Sleep deprivation induced blood-brain barrier breakdown and brain pathology. Neuroprotective effects of TiO2-nanowired delivery of cerebrolysin and ondansetron

by Sharma, Aruna; Muresanu, Dafin F.; Lafuente, Jose Vicente; Ozkizilcik, Asya; Tian, Z. Ryan; Buzoianu, Anca D.; Sharma, Hari Shanker

Military personnel are often subjected to sleep deprivation (SD) for long hours during combat or peacekeeping operations across the Globe. Recent reports suggests that sound sleep for less than 4 h results in confusion, simple task calculations, and affects decision making. However, in military life SD of 12-72 h is quite common. It appears that longer duration of SD is related to brain dysfunction. Model experiments carried out in our laboratory show that 12-72 h of SD in rats results in progressive breakdown of the blood-brain barrier (BBB) to proteins and induce brain edema formation. Selective neuronal, glial cell and axonal injuries also occurred in SD that is progressive in nature. Interestingly, the magnitude and intensity of SD depends on environmental temperature and cardiovascular health of the animals. Thus, SD at 34 C induces 2- to 4- fold brain damage, BBB breakdown and edema formation in rats as compared to identical SD at room temperature (21 1 C). Also hypertensive rats when subjected to identical SD showed greater degree of brain pathology as compared to normotensive animals. Treatment with a multimodal drug Cerebrolysin that is a balanced composition of several neurotrophic factors and active peptide fragments significantly reduced the brain pathology in healthy animals at room temperature. However, TiO2-nanowired delivery of cerebrolysin is needed to attenuate SD induced brain pathology of normotensive rats at hot environment or hypertensive animals at room temperature. These observations suggest that nanodrug delivery in SD is needed to induce neuroprotection at hot environment or in hypertensive animals, not reported earlier. Springer International Publishing AG 2017.

Drug and Gene Delivery to the Central Nervous System for Neuroprotection: Nanotechnological Advances
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