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

Research output: Chapter in Book/Report/Conference proceedingChapter

1 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 languageEnglish (US)
Title of host publicationNanomedicine and Neuroprotection in Brain Diseases
EditorsHari Shanker Sharma, Aruna Sharma
PublisherElsevier B.V.
Pages139-230
Number of pages92
ISBN (Print)9780323901628
DOIs
StatePublished - Jan 2021

Publication series

NameProgress in Brain Research
Volume265
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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