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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...
October 11, 2016: Stroke; a Journal of Cerebral Circulation
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
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
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
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...
September 10, 2016: Developmental Neuroscience
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
Jing-Wen Yu, Yan-Hua Li, Guo-Bin Song, Jie-Zhong Yu, Chun-Yun Liu, Jian-Chun Liu, Hai-Fei Zhang, Wan-Fang Yang, Qing Wang, Ya-Ping Yan, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived mesenchymal stem cells (MSCs) are the ideal transplanted cells of cellular therapy for promoting neuroprotection and neurorestoration. However, the optimization of transplanted cells and the improvement of microenvironment around implanted cells are still two critical challenges for enhancing therapeutic effect. In the current study, we observed the therapeutic potential of MSCs combined with Fasudil in mouse model of experimental autoimmune encephalomyelitis (EAE) and explored possible mechanisms of action...
August 30, 2016: Journal of Molecular Neuroscience: MN
G Grolez, C Moreau, V Danel-Brunaud, C Delmaire, R Lopes, P F Pradat, M M El Mendili, L Defebvre, D Devos
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that mainly affects the motor system. A number of potentially neuroprotective and neurorestorative disease-modifying drugs are currently in clinical development. At present, the evaluation of a drug's clinical efficacy in ALS is based on the ALS Functional Rating Scale Revised, motor tests and survival. However, these endpoints are general, variable and late-stage measures of the ALS disease process and thus require the long-term assessment of large cohorts...
2016: BMC Neurology
Anne Kastner, Valéry Matarazzo
High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways...
2016: Neural Plasticity
Tomás Herraiz
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium cation (MPP(+)) are selective dopaminergic neurotoxins producing Parkinsonism. MPTP is activated by monoamine oxidase-B (MAO-B) to MPP(+) that inhibits mitochondrial function. Molecules resembling MPTP which afford pyridinium cations are also neurotoxins. The herbicide paraquat (a bipyridinium dication) and the naturally-occurring β-carboline and isoquinoline alkaloids are structural analogues of MPTP/MPP(+). Paraquat generates reactive oxygen species (ROS) producing neurotoxicity by a mechanism that differs from MPTP/MPP(+)...
August 11, 2016: Food and Chemical Toxicology
Chengcheng Cui, Xinchun Ye, Michael Chopp, Poornima Venkat, Alex Zacharek, Tao Yan, Ruizhou Ning, Peng Yu, Guiyun Cui, Jieli Chen
: : In rats with type 1 diabetes (T1DM), the therapeutic effects and underlying mechanisms of action of stroke treatment were compared between bone-marrow stromal cells (BMSCs) derived from T1DM rats (DM-BMSCs) and BMSCs derived from normal rats (Nor-BMSCs). The novel role of microRNA-145 (miR-145) in mediating DM-BMSC treatment-induced benefits was also investigated. T1DM rats (n = 8 per group) underwent 2 hours of middle cerebral artery occlusion (MCAo) and were treated 24 hours later with the one of the following (5 × 10(6) cells administered i...
July 26, 2016: Stem Cells Translational Medicine
Mohammed Aftab Alam, V P Subramanyam Rallabandi, Prasun K Roy
AIMS: Recent studies indicate that anti-inflammatory drugs, act as a double-edged sword, not only exacerbating secondary brain injury but also contributing to neurological recovery after stroke. Our aim is to explore whether there is a beneficial role for neuroprotection and functional recovery using anti-inflammatory drug along with neurorehabilitation therapy using transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), so as to improve functional recovery after ischemic stroke...
2016: Frontiers in Neurology
Jaishree Jalewa, Mohit Kumar Sharma, Christian Hölscher
Currently, there is no viable treatment available for Parkinson's disease (PD) that stops or reverses disease progression. Interestingly, studies testing the glucagon-like-peptide-1 (GLP-1) mimetic Exendin-4 have shown neuroprotective/neurorestorative properties in pre-clinical tests and in a pilot clinical study of PD. Incretin analogues were originally developed to treat type 2 diabetes and several are currently on the market. In this study, we tested novel incretin analogues on the dopaminergic SH-SY5Y neuroblastoma cells against a toxic mitochondrial complex I inhibitor, Rotenone...
October 2016: Journal of Neurochemistry
Zoltán Rusznák, Willem Henskens, Emma Schofield, Woojin S Kim, YuHong Fu
The subgranular zone (SGZ) and subventricular zone (SVZ) are developmental remnants of the germinal regions of the brain, hence they retain the ability to generate neuronal progenitor cells in adult life. Neurogenesis in adult brain has an adaptive function because newly produced neurons can integrate into and modify existing neuronal circuits. In contrast to the SGZ and SVZ, other brain regions have a lower capacity to produce new neurons, and this usually occurs via parenchymal and periventricular cell genesis...
June 2016: Experimental Neurobiology
Marco Musilli, Maria Teresa Ciotti, Massimo Pieri, Assunta Martino, Sonia Borrelli, Vincenzo Dinallo, Giovanni Diana
Recent evidence suggests an early involvement of dopaminergic (DA) processes and terminals in Parkinson's disease (PD). The arborization of neurons depends on the actin cytoskeleton, which in turn is regulated by small GTPases of the Rho family, encompassing Rho, Rac and Cdc42 subfamilies. Indeed, some reports point to a role for Rac and Cdc42 signaling in the pathophysiology of inherited parkinsonisms. We thus investigated the potential therapeutic effect of the modulation of cerebral Rho GTPases in PD. Cytotoxic necrotizing factor 1 (CNF1), a 114 kDa protein toxin produced by Escherichia coli, permanently activates RhoA, Rac1 and Cdc42 in intact cells...
October 2016: Neuropharmacology
Rebecca L Hood, William A Liguore, Cynthia Moore, Lacey Pflibsen, Charles K Meshul
While exercise is commonly recommended for PD patients to improve motor function, little is known about the disease-altering potential of exercise. Although others have demonstrated neuroprotective or neurorestorative effects of exercise in animal models of PD, the majority of these studies utilize young animals. In order to assess the effects of exercise intervention in a more clinically relevant model, we have subjected aged mice to progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning and daily treadmill exercise, initiated early in the course of the disease...
September 1, 2016: Brain Research
Ahmet Hilmi Kaya, Hakan Erdogan, Erol Tasdemiroglu
So far, animal models have helped us better understand the pathophysiology of the ischemic brain damage but they could not contribute so much to clinical practice. The discrepancies in results regarding neuroprotective agents in animal experiments compared to clinical trials has not been solved. Various animal models of ischemic stroke have proven efficacy of many neuroprotective agents without any considerable result in phase III clinical trials. As it is well known, stroke related focal cerebral ischemia or cardiac arrest related global cerebral ischemia are major causes of disability and death among human subjects...
March 28, 2016: Turkish Neurosurgery
Wei Liu, Ming Lang, Moussa B H Youdim, Tamar Amit, Yewei Sun, Zaijun Zhang, Yuqiang Wang, Orly Weinreb
Current novel therapeutic approach suggests that multifunctional compounds with diverse biological properties and a single bioavailability and pharmacokinetic metabolism, will produce higher significant advantages in treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Based on this rational, a new class of cholinesterase (ChE)-monoamine oxidase (MAO) inhibitors were designed and synthesized by amalgamating the propargyl moiety of the irreversible selective MAO-B inhibitor, neuroprotective/neurorestorative anti-Parkinsonian drug, rasagiline, into the "N-methyl" position of the ChE inhibitor, anti-AD drug rivastigmine...
October 2016: Neuropharmacology
Francesco Bez, Veronica Francardo, M Angela Cenci
Mice with striatal 6-hydroxydopamine (6-OHDA) lesions are widely used as a model to study the effects of neurorestorative, symptomatic, or antidyskinetic treatments for Parkinson's disease (PD). The standard praxis is to utilize young adult mice with relatively acute 6-OHDA lesions. However, long post-lesion intervals may be required for longitudinal studies of treatment interventions, and the long-term stability of the model's behavioral and cellular phenotypes is currently unknown. In this study, C57Bl/6J mice sustained unilateral striatal 6-OHDA lesions at approx...
October 2016: Neurobiology of Disease
Ahmed Alhusban, Anna Kozak, Wael Eldahshan, Adviye Ergul, Susan C Fagan
[This corrects the article DOI: 10.1186/s13231-016-0018-x.].
2016: Experimental & Translational Stroke Medicine
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