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Parkinson disease and intranasal

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https://www.readbyqxmd.com/read/29164519/atorvastatin-prevents-early-oxidative-events-and-modulates-inflammatory-mediators-in-the-striatum-following-intranasal-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-administration-in-rats
#1
Naiani F Marques, Adalberto A Castro, Gianni Mancini, Fernanda L Rocha, Adair R S Santos, Rui D Prediger, Andreza Fabro De Bem, Carla I Tasca
Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor with cholesterol-lowering, anti-inflammatory, and antioxidant properties. Increasing evidence show atorvastatin acts as a protective agent against insults in the central nervous system (CNS). The regular use of statins has been associated with a reduced risk of Parkinson's disease (PD) development. Here, we evaluated early events involved in the neurotoxicity induced by intranasal (i.n.) infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats and the potential of atorvastatin to prevent these early toxic events...
November 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29132545/nanoformulation-a-useful-therapeutic-strategy-for-improving-neuroprotection-and-the-neurorestorative-potential-in-experimental-models-of-parkinson-s-disease
#2
Jose V Lafuente, Catalina Requejo, Alejandro Carrasco, Harkaitz Bengoetxea
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. Experimental models are necessary to go deeper in the comprehension of pathophysiological mechanism and to assess new therapeutic strategies. The unilateral 6-hydroxydopamine (6-OHDA) lesion either in medial forebrain bundle (MFB) or into the striatum in rats affords to study various stages of PD depending on the evolution time lapsed. A promising alternative to address the neurodegenerative process is the use of neurotrophic factors; but its clinical use has been limited due to its short half-life and rapid degradation after in vivo administration, along with difficulties for crossing the blood-brain barrier (BBB)...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29101619/impairment-of-non-associative-learning-in-a-rat-experimental-model-of-preclinical-stage-of-parkinson-s-disease
#3
I N Abdurasulova, I V Ekimova, A V Matsulevich, A R Gazizova, V M Klimenko, Yu F Pastukhov
An experimental model of the preclinical stage of Parkinson's disease was induced by double intranasal administration of the proteasome inhibitor lactacystin. The results demonstrated signs of cognitive impairments expressed as impaired non-associative learning. This was related to degeneration of one-third of dopaminergic neurons in the ventral tegmental area of the midbrain and their axons in the dorsolateral prefrontal cortex. Impairment of non-associative learning may be an early non-motor marker of Parkinson's disease indicating the start of neurodegenerative processes in the dopaminergic mesocortical system of the brain...
September 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28870559/intranasal-deferoxamine-affects-memory-loss-oxidation-and-the-insulin-pathway-in-the-streptozotocin-rat-model-of-alzheimer-s-disease
#4
J M Fine, A C Forsberg, B M Stroebel, K A Faltesek, D R Verden, K A Hamel, E B Raney, J M Crow, L R Haase, K E Knutzen, K D Kaczmarczek, W H Frey, L R Hanson
Accumulation of metal and the accompanying increase in oxidative stress and inflammation plays an important role in neurodegenerative disease. Deferoxamine (DFO) is a metal chelator found to be beneficial in several animal models of neurodegenerative disease and insult including Alzheimer's disease, Parkinson's disease, stroke, and subarachnoid hemorrhage. In this study, we determine whether intranasally (IN) administered DFO is beneficial in the intracerebroventricular streptozotocin (ICV STZ) rat model of sporadic Alzheimer's disease, which is different from previous models in that it exhibits dysregulation of insulin metabolism as well as oxidative stress and inflammation...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28866799/intranasal-administration-of-tat-conjugated-lipid-nanocarriers-loading-gdnf-for-parkinson-s-disease
#5
Sara Hernando, Enara Herran, Joana Figueiro-Silva, José Luis Pedraz, Manoli Igartua, Eva Carro, Rosa Maria Hernandez
Parkinson's disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years, growth factors (GFs) have been raised as a promising therapeutic approach to address the underlying neurodegenerative process. Among others, glial cell-derived neurotrophic factor (GDNF) is a widely studied GF for PD...
September 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28728000/tailor-made-purified-human-platelet-lysate-concentrated-in-neurotrophins-for-treatment-of-parkinson-s-disease
#6
Ming-Li Chou, Joe-Wei Wu, Flore Gouel, Aurélie Jonneaux, Kelly Timmerman, Ting-Yi Renn, Charlotte Laloux, Hung-Ming Chang, Liang-Tzung Lin, Jean-Christophe Devedjian, David Devos, Thierry Burnouf
Human platelet lysates (PLs), which contain multiple neurotrophins, have been proposed for treating neurodegenerative disorders, including Parkinson's disease (PD). However, current PLs suspended in plasma have high protein content and contain fibrinogen/fibrin and, following activation, also proteolytic and thrombogenic enzymes. Upon brain administration, such PLs may saturate the cerebrospinal fluid and exert neurotoxicity. We assessed whether purified PLs, concentrated in neurotrophins, protected dopaminergic neurons in PD models...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28627590/activation-of-sonic-hedgehog-signal-by-purmorphamine-in-a-mouse-model-of-parkinson-s-disease-protects-dopaminergic-neurons-and-attenuates-inflammatory-response-by-mediating-pi3k-akt-signaling-pathway
#7
Shuai Shao, Guang-Liang Wang, Cespuglio Raymond, Xue-Hua Deng, Xiao-Lan Zhu, Di Wang, Le-Peng Hong
In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti‑inflammatory and neuroprotective effects of this signaling pathway remain poorly understood...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28610743/valproate-and-sodium-butyrate-attenuate-manganese-decreased-locomotor-activity-and-astrocytic-glutamate-transporters-expression-in-mice
#8
James Johnson, Edward Alain B Pajarillo, Equar Taka, Romonia Reams, Deok-Soo Son, Michael Aschner, Eunsook Lee
Manganese (Mn) is an essential trace element, but chronic overexposure to this metal, either environmentally or occupationally may cause manganism, a disease analogous to Parkinson's disease. Inhibitors of histone deacetylases, such as valproic acid (VPA) and sodium butyrate (NaB) exert neuroprotective effects in various animal models of neurological disorders. Thus, the present study investigated whether VPA or NaB prevent Mn-induced neurotoxicity by assessing locomotor activities and expression of astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST), in C57BL/6 mice...
June 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28450929/effect-of-intranasal-stem-cell-administration-on-the-nigrostriatal-system-in-a-mouse-model-of-parkinson-s-disease
#9
Mohamed Salama, Mahmoud Sobh, Mahmoud Emam, Ahmed Abdalla, Dina Sabry, Mohamed El-Gamal, Ahmed Lotfy, Mahmoud El-Husseiny, Mohamed Sobh, Ali Shalash, Wael My Mohamed
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28436395/phase-iib-study-of-intranasal-glutathione-in-parkinson-s-disease
#10
Laurie K Mischley, Richard C Lau, Eric G Shankland, Timothy K Wilbur, Jeannie M Padowski
BACKGROUND: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson's disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD. OBJECTIVE: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study. METHODS: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1-3 PD...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28385921/the-effects-of-physical-exercise-on-non-motor-symptoms-and-on-neuroimmune-rage-network-in-experimental-parkinsonism
#11
Sofia D Viana, Inês R Pita, Cristina Lemos, Daniel Rial, Patrícia Couceiro, Paulo Rodrigues-Santos, Francisco Caramelo, Félix Carvalho, Syed F Ali, Rui D Prediger, Carlos A Fontes Ribeiro, Frederico C Pereira
Parkinson's disease (PD) prodromic stages comprise neuropsychiatric perturbations that critically compromise patient's quality of life. These non-motor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network including receptors for advanced glycation endproducts (RAGE) and Toll-like receptors (TLRs) in distinct pathological settings. Accordingly, the present study aimed to test the hypothesis that PE i) alleviates PD NMS and ii) modulates neuroimmune RAGE-network in experimental PD...
April 6, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28247332/intranasal-administration-of-gdnf-protects-against-neural-apoptosis-in-a-rat-model-of-parkinson-s-disease-through-pi3k-akt-gsk3%C3%AE-pathway
#12
Peijian Yue, Lin Gao, Xuejing Wang, Xuebing Ding, Junfang Teng
Glial cell line-derived neurotrophic factor (GDNF) plays important roles in protecting the damaged or dying dopamine neurons in the animal models of Parkinson's disease (PD). This study was to determine the effect and mechanisms of GDNF on the apoptosis of neurons in 6-hydroxydopamine (6-OHDA) induced Parkinson's disease model of rats. Healthy male Sprague-Dawley rats (220-240 g) were randomly divided into six groups (n = 10). 6-OHDA was used to establish the PD rat model. Tyrosine hydroxylase (TH) immunohistochemistry was used to assess the neuron loss in 6-OHDA-lesioned rats...
May 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28049942/intranasal-administration-of-rotenone-to-mice-induces-dopaminergic-neurite-degeneration-of-dopaminergic-neurons-in-the-substantia-nigra
#13
Hitoshi Sasajima, Sadaharu Miyazono, Tomohiro Noguchi, Makoto Kashiwayanagi
Exposure to environmental neurotoxins is suspected to be a risk factor for sporadic progressive neurodegenerative diseases. Parkinson's disease has been associated with exposure to the pesticide rotenone, a mitochondrial respiration inhibitor. We previously reported that intranasal administration of rotenone in mice induced dopaminergic (DA) neurodegeneration in the olfactory bulb (OB) and reduced olfactory functions. In the present study, we investigated the DA neurons in the brains of mice that were administered rotenone intranasally for an extended period...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27994458/intranasal-delivery-of-rotigotine-to-the-brain-with-lactoferrin-modified-peg-plga-nanoparticles-for-parkinson-s-disease-treatment
#14
Chenchen Bi, Aiping Wang, Yongchao Chu, Sha Liu, Hongjie Mu, Wanhui Liu, Zimei Wu, Kaoxiang Sun, Youxin Li
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27590141/fasudil-enhances-therapeutic-efficacy-of-neural-stem-cells-in-the-mouse-model-of-mptp-induced-parkinson-s-disease
#15
Yan-Hua Li, Jing-Wen Yu, Jian-Yin Xi, Wen-Bo Yu, Jian-Chun Liu, Qing Wang, Li-Juan Song, Ling Feng, Ya-Ping Yan, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms...
September 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27280392/nose-to-brain-delivery-of-nanoformulations-for-neurotherapeutics-in-parkinson-1-s-disease-defining-the-preclinical-clinical-and-toxicity-issues
#16
Kamla Pathak, Nida Akhtar
BACKGROUND: Parkinson's disease (PD) is depicted as the most prevailed neurodegenerative disease being secondary to the alzheimer's disease. PD is featured by severe dropping of dopamine related neurons present in substantia nigra as well as cytoplasmic inclusions. A number of therapeutic agents are available to treat initial as well as later complications of PD. However, transport of neurotherapeutics into the brain has been a consistent challenge for researchers, because of the existence of blood-brain barrier (BBB)...
June 7, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27228974/human-basic-fibroblast-growth-factor-inhibits-tau-phosphorylation-via-the-pi3k-akt-gsk3%C3%AE-signaling-pathway-in-a-6-hydroxydopamine-induced-model-of-parkinson-s-disease
#17
Peng-Hui Yang, Jian-Xiu Zhu, Ya-Dong Huang, Xian-Ying Zhang, Peng Lei, Ashley I Bush, Qi Xiang, Zhi-Jian Su, Qi-Hao Zhang
BACKGROUND: Basic fibroblast growth factor (bFGF) has been increasingly investigated due to its neuroprotection in neurodegenerative disorders. Because there are still no cures for any of these disorders, it is crucial to identify new therapeutic targets and screen potential drugs. The increased phosphorylation of tau at Ser396 leads to intracellular tau accumulation, which forms neurofibrillary tangles in Parkinson's disease (PD). In this study, neuroprotection by bFGF was observed, and the mechanisms related to its regulation of phosphorylated tau were investigated...
2016: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/27068140/ropinirole-dextran-sulfate-nanoplex-for-nasal-administration-against-parkinson-s-disease-in-silico-molecular-modeling-and-in-vitro-ex-vivo-evaluation
#18
Chandrakantsing Vijaysing Pardeshi, Veena Shailendra Belgamwar
Dextran sulfate sodium (DS) was allowed to interact ionically with ropinirole hydrochloride (ROPI HCl, an anti-Parkinsonian agent) to synthesize self-assembled ROPI-DS nanoplex. The preliminary objective behind ROPI-DS complexation was to enhance the partitioning of ROPI HCl and thereby its encapsulation into nanocarriers and to improve the nasal membrane permeability. Molecular interactions were computed using in silico molecular modeling. Nanoplex were characterized for physicochemical and partitioning behavior...
May 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/26996132/deferoxamine-mediated-up-regulation-of-hif-1%C3%AE-prevents-dopaminergic-neuronal-death-via-the-activation-of-mapk-family-proteins-in-mptp-treated-mice
#19
Chuang Guo, Li-Juan Hao, Zhao-Hui Yang, Rui Chai, Shuai Zhang, Yu Gu, Hui-Ling Gao, Man-Li Zhong, Tao Wang, Jia-Yi Li, Zhan-You Wang
Accumulating evidence suggests that an abnormal accumulation of iron in the substantia nigra (SN) is one of the defining characteristics of Parkinson's disease (PD). Accordingly, the potential neuroprotection of Fe chelators is widely acknowledged for the treatment of PD. Although desferrioxamine (DFO), an iron chelator widely used in clinical settings, has been reported to improve motor deficits and dopaminergic neuronal survival in animal models of PD, DFO has poor penetration to cross the blood-brain barrier and elicits side effects...
June 2016: Experimental Neurology
https://www.readbyqxmd.com/read/26885338/effects-of-l-arginine-pre-treatment-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-parkinson-s-diseases-in-balb-c-mice
#20
Javad Hami, Mehran Hosseini, Sekineh Shahi, Nassim Lotfi, Abolfazl Talebi, Mohammad Afshar
BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage...
October 7, 2015: Iranian Journal of Neurology
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