Focused ultrasound and NXY-059 in experimental cerebral ischemia: A new therapeutic opportunity?
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CitationYuluğ, B., Hanoğlu, L., Yamaner, F. Y., Kılıç, E. ve Schabitz, W. R. (2016). Focused ultrasound and NXY-059 in experimental cerebral ischemia: A new therapeutic opportunity? CNS & Neurological Disorders-Drug Targets, 15(9), 1010-1013. https://dx.doi.org/10.2174/187152731509161007122800
troke is the third leading cause of morbidity and mortality worldwide. Many deleterious cellular pathways have been proposed to explain the molecular pathogenesis of this clinically devastating disease [1, 2]. The pathophysiology of stroke is complex and involves not only calcium and glutamate-mediated excitotoxicity but also various inflammatory pathways, disturbance of ionic balance, increased production of free radicals and neuronal cell apoptosis [3-5]. Besides its critical role for ion homeostasis in the central nervous system, disturbance of BBB integrity plays a significant role in stroke pathogenesis [6-8]. In this respect, recent studies have established that loss of BBB integrity and secondary loss of ion regulation may lead to brain edema and subsequent brain damage after cerebral ischemia [7, 9, 10]. This suggests that stabilization of the BBB could be brain protective, although recent studies failed to confirm this [11-13]. Moreover, data show that cerebral ischemia-induced BBB disruption is increased by 24 hours after middle cerebral artery occlusion , thus providing only a short window for transport of macromolecular drugs into the infarcted brain [14, 15]. This therapeutic time-frame effectively limits treatment efficacy due to an inability to achieve a sufficiently high dose of drug in the target brain area . Therapeutic agents are often difficult to administer to the brain due to BBB prevention of passage for systemically administered molecules and proteins [16-18]. Because of this pharmacological therapies have made limited progress, and much effort is now being directed to identify compounds that accumulate more efficaciously in the diseased brain.