Nanomaterials in Stroke Treatment

Abstract

Stroke is the world’s second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. About 87% of strokes are caused by ischemia, and the remainder is caused by hemorrhage. Ischemic stroke causes most deaths.1 Acute ischemic stroke results from a sudden decrease or loss of blood flow in cerebral arteries. Brain tissue has a relatively high consumption of oxygen and glucose, and depends almost exclusively on oxidative phosphorylation for energy production. Cerebral ischemia leads to the development of a cascade of pathological biochemical reactions, including the rapid depletion of the intracellular ATP pool, anaerobic glycolysis, lactate acidosis and membrane depolarization, glutamate excitotoxicity, the entry of Ca2+, Na+, and H2O into cells, activation of Ca-dependent proteins, mitochondrial dysfunction, overproduction of free radicals, activation of the immune system, gene overexpression, and, finally, cell death.1–3 Oxidative stress is one of the main mechanisms of stroke development. Free radical production and the activation of degradative enzymes lead to acute cell death through necrosis, but excitotoxic mechanisms can also initiate apoptosis.4 Besides causing cerebral cellular injury, oxidative stress also increases blood–brain barrier dysfunction.4,5 ### Stroke Treatment Major approaches developed to treat acute ischemic stroke fall into 2 categories, early recanalization (thrombolysis) and neuroprotection. There are ongoing trials aimed at evaluating the effectiveness of recombinant tissue–type plasminogen activator and acetylsalicylic acid in longer time windows with a finer selection of patients based on MRI and trials of novel recanalization methods.6 Neuroprotection is achieved by blocking of proinflammatory cytokines and cell adhesion agents, decrease of lipid peroxidation processes, and blocking of apoptosis.7 At least 25 clinical phase II and III trials are currently recruiting patients for the evaluation of new therapeutics for acute ischemic stroke.4 Despite these developments, the actual …