Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases

Peinado, M.A.; Ovelleiro, David; Moral, Marı́a Luisa Del; Hernández, Raquel; Martı́nez-Lara, Esther; Siles, Eva; Pedrajas, José Rafael; García-Martín, María Luisa; Caro, Carlos; Peralta, Sebastián; Morales, María Encarnación; Ruíz, M. A.; Blanco, Santos

doi:10.3390/ijms23010247

Cited by 4 publications

(9 citation statements)

References 86 publications

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“…Это может служить знаком того, что в 1-й подгруппе ССИГМ наблюдается активация компенсаторных механизмов нейронов. Они, вероятно, заключаются в увеличении активности аэробного гликолиза, что становится возможным благодаря доставке кислорода к митохондриям нейроглобином [17][18][19][20][21].…”

Section: Discussionunclassified

“…Повышенное содержание нейроглобина в цитоплазме нейронов в 1-й подгруппе ступенчатой субтотальной ишемии головного мозга с перевязкой обеих общих сонных артерий с интервалом 7 суток также может способствовать оптимизации поступления кислорода в митохондрии. Кроме того, нейроглобин является скэвенджером свободных радикалов, что способствует нормализации прооксидантно-антиоксидантного баланса головного мозга на свободнорадикальном этапе [20][21][22].…”

Section: Discussionunclassified

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The content of neuroglobin in neurons of the parietal cortex and hippocampus of rats with cerebral ischemia of varying severity

Bon,

Maksimovich,

Karnyushko

et al. 2023

Clin. Exp. Morphology

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Introduction. The role of neuroglobin ischemia is still unclear. Some studies indicate its neuroprotective effect due to increased expression of endothelial NOS. Other evidence refutes its significance for neuronal survival under oxygen-deficient conditions, as neuroglobin deficiency appears to increase HIF-1α expression. Materials and methods. The experiments were performed on 56 male outbred white rats weighing 258±18 g. Total cerebral ischemia was simulated by decapitation of animals, whereas the subtotal one was simulated by simultaneous ligation of both carotid arteries. Stepwise subtotal cerebral ischemia was performed by ligating both carotid arteries with an interval of 7 days (subgroup 1), 3 days (subgroup 2), or 1 day (subgroup 3). Results. The study found significant differences in neuroglobin content across three subgroups. In subgroup 1, there was a notable increase in neuroglobin content compared to the control group, with a 13% increase in the parietal cortex (p<0.05) and a 14% increase in the hippocampus (p<0.05). However, subgroup 2 showed a decrease in neuroglobin content, with a 13% decrease in the parietal cortex (p<0.05) and a 7% decrease in the hippocampus (p<0.05). The most significant decrease in neuroglobin content was observed in subgroup 3, with a 31% decrease (p<0.05) in the parietal cortex and a 33% decrease (p<0.05) in the hippocampus. In subgroup 3, the parietal cortex showed a 40% decrease in neuroglobin content compared to subgroup 1 (p<0.05) and a 21% decrease compared to subgroup 2 (p<0.05). Similarly, the hippocampus exhibited a 42.6% decrease in neuroglobin content compared to subgroup 1 (p<0.05) and a 28% decrease compared to subgroup 2 (p<0.05). Conclusion. Thus, the most pronounced disorders of the prooxidant-oxidant balance decreased neuroglobin were observed during a 1-day total cerebral ischemia. Keywords: neuroglobin, ischemia, pyramidal neurons, hippocampus, parietal cortex

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Section: Discussionunclassified

The content of neuroglobin in neurons of the parietal cortex and hippocampus of rats with cerebral ischemia of varying severity

Bon,

Maksimovich,

Karnyushko

et al. 2023

Clin. Exp. Morphology

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“…In this regard, we have carried out proteomic studies in an animal model of MCAO, detecting a total of 219 proteins that significantly changed their expression after stroke and treatment with nanoencapsulate-Ngb [55]. Interestingly, our analysis shows a strong upregulation of ATXN2L (Ataxin-2-like protein), a protein involved in the assembly of stress granules (formed in response to diverse cellular stresses) and processing bodies (responsible for cytoplasmic mRNA processing).…”

Section: Unraveling the Neuroprotective Action Mechanisms Of Ngbmentioning

confidence: 92%

“…The pharmaceutical preparation obtained (see later), was highly stable and biocompatible. In addition, it was able to transport the Ngb to the damaged neurons, thus demonstrating its neuroprotective effects against stroke [54][55][56].…”

Section: Current Treatments Against Strokementioning

confidence: 98%

New Strategies for Stroke Therapy: Nanoencapsulated Neuroglobin

et al. 2022

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Stroke is a global health and socio-economic problem. However, no efficient preventive and/or palliative treatments have yet been found. Neuroglobin (Ngb) is an endogen neuroprotective protein, but it only exerts its beneficial action against stroke after increasing its basal levels. Therefore, its systemic administration appears to be an efficient therapy applicable to stroke and other neurodegenerative pathologies. Unfortunately, Ngb cannot cross the blood-brain barrier (BBB), making its direct pharmacological use unfeasible. Thus, the association of Ngb with a drug delivery system (DDS), such as nanoparticles (NPs), appears to be a good strategy for overcoming this handicap. NPs are a type of DDS which efficiently transport Ngb and increase its bioavailability in the infarcted area. Hence, we previously built hyaluronate NPS linked to Ngb (Ngb-NPs) as a therapeutic tool against stroke. This nanoformulation induced an improvement of the cerebral infarct prognosis. However, this innovative therapy is still in development, and a more in-depth study focusing on its long-lasting neuroprotectant and neuroregenerative capabilities is needed. In short, this review aims to update the state-of-the-art of stroke therapies based on Ngb, paying special attention to the use of nanotechnological drug-delivering tools.

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“…Peinado et al [ 13 ] biosynthesized complex protein neuroglobin-hyaluronate nanoparticles (Ngb-NPs) to overcome the difficulty of experienced by Ngb in crossing the blood–brain barrier (BBB) and exerting neuroprotective effects at a brain level in an animal model of stroke (MCAO). They demonstrated that Ngb-NPs, when they are systemically, injected can cross the BBB and increase the survival of MCAO animals.…”

mentioning

confidence: 99%