@inbook{37fceeaedf1c43c180ab4ba8a0bfc595,
title = "Concussive head injury exacerbates neuropathology of sleep deprivation: Superior neuroprotection by co-administration of TiO2-nanowired cerebrolysin, alpha-melanocyte-stimulating hormone, and mesenchymal stem cells",
abstract = "Sleep deprivation (SD) is common in military personnel engaged in combat operations leading to brain dysfunction. Military personnel during acute or chronic SD often prone to traumatic brain injury (TBI) indicating the possibility of further exacerbating brain pathology. Several lines of evidence suggest that in both TBI and SD alpha-melanocyte-stimulating hormone (α-MSH) and brain-derived neurotrophic factor (BDNF) levels decreases in plasma and brain. Thus, a possibility exists that exogenous supplement of α-MSH and/or BDNF induces neuroprotection in SD compounded with TBI. In addition, mesenchymal stem cells (MSCs) are very portent in inducing neuroprotection in TBI. We examined the effects of concussive head injury (CHI) in SD on brain pathology. Furthermore, possible neuroprotective effects of α-MSH, MSCs and neurotrophic factors treatment were explored in a rat model of SD and CHI. Rats subjected to 48 h SD with CHI exhibited higher leakage of BBB to Evans blue and radioiodine compared to identical SD or CHI alone. Brain pathology was also exacerbated in SD with CHI group as compared to SD or CHI alone together with a significant reduction in α-MSH and BDNF levels in plasma and brain and enhanced level of tumor necrosis factor-alpha (TNF-α). Exogenous administration of α-MSH (250 μg/kg) together with MSCs (1 × 106) and cerebrolysin (a balanced composition of several neurotrophic factors and active peptide fragments) (5 mL/kg) significantly induced neuroprotection in SD with CHI. Interestingly, TiO2 nanowired delivery of α-MSH (100 μg), MSCs, and cerebrolysin (2.5 mL/kg) induced enhanced neuroprotection with higher levels of α-MSH and BDNF and decreased the TNF-α in SD with CHI. These observations are the first to show that TiO2 nanowired administration of α-MSH, MSCs and cerebrolysin induces superior neuroprotection following SD in CHI, not reported earlier. The clinical significance of our findings in light of the current literature is discussed.",
keywords = "Blood-brain barrier, Cerebrolysin, Mesenchymal stem cells, Neuropathology, Sleep deprivation, Traumatic brain injury, α-MSH",
author = "Aruna Sharma and Muresanu, {Dafin F.} and Seaab Sahib and Tian, {Z. Ryan} and Castellani, {Rudy J.} and Ala Nozari and Lafuente, {Jos{\'e} Vicente} and Buzoianu, {Anca D.} and Igor Bryukhovetskiy and Igor Manzhulo and Ranjana Patnaik and Lars Wiklund and Sharma, {Hari Shanker}",
note = "Funding Information: This investigation is 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; Grants from the Alzheimer's Association (IIRG-09-132087), the National Institutes of Health (R01 AG028679) and the Dr. Robert M. Kohrman Memorial Fund (R.J.C.); Swedish Medical Research Council (Nr 2710-HSS), G{\"o}ran Gustafsson Foundation, Stockholm, Sweden (H.S.S.), Astra Zeneca, M{\"o}lndal, Sweden (H.S.S./A.S.), Alexander von Humboldt Foundation, Bonn, Germany (H.S.S.), The University Grants Commission, New Delhi, India (H.S.S./A.S.), Ministry of Science & Technology, Govt. of India (H.S.S./A.S.), Indian Medical Research Council, New Delhi, India (HSS/AS) and India-EU Co-operation Program (R.P./A.S./H.S.S.) and IT-901/16 (J.V.L.), Government of Basque Country and PPG 17/51 (J.V.L.), JVL thanks to the support of the University of the Basque Country (UPV/EHU) PPG 17/51 and 14/08, the Basque Government (IT-901/16 and CS-2203) Basque Country, Spain; and Foundation for Nanoneuroscience and Nanoneuroprotection (FSNN), Romania. Technical assistance of K{\"a}rstin Flink, Ingmarie Olsson, Uppsala University and Franzisca Drum, Katja Deparade, Free University Berlin, Germany are highly appreciated. Technical and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. Dr. Seaab Sahib is supported by Research Fellowship at University of Arkansas Fayetteville AR, USA by Department of Community Health; Middle Technical University; Wassit; Iraq, and The Higher Committee for Education Development in Iraq; Baghdad; Iraq. We thank Suraj Sharma, Blekinge Inst. Technology, Karlskrona, Sweden and Dr. Saja Alshafeay, Fayetteville, AR, USA affiliated with University of Baghdad, Baghdad IQ, for computer and graphic support. The U.S. Government is authorized to reproduce and distribute reprints for Government purpose notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the U.S. Government. Funding Information: This investigation is 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; Grants from the Alzheimer's Association (IIRG-09-132087), the National Institutes of Health (R01 AG028679) and the Dr. Robert M. Kohrman Memorial Fund (R.J.C.); Swedish Medical Research Council (Nr 2710-HSS), G?ran Gustafsson Foundation, Stockholm, Sweden (H.S.S.), Astra Zeneca, M?lndal, Sweden (H.S.S./A.S.), Alexander von Humboldt Foundation, Bonn, Germany (H.S.S.), The University Grants Commission, New Delhi, India (H.S.S./A.S.), Ministry of Science & Technology, Govt. of India (H.S.S./A.S.), Indian Medical Research Council, New Delhi, India (HSS/AS) and India-EU Co-operation Program (R.P./A.S./H.S.S.) and IT-901/16 (J.V.L.), Government of Basque Country and PPG 17/51 (J.V.L.), JVL thanks to the support of the University of the Basque Country (UPV/EHU) PPG 17/51 and 14/08, the Basque Government (IT-901/16 and CS-2203) Basque Country, Spain; and Foundation for Nanoneuroscience and Nanoneuroprotection (FSNN), Romania. Technical assistance of K?rstin Flink, Ingmarie Olsson, Uppsala University and Franzisca Drum, Katja Deparade, Free University Berlin, Germany are highly appreciated. Technical and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. Dr. Seaab Sahib is supported by Research Fellowship at University of Arkansas Fayetteville AR, USA by Department of Community Health; Middle Technical University; Wassit; Iraq, and The Higher Committee for Education Development in Iraq; Baghdad; Iraq. We thank Suraj Sharma, Blekinge Inst. Technology, Karlskrona, Sweden and Dr. Saja Alshafeay, Fayetteville, AR, USA affiliated with University of Baghdad, Baghdad IQ, for computer and graphic support. The U.S. Government is authorized to reproduce and distribute reprints for Government purpose notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the U.S. Government. The authors have no conflict of interests with any funding agency or entity reported here. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",
year = "2020",
month = jan,
doi = "10.1016/bs.pbr.2020.09.003",
language = "English (US)",
isbn = "9780128208137",
series = "Progress in Brain Research",
publisher = "Elsevier B.V.",
pages = "1--77",
editor = "Sharma, {Hari Shanker} and Aruna Sharma",
booktitle = "Neuropharmacology of Neuroprotection",
}