@inbook{c30b5c9ce27c42fe9a4f22c196d979df,
title = "Topical application of CNTF, GDNF and BDNF in combination attenuates blood-spinal cord barrier permeability, edema formation, hemeoxygenase-2 upregulation, and cord pathology",
abstract = "Spinal cord injury (SCI) is one of the leading causes of disability in Military personnel for which no suitable therapeutic strategies are available till today. Thus, exploration of novel therapeutic measures is highly needed to enhance the quality of life of SCI victims. Previously, topical application of BDNF and GDNF in combination over the injured spinal cord after 90 min induced marked neuroprotection. In present investigation, we added CNTF in combination with BDNF and/or GDNF treatment to examine weather the triple combination applied over the traumatic cord after 90 or 120 min could thwart cord pathology. Since neurotrophins attenuate nitric oxide (NO) production in SCI, the role of carbon monoxide (CO) production that is similar to NO in inducing cell injury was explored using immunohistochemistry of the constitutive isoform of enzyme hemeoxygenase-2 (HO-2). SCI inflicted over the right dorsal horn of the T10–11 segments by making an incision of 2 mm deep and 5 mm long upregulated the HO-2 immunostaining in the T9 and T12 segments after 5 h injury. These perifocal segments are associated with breakdown of the blood-spinal cord barrier (BSCB), edema development and cell injuries. Topical application of CNTF with BDNF and GDNF in combination (10 ng each) after 90 and 120 min over the injured spinal cord significantly attenuated the BSCB breakdown, edema formation, cell injury and overexpression of HO-2. These observations are the first to show that CNTF with BDNF and GDNF induced superior neuroprotection in SCI probably by downregulation of CO production, not reported earlier.",
keywords = "BDNF, Blood-spinal cord barrier, CNTF, GDNF, Hemeoxygenase 2, Spinal cord edema, Spinal cord injury",
author = "Aruna Sharma and Lianyuan Feng and Muresanu, {Dafin F.} and Hongyun Huang and Menon, {Preeti K.} and Seaab Sahib and {Ryan Tian}, Z. and Lafuente, {Jos{\'e} Vicente} and Buzoianu, {Anca D.} and Castellani, {Rudy J.} and Ala Nozari 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; Ministry of Science & Technology, People Republic of China, the Alzheimer's Association (IIRG-09-132087), the National Institutes of Health (R01 AG028679) and the Dr. Robert M. Kohrman Memorial Fund (RJC); Swedish Medical Research Council (Nr 2710-HSS), G{\"o}ran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, M{\"o}lndal, Sweden (HSS/AS), The University Grants Commission , New Delhi, India (HSS/AS), Ministry of Science & Technology, Govt. of India (HSS/AS), Indian Medical Research Council , New Delhi, India (HSS/AS) and India-EU Co-operation Program (RP/AS/HSS) and IT-901/16 (JVL), Government of Basque Country and PPG 17/51 (JVL), 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 and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. Dr. Seaab Sahib is supported by Research Fellowship at the University of Arkansas , Fayetteville, AR, 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, University of Arkansas Fayetteville, AR, USA, 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; Ministry of Science & Technology, People Republic of China, the Alzheimer's Association (IIRG-09-132087), the National Institutes of Health (R01 AG028679) and the Dr. Robert M. Kohrman Memorial Fund (RJC); Swedish Medical Research Council (Nr 2710-HSS), G?ran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, M?lndal, Sweden (HSS/AS), The University Grants Commission, New Delhi, India (HSS/AS), Ministry of Science & Technology, Govt. of India (HSS/AS), Indian Medical Research Council, New Delhi, India (HSS/AS) and India-EU Co-operation Program (RP/AS/HSS) and IT-901/16 (JVL), Government of Basque Country and PPG 17/51 (JVL), 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 and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. Dr. Seaab Sahib is supported by Research Fellowship at the University of Arkansas, Fayetteville, AR, 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, University of Arkansas Fayetteville, AR, USA, 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. There is no conflict of interest between any entity and organization mentioned here. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",
year = "2021",
month = jan,
doi = "10.1016/bs.pbr.2021.06.013",
language = "English (US)",
isbn = "9780323989275",
series = "Progress in Brain Research",
publisher = "Elsevier B.V.",
pages = "357--376",
editor = "Sharma, {Hari Shanker} and Aruna Sharma",
booktitle = "Brain Protection Strategies and Nanomedicine",
}