiology that go beyond the mere location of the thrombus. Coronary artery lesions tend to be more fibrotic than those found in the cerebral vasculature. 1, 2 Stroke patients are an extremely heterogeneous group compared with those who have had an MI. There is a variety of sources for the thrombus as well as numerous areas in which ischemic occlusion can occur. The evolution of the consequences of the ischemic event also differs in stroke and MI. Stroke pathology pursues a much longer course than MI, with secondary damage and metabolic sequelae occurring at times up to a month after the initial event. 3 The neurological complications and clinical manifestations following a stroke vary considerably as well, depending upon which areas of the brain were affected and to what degree. Patients may suffer from any combination of cognitive, motor, visual, sensory, language, speech, or mood deficits. Deficits can be discrete or global. Finally, despite the pervasive notion that stroke patients are at increased risk for acute MI, in up to 75% of stroke survivors a subsequent cardiovascular event could be another stroke. 4 However, both stroke and MI share many risk factors. Hypertension and diabetes mellitus are important modifiable risk factors for both stroke and heart failure. 5 In fact, cardiovascular disease, including stroke and heart disease, is the primary cause of death in persons with diabetes. 6 Hyperlipidemia is an accepted risk factor for coronary artery disease, and its contribution to ischemic stroke is also important. 7-10 Data from studies indicate that use of the beta-hydroxy-betamethylglutaryl-CoA reductase inhibitors or statins (cholesterol-lowering drugs) offers stroke protection and reduces the amount of carotid atheroma, although the mechanisms involved are unclear. [7][8][9][10] Lifestyle factors, such as obesity and smoking, and use of a number of chemical substances, including alcohol and both legal and illegal drugs, have been associated with cardiovascular disease in general and stroke in particular. 7,11,12 Some prescription medications have been associated with an increased incidence of stroke. In the past, early-generation oral contraceptives were found to increase stroke risk, 13 and controversy has surrounded hormone replacement therapy (HRT), with recent findings from the Hormone and Estrogen/progestin Replacement Study (HERS) a...

Green Tea with Its Active Compound EGCG for Acute Ischemic Stroke Treatment

“…CSD occurs when the extracellular K+ level exceeds a critical threshold [43]. This CSD wave in ischemic conditions will reach the peri-ischemic area and expand the infarct area (Figure 1) [6,46,47].…”

“…These radicals can be neutralized or even attack other biomolecules in the cell. Hydroxyl radicals cause Ischemic cascade in stroke [47].…”

Immunity in Stroke: The Next Frontier

“…After the onset of ischemic stroke, the lack of oxygen and energy failure in the ischemic tissue triggers a series of deleterious cellular and molecular events. 9 In the acute phase, blood platelets adhere and become activated at the site of ischemic vascular injury. Activated platelets interact with T cells and neutrophils to promote thrombus formation and trigger thromboinflammation through the activation of the kallikrein–kinin system.…”

Green tea and its active compound epigallocathechin-3-gallate (EGCG) inhibit neuronal apoptosis in a middle cerebral artery occlusion (MCAO) model

“…There is a decrease in blood flow during ischemic stroke that causes a decrease in adenosine triphosphate (ATP) production and causes lactic acidosis and homeostatic ion imbalance [1][2][3]. Homeostatic ion imbalance will cause calcium influx that will trigger phospholipase and protease and will damage cell membrane and protein [4,5]. An increase in intracellular calcium will also trigger reactive oxygen species on mitochondria that will cause damage [6,7].…”