Abstract
Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies.
Highlights
Stroke has become a global social issue that threatens health, and shortens life expectancy, affecting the quality of life worldwide [1]
Cross the blood-brain barrier (BBB), and are Endocytosed by Neurons performed to ascertain the penetration of the Ngb attached to hyaluronate-NPs (Ngb-NPs) into the brain parenchyma, but Immunofluorescence techniques and further confocal microscopy observations were mainly to determine its cellular localization at the site of the lesion, the parietal cortex, in performed to ascertain the penetration of the Ngb-NPs into the brain parenchyma, but MCAO animals 24 h after the onset of reperfusion
Our research shows that as early as 24 h after stroke, the survival rates and the neurological scores improved with the Ngb-NPs treatment; on the other hand, no changes were detected in the infarct size, or in the oxidative and nitrosative stresses statuses
Summary
Stroke has become a global social issue that threatens health, and shortens life expectancy, affecting the quality of life worldwide [1]. The outcomes of imaging and pathological parameters are correlated to the results of learning and memory/mood studies [2] Both core and penumbra zones can be distinguished within the infarcted brain, the last one being susceptible to recuperation only in cases of mild infarct severity, and when specific treatments are available. When the insult is not treated immediately, the nervous cells of the infarcted area suffer severe damages due to oxygen and glucose deprivation, undergoing a number of changes, which include the inhibition of the electron transport chain, enhanced formation of reactive oxygen and nitrogen species, mitochondrial damage, energy depletion, and loss of ionic homeostasis, among others [6,7] These changes lead to cell swelling, membrane rupture, and eventually neuronal death, as usually occurs in the ischemic core [8]. 10−4 phosphoprotein phosphatase activity aminoacyl-tRNA ligase activity phosphatidylinositol-4,5-bisphosphate binding protein serine/threonine phosphatase activity amyloid-beta binding actin binding amide binding actin filament binding actin binding Endocytosis
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call