Diabetes exacerbates brain pathology following a focal blast brain injury: New role of a multimodal drug cerebrolysin and nanomedicine

Dafin F. Muresanu, Aruna Sharma*, Seaab Sahib, Z. Ryan Tian, Lianyuan Feng, Rudy J. Castellani, Ala Nozari, José Vicente Lafuente, Anca D. Buzoianu, Per Ove Sjöquist, Ranjana Patnaik, Lars Wiklund, Hari Shanker Sharma

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

Abstract

Blast brain injury (bBI) is a combination of several forces of pressure, rotation, penetration of sharp objects and chemical exposure causing laceration, perforation and tissue losses in the brain. The bBI is quite prevalent in military personnel during combat operations. However, no suitable therapeutic strategies are available so far to minimize bBI pathology. Combat stress induces profound cardiovascular and endocrine dysfunction leading to psychosomatic disorders including diabetes mellitus (DM). This is still unclear whether brain pathology in bBI could exacerbate in DM. In present review influence of DM on pathophysiology of bBI is discussed based on our own investigations. In addition, treatment with cerebrolysin (a multimodal drug comprising neurotrophic factors and active peptide fragments) or H-290/51 (a chain-breaking antioxidant) using nanowired delivery of for superior neuroprotection on brain pathology in bBI in DM is explored. Our observations are the first to show that pathophysiology of bBI is exacerbated in DM and TiO2-nanowired delivery of cerebrolysin induces profound neuroprotection in bBI in DM, not reported earlier. The clinical significance of our findings with regard to military medicine is discussed.

Original languageEnglish (US)
Title of host publicationNeuropharmacology of Neuroprotection
EditorsHari Shanker Sharma, Aruna Sharma
PublisherElsevier B.V.
Pages285-367
Number of pages83
ISBN (Print)9780128208137
DOIs
StatePublished - Jan 2020

Publication series

NameProgress in Brain Research
Volume258
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855

Funding

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-H.S.S.), Göran Gustafsson Foundation, Stockholm, Sweden (H.S.S.), Astra Zeneca, Mölndal, 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 (H.S.S./A.S.) 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.), J.V.L. 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 Kärstin 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. 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-H.S.S.), Göran Gustafsson Foundation, Stockholm, Sweden (H.S.S.), Astra Zeneca, Mölndal, 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 (H.S.S./A.S.) 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.), J.V.L. 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 Kärstin 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.

Keywords

  • Blast brain injury
  • Brain pathology
  • Cerebrolysin
  • Diabetes mellitus
  • H-290/51 Nanomedicine
  • Neuroprotection

ASJC Scopus subject areas

  • General Neuroscience

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