Sharma Hari Shanker, Muresanu Dafin F, Nozari Ala, Lafuente José Vicente, Buzoianu Anca D, Tian Z Ryan, Huang Hongyun, Feng Lianyuan, Bryukhovetskiy Igor, Manzhulo Igor, Wiklund Lars, Sharma Aruna
International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
Department of Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca, Romania.
Adv Neurobiol. 2023;32:139-192. doi: 10.1007/978-3-031-32997-5_4.
Concussive head injury (CHI) is one of the major risk factors in developing Alzheimer's disease (AD) in military personnel at later stages of life. Breakdown of the blood-brain barrier (BBB) in CHI leads to extravasation of plasma amyloid beta protein (ΑβP) into the brain fluid compartments precipitating AD brain pathology. Oxidative stress in CHI or AD is likely to enhance production of nitric oxide indicating a role of its synthesizing enzyme neuronal nitric oxide synthase (NOS) in brain pathology. Thus, exploration of the novel roles of nanomedicine in AD or CHI reducing NOS upregulation for neuroprotection are emerging. Recent research shows that stem cells and neurotrophic factors play key roles in CHI-induced aggravation of AD brain pathologies. Previous studies in our laboratory demonstrated that CHI exacerbates AD brain pathology in model experiments. Accordingly, it is quite likely that nanodelivery of NOS antibodies together with cerebrolysin and mesenchymal stem cells (MSCs) will induce superior neuroprotection in AD associated with CHI. In this review, co-administration of TiO nanowired cerebrolysin - a balanced composition of several neurotrophic factors and active peptide fragments, together with MSCs and monoclonal antibodies (mAb) to neuronal NOS is investigated for superior neuroprotection following exacerbation of brain pathology in AD exacerbated by CHI based on our own investigations. Our observations show that nanowired delivery of cerebrolysin, MSCs and neuronal NOS in combination induces superior neuroprotective in brain pathology in AD exacerbated by CHI, not reported earlier.
脑震荡性头部损伤（CHI）是军事人员在生命后期患阿尔茨海默病（AD）的主要危险因素之一。CHI中血脑屏障（BBB）的破坏导致血浆淀粉样β蛋白（ΑβP）渗入脑脊液腔，从而引发AD脑病理改变。CHI或AD中的氧化应激可能会增强一氧化氮的产生，表明其合成酶神经元型一氧化氮合酶（NOS）在脑病理中发挥作用。因此，探索纳米医学在AD或CHI中减少NOS上调以实现神经保护的新作用正在兴起。最近的研究表明，干细胞和神经营养因子在CHI诱导的AD脑病理加重中起关键作用。我们实验室之前的研究表明，在模型实验中CHI会加剧AD脑病理。因此，将NOS抗体与脑蛋白水解物和间充质干细胞（MSCs）进行纳米递送很可能会在与CHI相关的AD中诱导出更好的神经保护作用。在这篇综述中，基于我们自己的研究，研究了TiO纳米线脑蛋白水解物（几种神经营养因子和活性肽片段的平衡组合物）与MSCs和神经元型NOS单克隆抗体（mAb）联合给药，以在CHI加重的AD脑病理加重后实现更好的神经保护。我们的观察结果表明，纳米线递送脑蛋白水解物、MSCs和神经元型NOS的组合在CHI加重的AD脑病理中诱导出更好的神经保护作用，这在之前没有报道过。
