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Parkinson disease and intranasal

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https://www.readbyqxmd.com/read/29338427/lipid-nanoparticles-for-intranasal-administration-application-to-nose-to-brain-delivery
#1
Luigi Battaglia, Pier Paolo Panciani, Elisabetta Muntoni, Maria Teresa Capucchio, Elena Biasibetti, Pasquale De Bonis, Silvia Mioletti, Marco Fontanella, Shankar Swaminathan
The blood brain barrier is a functional barrier allowing the entry into the brain of only essential nutrients, excluding other molecules. Its structure, although essential to keep the harmful entities out, is also a major roadblock for pharmacological treatment of brain diseases. Several alternative invasive drug delivery approaches, such as transcranial drug delivery and disruption of blood brain barrier have been explored, with limited success and several challenges. Intranasal delivery is a non-invasive methodology, which bypasses the systemic circulation, and, through the intra- and extra- neuronal pathways, provides direct brain drug delivery...
January 17, 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29327206/brain-photobiomodulation-therapy-a-narrative-review
#2
REVIEW
Farzad Salehpour, Javad Mahmoudi, Farzin Kamari, Saeed Sadigh-Eteghad, Seyed Hossein Rasta, Michael R Hamblin
Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29295587/dopamine-and-levodopa-prodrugs-for-the-treatment-of-parkinson-s-disease
#3
REVIEW
Fatma Haddad, Maryam Sawalha, Yahya Khawaja, Anas Najjar, Rafik Karaman
Background: Parkinson's disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals...
December 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29273501/selective-%C3%AE-synuclein-knockdown-in-monoamine-neurons-by-intranasal-oligonucleotide-delivery-potential-therapy-for-parkinson-s-disease
#4
Diana Alarcón-Arís, Ariadna Recasens, Mireia Galofré, Iria Carballo-Carbajal, Nicolás Zacchi, Esther Ruiz-Bronchal, Rubén Pavia-Collado, Rosario Chica, Albert Ferrés-Coy, Marina Santos, Raquel Revilla, Andrés Montefeltro, Isabel Fariñas, Francesc Artigas, Miquel Vila, Analia Bortolozzi
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson's disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration...
November 29, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29247729/pramipexole-dihydrochloride-loaded-chitosan-nanoparticles-for-nose-to-brain-delivery-development-characterization-and-in-vivo-anti-parkinson-activity
#5
Ruhi Raj, Sarika Wairkar, Vinay Sridhar, Ram Gaud
In the current study, Pramipexole dihydrochloride loaded chitosan nanoparticles (P-CNs) were prepared for Parkinson's disease via nose to brain pathway by ionic gelation method. Optimized P-CNs with chitosan and sodium tripolyphosphate (6:1 v/v) exhibited particle size and entrapment efficiency of 292.5 nm ± 8.80 and 91.25% ± 0.95 respectively and its diffusion across the artificial membrane and goat nasal mucosa was found to be 93.32% ± 2.56 and 83.03% ± 3.48 correspondingly after 24 h...
December 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29181847/achyranthes-bidentata-polypeptide-protects-dopaminergic-neurons-from-apoptosis-in-parkinson-s-disease-models-both-in-vitro-and-in-vivo
#6
Su Peng, Caiping Wang, Jinyu Ma, Ketao Jiang, Yuhui Jiang, Xiaosong Gu, Cheng Sun
BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder closely associated with dopaminergic neuron loss. It is well documented that Achyranthes bidentata polypeptides (ABPP) are potent neuroprotective agents in several kinds of neurons. Therefore, we predicted that ABPP might play a beneficial role against PD by protecting dopaminergic neurons from apoptosis. EXPERIMENTAL APPROACH: The SH-SY5Y cells and primary rat dopaminergic neurons were pretreated with ABPPk, a purified fraction of ABPP, and then the cells were exposure to MPP+ to induce apoptosis...
November 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29181664/immunomorphological-changes-in-the-olfactory-bulbs-of-rats-after-intranasal-administration-of-rotenone
#7
D N Voronkov, K A Kutukova, M V Ivanov, R M Khudoerkov
Changes in the structure of the olfactory bulbs after long-term intranasal administration of pesticide rotenone, a classical inductor of parkinsonism, to rats were studied by the methods of immunomorphology. In rats intranasally receiving rotenone in a dose of 2.5 mg/kg every other day over 2 weeks, a decrease in the density of dopaminergic neurons and the area of astrocyte processes in the olfactory bulbs, activation of microglia in the glomerular layer, and enhanced α-synuclein phosphorylation and its accumulation in the bodies of mitral layer neurons were observed...
November 27, 2017: Bulletin of Experimental Biology and Medicine
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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