Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury

Feng Niu; Aruna Sharma; Zhenguo Wang; Lianyuan Feng; Dafin F. Muresanu; Seaab Sahib; Z. Ryan Tian; José Vicente Lafuente; Anca D. Buzoianu; Rudy J. Castellani; Ala Nozari; Preeti K. Menon; Ranjana Patnaik; Lars Wiklund; Hari Shanker Sharma

doi:10.1016/bs.pbr.2021.06.004

Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury

Feng Niu, Aruna Sharma^*, Zhenguo Wang, Lianyuan Feng, Dafin F. Muresanu, Seaab Sahib, Z. Ryan Tian, José Vicente Lafuente, Anca D. Buzoianu, Rudy J. Castellani, Ala Nozari, Preeti K. Menon, Ranjana Patnaik, Lars Wiklund, Hari Shanker Sharma

^*Corresponding author for this work

Pathology

Research output: Chapter in Book/Report/Conference proceeding › Chapter

8 Scopus citations

Abstract

Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.

Original language	English (US)
Title of host publication	Nanomedicine and Neuroprotection in Brain Diseases
Editors	Hari Shanker Sharma, Aruna Sharma
Publisher	Elsevier B.V.
Pages	139-230
Number of pages	92
ISBN (Print)	9780323901628
DOIs	https://doi.org/10.1016/bs.pbr.2021.06.004
State	Published - Jan 2021

Publication series

Name	Progress in Brain Research
Volume	265
ISSN (Print)	0079-6123
ISSN (Electronic)	1875-7855

Funding

This investigation is supported by grants from the Ministry of Science & Technology, People Republic of China, 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 (RJC); Swedish Medical Research Council (Nr 2710-HSS), 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, 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, 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.

Keywords

Blood-brain barrier
Brain edema
Brain pathology
Concussive head injury
Functional deficit
Neuroprotection
Oxiracetam
TiO2 nanowired delivery

ASJC Scopus subject areas

General Neuroscience

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Cite this

Niu, F., Sharma, A., Wang, Z., Feng, L., Muresanu, D. F., Sahib, S., Tian, Z. R., Lafuente, J. V., Buzoianu, A. D., Castellani, R. J., Nozari, A., Menon, P. K., Patnaik, R., Wiklund, L., & Sharma, H. S. (2021). Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury. In H. S. Sharma, & A. Sharma (Eds.), Nanomedicine and Neuroprotection in Brain Diseases (pp. 139-230). (Progress in Brain Research; Vol. 265). Elsevier B.V.. https://doi.org/10.1016/bs.pbr.2021.06.004

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title = "Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury",

abstract = "Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.",

keywords = "Blood-brain barrier, Brain edema, Brain pathology, Concussive head injury, Functional deficit, Neuroprotection, Oxiracetam, TiO2 nanowired delivery",

author = "Feng Niu and Aruna Sharma and Zhenguo Wang and Lianyuan Feng and Muresanu, {Dafin F.} and Seaab Sahib and Tian, {Z. Ryan} and Lafuente, {Jos{\'e} Vicente} and Buzoianu, {Anca D.} and Castellani, {Rudy J.} and Ala Nozari and Menon, {Preeti K.} and Ranjana Patnaik and Lars Wiklund and Sharma, {Hari Shanker}",

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year = "2021",

month = jan,

doi = "10.1016/bs.pbr.2021.06.004",

language = "English (US)",

isbn = "9780323901628",

series = "Progress in Brain Research",

publisher = "Elsevier B.V.",

pages = "139--230",

editor = "Sharma, {Hari Shanker} and Aruna Sharma",

booktitle = "Nanomedicine and Neuroprotection in Brain Diseases",

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Niu, F, Sharma, A, Wang, Z, Feng, L, Muresanu, DF, Sahib, S, Tian, ZR, Lafuente, JV, Buzoianu, AD, Castellani, RJ, Nozari, A, Menon, PK, Patnaik, R, Wiklund, L & Sharma, HS 2021, Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury. in HS Sharma & A Sharma (eds), Nanomedicine and Neuroprotection in Brain Diseases. Progress in Brain Research, vol. 265, Elsevier B.V., pp. 139-230. https://doi.org/10.1016/bs.pbr.2021.06.004

Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury. / Niu, Feng; Sharma, Aruna; Wang, Zhenguo et al.
Nanomedicine and Neuroprotection in Brain Diseases. ed. / Hari Shanker Sharma; Aruna Sharma. Elsevier B.V., 2021. p. 139-230 (Progress in Brain Research; Vol. 265).

Research output: Chapter in Book/Report/Conference proceeding › Chapter

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AU - Wang, Zhenguo

AU - Feng, Lianyuan

AU - Muresanu, Dafin F.

AU - Sahib, Seaab

AU - Tian, Z. Ryan

AU - Lafuente, José Vicente

AU - Buzoianu, Anca D.

AU - Castellani, Rudy J.

AU - Nozari, Ala

AU - Menon, Preeti K.

AU - Patnaik, Ranjana

AU - Wiklund, Lars

AU - Sharma, Hari Shanker

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N2 - Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.

AB - Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.

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KW - Brain pathology

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Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury

Abstract

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Keywords

ASJC Scopus subject areas

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