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https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#1
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28190402/preserving-brain-function-in-a-comatose-patient-with-septic-hyperpyrexia-41-6%C3%A2-%C3%A2-c-a-case-report
#2
Samantha Sterkel, Akinboyede Akinyemi, Marcos A Sanchez-Gonzalez, George Michel
BACKGROUND: Pyrexia is a physiological response through which the immune system responds to infectious processes. Hyperpyrexia is known to be neurodegenerative leading to brain damage. Some of the neurotoxic effects of hyperpyrexia on the brain include seizures, decreased cognitive speed, mental status changes, coma, and even death. In the clinical management of hyperpyrexia, the goal is to treat the underlying cause of elevated temperature and prevent end organ damage. CASE PRESENTATION: This case illustrates a 39-year-old white American man referred from another medical facility where he had undergone an upper gastrointestinal tract diagnostic procedure which became complicated by blood aspiration and respiratory distress...
February 13, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28142208/intravenously-transplanted-human-bone-marrow-endothelial-progenitor-cells-engraft-within-brain-capillaries-preserve-mitochondrial-morphology-and-display-pinocytotic-activity-towards-bbb-repair-in-ischemic-stroke-rats
#3
Svitlana Garbuzova-Davis, Edward Haller, Roger Lin, Cesario V Borlongan
Stroke is a life threatening disease with limited therapeutic options. Cell therapy has emerged as an experimental stroke treatment. Blood-brain barrier (BBB) impairment is a key pathological manifestation of ischemic stroke, and barrier repair is an innovative target for neurorestoration in stroke. Here, we evaluated via electron microscopy the ability of transplanted human bone marrow endothelial progenitor cells (hBMEPCs) to repair the BBB in adult Sprague-Dawley rats subjected to transient middle cerebral artery occlusion (tMCAO)...
January 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28134996/combined-ipsilateral-limb-use-score-as-an-index-of-motor-deficits-and-neurorestoration-in-parkinsonian-rats
#4
Juuso V Leikas, Tiina M Kääriäinen, Aaro J Jalkanen, Marko Lehtonen, Tomi Rantamäki, Markus M Forsberg
Our aim was to apply a robust non-drug induced sensorimotor test battery to assess the efficacy of neurorestorative therapies on the motor deficits caused by partial unilateral 6-OHDA lesion mimicking early stage PD. Since the 6-OHDA lesion protocols to induce partial DA depletion in striatum vary extensively between laboratories, we evaluated the associations between different intrastriatal 6-OHDA doses (1 X 0-20 and 2 X 0-30 µg), striatal DA depletion (HPLC-ECD) and D-amphetamine induced rotation to identify a lesion protocol that would produce 40-60% striatal DA depletion...
January 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28131727/long-term-protective-effects-of-aav9-mesencephalic-astrocyte-derived-neurotrophic-factor-gene-transfer-in-parkinsonian-rats
#5
Fei Hao, Chun Yang, Sha-Sha Chen, Yan-Yan Wang, Wei Zhou, Qiang Hao, Tao Lu, Barry Hoffer, Li-Ru Zhao, Wei-Ming Duan, Qun-Yuan Xu
Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28102082/characterization-of-the-molecular-mechanisms-underlying-the-chronic-phase-of-stroke-in-a-cynomolgus-monkey-model-of-induced-cerebral-ischemia
#6
Henry C H Law, Samuel S W Szeto, Quan Quan, Yun Zhao, Zaijun Zhang, Olga Krakovska, Leong Ting Lui, Chengyou Zheng, Simon Ming Yuen Lee, K W Michael Siu, Yuqiang Wang, Ivan K Chu
Stroke is one of the main causes of mortality and long-term disability worldwide. The pathophysiological mechanisms underlying this disease are not well understood, particularly in the chronic phase after the initial ischemic episode. In this study, a Macaca fascicularis stroke model consisting of two sample groups, as determined by MRI-quantified infarct volumes as a measure of the stroke severity 28 days after the ischemic episode, was evaluated using qualitative and quantitative proteomics analyses. By using multiple online multidimensional liquid chromatography platforms, 8790 non-redundant proteins that condensed to 5223 protein groups at 1% global false discovery rate (FDR)...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28088914/diverse-functions-and-mechanisms-of-pericytes-in-ischemic-stroke
#7
Shuai Yang, Huijuan Jin, Yiyi Zhu, Yan Wan, Lingqiang Zhu, Bo Hu
Pericytes are mural cells embedded in the basement membrane of microvessels. Because of such a unique position in the blood-brain barrier (BBB) and neurovascular unit (NVU), they receive, orchestrate and process signals from their neighboring cells to generate diverse neurovascular functions, including regulation of capillary hemodynamics, BBB permeability, clearance of toxic metabolites, angiogenesis, neuroinflammation and stem cell activity. During the different stages of ischemic stroke, pericytes play different roles: 1) On the hyperacute phase of stroke, pericytes constriction and death may be a cause of the no-reflow phenomenon in brain capillaries; 2) During the acute phase, pericytes detach from microvessels and participate in inflammatory-immunological response, resulting in the BBB damage and brain edema...
January 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28028143/abca1-apoe-hdl-pathway-mediates-gw3965-induced-neurorestoration-after-stroke
#8
Xu Cui, Michael Chopp, Zhenggang Zhang, Rongwen Li, Alex Zacharek, Julie Landschoot-Ward, Poornima Venkat, Jieli Chen
BACKGROUND AND PURPOSE: ATP-binding cassette transporter A1 (ABCA1) is a major reverse cholesterol transporter and plays critical role in the formation of brain high-density lipoprotein (HDL) cholesterol. Apolipoprotein E (ApoE) is the most abundant apolipoprotein and transports cholesterol into cells in brain. ABCA1 and ApoE are upregulated by liver-X receptors. Activation of liver-X receptors has neurorestorative benefit for stroke. The current study investigates whether ABCA1/ApoE/HDL pathway mediates GW3965, a synthetic dual liver-X receptor agonist, induced neurorestoration after stroke...
February 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27920671/proceedings-of-the-fourth-annual-deep-brain-stimulation-think-tank-a-review-of-emerging-issues-and-technologies
#9
Wissam Deeb, James J Giordano, Peter J Rossi, Alon Y Mogilner, Aysegul Gunduz, Jack W Judy, Bryan T Klassen, Christopher R Butson, Craig Van Horne, Damiaan Deny, Darin D Dougherty, David Rowell, Greg A Gerhardt, Gwenn S Smith, Francisco A Ponce, Harrison C Walker, Helen M Bronte-Stewart, Helen S Mayberg, Howard J Chizeck, Jean-Philippe Langevin, Jens Volkmann, Jill L Ostrem, Jonathan B Shute, Joohi Jimenez-Shahed, Kelly D Foote, Aparna Wagle Shukla, Marvin A Rossi, Michael Oh, Michael Pourfar, Paul B Rosenberg, Peter A Silburn, Coralie de Hemptine, Philip A Starr, Timothy Denison, Umer Akbar, Warren M Grill, Michael S Okun
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome...
2016: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/27915043/involvement-of-bdnf-trkb-signaling-in-the-effect-of-diphenyl-diselenide-on-motor-function-in-a-parkinson-s-disease-rat-model
#10
Tuane Bazanella Sampaio, Simone Pinton, Juliana Trevisan da Rocha, Bibiana Mozzaquatro Gai, Cristina Wayne Nogueira
Parkinson's disease is a progressive neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons. Diphenyl diselenide [(PhSe)2] is a compound with pharmacological proprieties, such as antidepressant and neuroprotective. Therefore, this study investigated whether (PhSe)2 reverses motor impairment and neurochemical alterations in a model of Parkinson's disease induced by 6-hydroxydopamine (6-OHDA) in rats. For this, male Wistar rats received 20μg/3μl of 6-OHDA or vehicle into the right striatum...
December 1, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27846631/prognostic-factors-and-pattern-of-long-term-recovery-with-mlc601-neuroaid%C3%A2-in-the-chinese-medicine-neuroaid-efficacy-on-stroke-recovery-extension-study
#11
Narayanaswamy Venketasubramanian, Chun Fan Lee, Sherry H Young, San San Tay, Thirugnanam Umapathi, Annabelle Y Lao, Herminigildo H Gan, Alejandro C Baroque Ii, Jose C Navarro, Hui Meng Chang, Joel M Advincula, Sombat Muengtaweepongsa, Bernard P L Chan, Carlos L Chua, Nirmala Wijekoon, H Asita de Silva, John Harold B Hiyadan, Nijasri C Suwanwela, K S Lawrence Wong, Niphon Poungvarin, Gaik Bee Eow, Christopher L H Chen
BACKGROUND: The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. METHODS: The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months...
2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27844282/morphological-changes-in-a-severe-model-of-parkinson-s-disease-and-its-suitability-to-test-the-therapeutic-effects-of-microencapsulated-neurotrophic-factors
#12
C Requejo, J A Ruiz-Ortega, H Bengoetxea, A García-Blanco, E Herrán, A Aristieta, M Igartua, J L Pedraz, L Ugedo, R M Hernández, J V Lafuente
The unilateral 6-hydroxydopamine (6-OHDA) lesion of medial forebrain bundle (MFB) in rats affords us to study the advanced stages of Parkinson's disease (PD). Numerous evidences suggest synergic effects when various neurotrophic factors are administered in experimental models of PD. The aim of the present work was to assess the morphological changes along the rostro-caudal axis of caudo-putamen complex and substantia nigra (SN) in the referred model in order to test the suitability of a severe model to evaluate new neurorestorative therapies...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27833029/bdnf-pi3k-akt-and-nogo-a-rhoa-rock-signaling-pathways-contribute-to-neurorestorative-effect-of-houshiheisan-against-cerebral-ischemia-injury-in-rats
#13
Jiahui Chang, Xiaoquan Yao, Haiyan Zou, Lei Wang, Yue Lu, Qiuxia Zhang, Hui Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: Houshiheisan (HSHS), a classic traditional medicine prescription, has notable effects on patients with stroke AIM OF THE STUDY: To investigate the neurorestorative effects of HSHS on ischemic stroke and explore its mode of action. MATERIALS AND METHODS: Focal cerebral ischemia models were induced by permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley (SD) rats were randomly divided into 5 experimental groups: sham vehicle, ischemia vehicle, pMCAO+HSHS at 5...
December 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27794200/ellagic-acid-improves-endogenous-neural-stem-cells-proliferation-and-neurorestoration-through-wnt-%C3%AE-catenin-signaling-in-vivo-and-in-vitro
#14
Qing-Shan Liu, Shu-Ran Li, Keqin Li, Xu Li, Xiaoying Yin, Zongran Pang
SCOPE: The aim of this study is to research the effects of the polyphenol ellagic acid (EA) on brain cells and to explore its mechanism of action, and to evaluate whether EA can be safely utilized by humans as a functional food or therapeutic agent. METHODS AND RESULTS: A photothrombosis-induced model of brain injury in rats was created, and EA was administered intragastrically to rats on 7 consecutive days post-venous ischemia. An oxygen-glucose deprivation and re-perfusion model was established in neural stem cells in order to research the effects on proliferation after 2 days of EA treatment in vitro...
October 29, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27729575/neurorestorative-responses-to-delayed-human-mesenchymal-stromal-cells-treatment-of-stroke-in-type-2-diabetic-rats
#15
Tao Yan, Poornima Venkat, Michael Chopp, Alex Zacharek, Ruizhuo Ning, Cynthia Roberts, Yi Zhang, Mei Lu, Jieli Chen
BACKGROUND AND PURPOSE: Comorbidity of diabetes mellitus and stroke results in worse functional outcome, poor long-term recovery, and extensive vascular damage. We investigated the neurorestorative effects and mechanisms of stroke treatment with human bone marrow-derived mesenchymal stromal cells (hMSCs) in type 2 diabetes mellitus (T2DM) rats. METHODS: Adult male Wistar rats were induced with T2DM, subjected to 2 hours of middle cerebral artery occlusion (MCAo) and treated via tail-vein injection with (1) PBS (n=8) and (2) hMSCs (n=10; 5×10(6)) at 3 days after MCAo...
November 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27689101/expression-mediated-by-three-partial-sequences-of-the-human-tyrosine-hydroxylase-promoter-in-vivo
#16
Anne-Sophie Rolland, Tatyana Kareva, Olga Yarygina, Nikolai Kholodilov, Robert E Burke
The use of viral vectors to transfect postmitotic neurons has provided an important research tool, and it offers promise for treatment of neurologic disease. The utility of vectors is enhanced by the use of selective promoters that permit control of the cellular site of expression. One potential clinical application is in the neurorestorative treatment of Parkinson's disease by the induction of new axon growth. However, many of the genes with an ability to restore axons have oncogenic potential. Therefore, clinical safety would be enhanced by restriction of expression to neurons affected by the disease, particularly dopamine neurons...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27677185/lipoic-acid-use-and-functional-outcomes-after-thrombolysis-in-patients-with-acute-ischemic-stroke-and-diabetes
#17
Kang-Ho Choi, Man-Seok Park, Joon-Tae Kim, Hyung-Seok Kim, Ja-Hae Kim, Tai-Seung Nam, Seong-Min Choi, Seung-Han Lee, Byeong-Chae Kim, Myeong-Kyu Kim, Ki-Hyun Cho
BACKGROUND: Alpha-lipoic acid (aLA) is a strong antioxidant commonly used for treating diabetic polyneuropathy. Previously, we demonstrated the neurorestorative effects of aLA after cerebral ischemia in rats. However, its effects on patients with stroke remain unknown. We investigated whether patients treated with aLA have better functional outcomes after acute ischemic stroke (AIS) and reperfusion therapy than patients not receiving aLA. METHODS: In this retrospective study of 172 prospectively registered patients with diabetes and AIS treated with tissue plasminogen activator (tPA), we investigated the relationship between aLA use and functional outcome both after 3 months and after 1 year...
2016: PloS One
https://www.readbyqxmd.com/read/27633784/merging-transport-data-for-choroid-plexus-with-blood-brain-barrier-to-model-cns-homeostasis-and-diseases-more-effectively
#18
Conrad Johanson, Nancy Johanson
Robust modeling of CNS transport integrates molecular fluxes at the microvascular blood-brain barrier and epithelial choroid plexus blood-CSF barrier. Normal activity of solute transporters, channels and aquaporins, in the cerebral endothelium and choroidal epithelium, sets the microenvironment composition for neurons and glia. Conversely, perturbed transport/permeability at the barrier interfaces causes interstitial fluid dyshomeostasis (e.g. edema) arising in neural disorders. Critically-important transependymal solute/water distribution between brain and CSF needs more attention...
September 15, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27614933/sildenafil-improves-brain-injury-recovery-following-term-neonatal-hypoxia-ischemia-in-male-rat-pups
#19
Armin Yazdani, Zehra Khoja, Aaron Johnstone, Laura Dale, Emmanouil Rampakakis, Pia Wintermark
Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control...
2016: Developmental Neuroscience
https://www.readbyqxmd.com/read/27592819/safety-and-tolerability-of-silk-fibroin-hydrogels-implanted-into-the-mouse-brain
#20
Laura Fernández-García, Núria Marí-Buyé, Juan A Barios, Rodrigo Madurga, Manuel Elices, José Pérez-Rigueiro, Milagros Ramos, Gustavo V Guinea, Daniel González-Nieto
: At present, effective therapies to repair the central nervous system do not exist. Biomaterials might represent a new frontier for the development of neurorestorative therapies after brain injury and degeneration. In this study, an in situ gelling silk fibroin hydrogel was developed via the sonication-induced gelation of regenerated silk fibroin solutions. An adequate timeframe for the integration of the biomaterial into the brain tissue was obtained by controlling the intensity and time of sonication...
November 2016: Acta Biomaterialia
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