Cerebrolysin restores balance between excitatory and inhibitory amino acids in brain following concussive head injury. Superior neuroprotective effects of TiO2 nanowired drug delivery

Hari Shanker Sharma*, Dafin F. Muresanu, Seaab Sahib, Z. Ryan Tian, José Vicente Lafuente, Anca D. Buzoianu, Rudy J. Castellani, Ala Nozari, Cong Li, Zhiquiang Zhang, Lars Wiklund, Aruna Sharma

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Concussive head injury (CHI) often associated with military personnel, soccer players and related sports personnel leads to serious clinical situation causing lifetime disabilities. About 3–4 k head injury per 100 k populations are recorded in the United States since 2000–2014. The annual incidence of concussion has now reached to 1.2% of population in recent years. Thus, CHI inflicts a huge financial burden on the society for rehabilitation. Thus, new efforts are needed to explore novel therapeutic strategies to treat CHI cases to enhance quality of life of the victims. CHI is well known to alter endogenous balance of excitatory and inhibitory amino acid neurotransmitters in the central nervous system (CNS) leading to brain pathology. Thus, a possibility exists that restoring the balance of amino acids in the CNS following CHI using therapeutic measures may benefit the victims in improving their quality of life. In this investigation, we used a multimodal drug Cerebrolysin (Ever NeuroPharma, Austria) that is a well-balanced composition of several neurotrophic factors and active peptide fragments in exploring its effects on CHI induced alterations in key excitatory (Glutamate, Aspartate) and inhibitory (GABA, Glycine) amino acids in the CNS in relation brain pathology in dose and time-dependent manner. CHI was produced in anesthetized rats by dropping a weight of 114.6 g over the right exposed parietal skull from a distance of 20 cm height (0.224 N impact) and blood–brain barrier (BBB), brain edema, neuronal injuries and behavioral dysfunctions were measured 8, 24, 48 and 72 h after injury. Cerebrolysin (CBL) was administered (2.5, 5 or 10 mL/kg, i.v.) after 4–72 h following injury. Our observations show that repeated CBL induced a dose-dependent neuroprotection in CHI (5–10 mL/kg) and also improved behavioral functions. Interestingly when CBL is delivered through TiO2 nanowires superior neuroprotective effects were observed in CHI even at a lower doses (2.5–5 mL/kg). These observations are the first to demonstrate that CBL is effectively capable to attenuate CHI induced brain pathology and behavioral disturbances in a dose dependent manner, not reported earlier.

Original languageEnglish (US)
Title of host publicationBrain Protection Strategies and Nanomedicine
EditorsHari Shanker Sharma, Aruna Sharma
PublisherElsevier B.V.
Pages211-267
Number of pages57
ISBN (Print)9780323989275
DOIs
StatePublished - Jan 2021
Externally publishedYes

Publication series

NameProgress in Brain Research
Volume266
ISSN (Print)0079-6123
ISSN (Electronic)1875-7855

Keywords

  • Aspartate
  • Blood–brain barrier
  • Brain edema
  • Cerebrolysin
  • Concussive head injury
  • GABA
  • Glutamate
  • Glycine
  • Head injury in military
  • Nanowired delivery
  • Neuronal injury
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

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