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Sleep Deprivation Induced Blood-Brain Barrier Breakdown and Brain Pathology. Neuroprotective Effects of TiO2-Nanowired Delivery of Cerebrolysin and Ondansetron

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Drug and Gene Delivery to the Central Nervous System for Neuroprotection

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Abstract

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.

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Acknowledgements

Part of this research on Ondansetron in Sleep Deprivation as Innovation was accepted in the National Innovation Summit & Showcase, TechConnect 2014, National Harbor, Washington DC, USA Jun 15-18, 2014. This investigation was supported by grants from the Air Force Office of Scientific Research (EOARD, London, UK), and Air Force Material Command, USAF, under grant number FA8655-05-1-3065; Swedish Medical Research Council (Nr 2710-HSS), Swedish Strategic Research Foundation, Stockholm, Sweden; Göran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, Mölndal, Sweden (HSS/AS), The University Grants Commission, New Delhi, India (HSS/AS), Ministry of Science & Technology, governments of India and Sweden (HSS/AS), Indian Medical Research Council, New Delhi, India (HSS/AS); India-EU Research Co-operation Program (RP/AS/HSS) and IT 901/16 (JVL), Government of Basque Country and UFI 11/32 (JVL); University of Basque Country, Spain.

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Authors and Affiliations

  1. International Experimental Central Nervous System Injury & Repair (IECNSIR), Laboratory of Cerebrovascular Biology, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, Frödingsgatan 12, Bldg. 28, LGH 1103, 75421, Uppsala, Sweden

    Aruna Sharma & Hari S. Sharma Ph.D., Dr Med Sci

  2. Department of Neurosciences, University of Basque Country, Bilbao, Spain

    Aruna Sharma, José Vicente Lafuente & Hari S. Sharma Ph.D., Dr Med Sci

  3. Department Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca, Romania

    Dafin F. Muresanu

  4. “RoNeuro” Institute for Neurological Research and Diagnostic, 37 Mircea Eliade Street, 400364, Cluj-Napoca, Romania

    Dafin F. Muresanu

  5. Department Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA

    Asya Ozkizilcik

  6. Department of Chemistry & Biochemistry, University of Arkansas, Fayetteville, AR, USA

    Z. Ryan Tian

  7. Department of Pharmacology, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Anca D. Buzoianu

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  1. Aruna Sharma
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  6. Anca D. Buzoianu
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  7. Hari S. Sharma Ph.D., Dr Med Sci
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Corresponding author

Correspondence to Hari S. Sharma Ph.D., Dr Med Sci .

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Editors and Affiliations

  1. International Experimental Central Nervous System Injury & Repair (IECNSIR), Laboratory of Cerebrovascular Biology, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden

    Hari S. Sharma

  2. Department of Clinical Neurosciences, University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Dafin F. Muresanu

  3. International Experimental Central Nervous System Injury & Repair (IECNSIR), Laboratory of Cerebrovascular Biology, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden

    Aruna Sharma

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Sharma, A. et al. (2017). Sleep Deprivation Induced Blood-Brain Barrier Breakdown and Brain Pathology. Neuroprotective Effects of TiO2-Nanowired Delivery of Cerebrolysin and Ondansetron. In: Sharma, H., Muresanu, D., Sharma, A. (eds) Drug and Gene Delivery to the Central Nervous System for Neuroprotection. Springer, Cham. https://doi.org/10.1007/978-3-319-57696-1_5

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