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https://www.readbyqxmd.com/read/29896433/apx3330-promotes-neurorestorative-effects-after-stroke-in-type-one-diabetic-rats
#1
Tao Yan, Poornima Venkat, Michael Chopp, Alex Zacharek, Peng Yu, Ruizhuo Ning, Xiaoxi Qiao, Mark R Kelley, Jieli Chen
APX3330 is a selective inhibitor of APE1/Ref-1 redox activity. In this study, we investigate the therapeutic effects and underlying mechanisms of APX3330 treatment in type one diabetes mellitus (T1DM) stroke rats. Adult male Wistar rats were induced with T1DM and subjected to transient middle cerebral artery occlusion (MCAo) and treated with either PBS or APX3330 (10mg/kg, oral gavage) starting at 24h after MCAo, and daily for 14 days. Rats were sacrificed at 14 days after MCAo and, blood brain barrier (BBB) permeability, ischemic lesion volume, immunohistochemistry, cell death assay, Western blot, real time PCR, and angiogenic ELISA array were performed...
June 2018: Aging and Disease
https://www.readbyqxmd.com/read/29895906/repositioning-of-omarigliptin-as-a-once-weekly-intranasal-anti-parkinsonian-agent
#2
Bassam M Ayoub, Shereen Mowaka, Marwa M Safar, Nermeen Ashoush, Mona G Arafa, Haidy E Michel, Mariam M Tadros, Mohamed M Elmazar, Shaker A Mousa
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work...
June 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29895321/neural-stem-cell-therapy-for-subacute-and-chronic-ischemic-stroke
#3
REVIEW
Austin C Boese, Quan-Son Eric Le, Dylan Pham, Milton H Hamblin, Jean-Pyo Lee
Neural stem cells (NSCs) play vital roles in brain homeostasis and exhibit a broad repertoire of potentially therapeutic actions following neurovascular injury. One such injury is stroke, a worldwide leading cause of death and disability. Clinically, extensive injury from ischemic stroke results from ischemia-reperfusion (IR), which is accompanied by inflammation, blood-brain barrier (BBB) damage, neural cell death, and extensive tissue loss. Tissue plasminogen activator (tPA) is still the only US Food and Drug Administration-approved clot-lysing agent...
June 13, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29888985/exosome-mediated-amplification-of-endogenous-brain-repair-mechanisms-and-brain-and-systemic-organ-interaction-in-modulating-neurological-outcome-after-stroke
#4
Poornima Venkat, Jieli Chen, Michael Chopp
Ischemic stroke is caused by a regional interruption of cerebral blood flow to the brain. Rigorous pre-clinical and clinical research has made landmark progress in stroke treatment using thrombolytics and endovascular thrombectomy. Although numerous successful neuroprotective therapeutic agents for ischemic stroke have been reported in pre-clinical studies, most of them failed in clinical testing. Persistent pre-clinical research has demonstrated that the ischemic brain is not only passively dying but is also actively recovering...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29871521/stem-cell-therapy-a-promising-therapeutic-method-for-intracerebral-hemorrhage
#5
Liansheng Gao, Weilin Xu, Tao Li, Jingyin Chen, Anwen Shao, Feng Yan, Gao Chen
BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. METHODS: In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29857941/gdnf-revisited-a-novel-mammalian-cell-derived-variant-form-of-gdnf-increases-dopamine-turnover-and-improves-brain-biodistribution
#6
REVIEW
Richard Grondin, O Meagan Littrell, Zhiming Zhang, Yi Ai, Peter Huettl, Francois Pomerleau, Jorge E Quintero, Anders H Andersen, Mallory J Stenslik, Luke H Bradley, Jack Lemmon, Michael J O'Neill, Don M Gash, Greg A Gerhardt
Parkinson's disease (PD) is a disorder affecting dopamine neurons for which there is no cure. Glial cell line-derived neurotrophic factor (GDNF) and the closely related protein neurturin are two trophic factors with demonstrated neuroprotective and neurorestorative properties on dopamine neurons in multiple animal species. However, GDNF and neurturin Phase-2 clinical trials have failed to demonstrate a significant level of improvement over placebo controls. Insufficient drug distribution in the brain parenchyma has been proposed as a major contributing factor for the lack of clinical efficacy in the Phase-2 trial patients...
May 29, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29808778/a-mild-traumatic-brain-injury-in-mice-produces-lasting-deficits-in-brain-metabolism
#7
Danielle N Lyons, Hemendra Vekaria, Teresa Macheda, Vikas Bakshi, David K Powell, Brian T Gold, Ai-Ling Lin, Pat Sulllivan, Adam D Bachstetter
Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (ATP production) and state-V (complex-I) driven mitochondrial respiration was found at 1-month post-injury in adult C57Bl/6J mice...
May 29, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29807056/advances-in-stroke-pharmacology
#8
REVIEW
Zhenhua Zhou, Jianfei Lu, Wen-Wu Liu, Anatol Manaenko, Xianhua Hou, Qiyong Mei, Jun-Long Huang, Jiping Tang, John H Zhang, Honghong Yao, Qin Hu
Stroke occurs when a cerebral blood vessel is blocked or ruptured, and it is the major cause of death and adult disability worldwide. Various pharmacological agents have been developed for the treatment of stroke either through interrupting the molecular pathways leading to neuronal death or enhancing neuronal survival and regeneration. Except for rtPA, few of these agents have succeeded in clinical trials. Recently, with the understanding of the pathophysiological process of stroke, there is a resurrection of research on developing neuroprotective agents for stroke treatment, and novel molecular targets for neuroprotection and neurorestoration have been discovered to predict or offer clinical benefits...
May 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29785638/intermittent-convection-enhanced-delivery-of-gdnf-into-rhesus-monkey-putamen-absence-of-local-or-cerebellar-toxicity
#9
Matthias Luz, Philip C Allen, John Bringas, Chris Boiko, Diane E Stockinger, Kristen J Nikula, Owen Lewis, Max Woolley, H Christian Fibiger, Krystof Bankiewicz, Erich Mohr
Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions...
May 22, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29774769/serum-mediated-activation-of-bone-marrow-derived-mesenchymal-stem-cells-in-ischemic-stroke-patients-a-novel-preconditioning-method
#10
Gyeong Joon Moon, Yeon Hee Cho, Dong Hee Kim, Ji Hee Sung, Jeong Pyo Son, Sooyoon Kim, Jae Min Cha, Oh Young Bang
Stroke induces complex and dynamic, local and systemic changes including inflammatory reactions, immune responses, and repair and recovery processes. Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. We hypothesized that serum factors play a critical role in the activation of bone marrow (BM) MSCs after stroke such as by increasing proliferation, paracrine effects, and rejuvenation. Human MSCs (hMSCs) were grown in fetal bovine serum (FBS), normal healthy control serum (NS), or stroke patient serum (SS)...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29774062/-in-vivo-imaging-biomarkers-of-neuroinflammation-in-the-development-and-assessment-of-stroke-therapies-towards-clinical-translation
#11
REVIEW
Bastian Zinnhardt, Maximilian Wiesmann, Lisa Honold, Cristina Barca, Michael Schäfers, Amanda J Kiliaan, Andreas H Jacobs
Modulation of the inflammatory microenvironment after stroke opens a new avenue for the development of novel neurorestorative therapies in stroke. Understanding the spatio-temporal profile of (neuro-)inflammatory imaging biomarkers in detail thereby represents a crucial factor in the development and application of immunomodulatory therapies. The early integration of quantitative molecular imaging biomarkers in stroke drug development may provide key information about (i) early diagnosis and follow-up, (ii) spatio-temporal drug-target engagement (pharmacodynamic biomarker), (iii) differentiation of responders and non-responders in the patient cohort (inclusion/exclusion criteria; predictive biomarkers), and (iv) the mechanism of action...
2018: Theranostics
https://www.readbyqxmd.com/read/29772556/perinatal-brain-injury-mechanisms-and-therapeutic-approaches
#12
Joanne O Davidson, Justin M Dean, Mhoyra Fraser, Guido Wassink, Ted C Andelius, Simerdeep K Dhillon, Laura Bennet, Alistair Jan Gunn
Brain damage resulting from perinatal hypoxia-ischemia evolves slowly over time. While a small number of brain cells may die during a sufficiently profound period of hypoxia-ischemia, many will show initial recovery during a "latent" phase characterized by actively suppressed neural metabolism and activity. Critically, this transient recovery may be followed after ~6 hours by a phase of secondary deterioration, with delayed seizures, failure of mitochondrial function, cytotoxic edema, and bulk cell death over ~72 hours...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29760724/adult-neural-stem-cells-basic-research-and-production-strategies-for-neurorestorative-therapy
#13
REVIEW
E M Samoilova, V A Kalsin, N M Kushnir, D A Chistyakov, A V Troitskiy, V P Baklaushev
Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29722322/treatment-with-acetyl-l-carnitine-exerts-a-neuroprotective-effect-in-the-sciatic-nerve-following-loose-ligation-a-functional-and-microanatomical-study
#14
Daniele Tomassoni, Lorenzo Di Cesare Mannelli, Vincenzo Bramanti, Carla Ghelardini, Francesco Amenta, Alessandra Pacini
Peripheral neuropathies are chronic painful syndromes characterized by allodynia, hyperalgesia and altered nerve functionality. Nerve tissue degeneration represents the microanatomical correlate of peripheral neuropathies. Aimed to improve the therapeutic possibilities, this study investigated the hypersensitivity and the neuromorphological alterations related to the loose ligation of the sciatic nerve in rats. Effects elicited by treatment with acetyl-L-carnitine (ALCAR) in comparison to gabapentin were assessed...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29722303/harnessing-migraines-for-neural-regeneration
#15
REVIEW
Jonathan M Borkum
The success of naturalistic or therapeutic neuroregeneration likely depends on an internal milieu that facilitates the survival, proliferation, migration, and differentiation of stem cells and their assimilation into neural networks. Migraine attacks are an integrated sequence of physiological processes that may protect the brain from oxidative stress by releasing growth factors, suppressing apoptosis, stimulating neurogenesis, encouraging mitochondrial biogenesis, reducing the production of oxidants, and upregulating antioxidant defenses...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29671294/standard-of-care-controversies-and-innovations-in-the-medical-treatment-of-severe-traumatic-brain-injury-stbi
#16
Alba Scerrati, Silvia De Rosa, Lorenzo Mongardi, Michele A Cavallo, Giorgio Trapella, Pasquale De Bonis
Severe traumatic brain injury (STBI) is characterized by a primary injury which cannot be reversed and a secondary injury that can be prevented or reversed. Management of STBI patients in intensive care mainly aims at preventing the secondary injury. Treatment aims to: reducing ICP pressure (that can result in an ischemic insult); avoiding hypotension, hyperthermia, or hypoxemia; maintaining a normal electrolytes homeostasis; treating the Autonomic dysfunction syndrome, coagulopathies, Acute Kidney Injury and maintaining an adequate nutrition...
April 18, 2018: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/29670079/upregulation-of-neuronal-astrocyte-elevated-gene-1-protects-nigral-dopaminergic-neurons-in-vivo
#17
Eunju Leem, Hyung-Jun Kim, Minji Choi, Sehwan Kim, Yong-Seok Oh, Kea Joo Lee, Young-Shik Choe, Jae-Young Um, Won-Ho Shin, Jae Yeong Jeong, Byung Kwan Jin, Dong Woon Kim, Catriona McLean, Paul B Fisher, Nikolai Kholodilov, Kwang Seok Ahn, Jae Man Lee, Un Ju Jung, Seok-Geun Lee, Sang Ryong Kim
The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29661608/modafinil-alleviates-levodopa-induced-excessive-nighttime-sleepiness-and-restores-monoaminergic-systems-in-a-nocturnal-animal-model-of-parkinson-s-disease
#18
Rina Ando, Mohammed Emamussalehin Choudhury, Yuki Yamanishi, Win Thiri Kyaw, Madoka Kubo, Mariko Kannou, Noriko Nishikawa, Junya Tanaka, Masahiro Nomoto, Masahiro Nagai
Treatment with dopaminergic agents result excessive daytime sleepiness (EDS) and some studies have shown the benefit of using modafinil for treating excessive daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether modafinil have ameliorative properties against levodopa induced excessive nighttime sleepiness (ENS) in MPTP-treated murine nocturnal PD model. Our EEG analyses of whole day recordings revealed that modafinil reduce ENS of this nocturnal PD models with levodopa medications...
April 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29618068/occipital-artery-to-posterior-cerebral-artery-bypass-using-descending-branch-of-the-lateral-circumflex-femoral-artery-graft-for-treatment-of-fusiform-unruptured-posterior-cerebral-artery-aneurysm-3-dimensional-operative-video
#19
Kristine Ravina, Ian A Buchanan, Robert C Rennert, Ben A Strickland, Joseph N Carey, Jonathan J Russin
Posterior cerebral artery (PCA) aneurysms can be technically challenging lesions due to the intricacy of perforating branches and the relationship to cranial nerves and the brainstem. Fusiform aneurysms of the perimesencephalic segment of the PCA are a rare finding which does not favor direct clip occlusion or reconstruction. In such cases, proximal parent vessel occlusion is an option for aneurysm treatment. Extracranial-intracranial (EC-IC) bypass can be used to revascularize beyond the lesion when considering proximal occlusion...
April 3, 2018: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/29575325/neural-stem-cell-grafts-promote-astroglia-driven-neurorestoration-in-the-aged-parkinsonian-brain-via-wnt-%C3%AE-catenin-signaling
#20
Francesca L'episcopo, Cataldo Tirolo, Luca Peruzzotti-Jametti, Maria F Serapide, Nunzio Testa, Salvatore Caniglia, Beatrice Balzarotti, Stefano Pluchino, Bianca Marchetti
During aging-one the most potent risk factors for Parkinson's disease (PD)-both astrocytes and microglia undergo functional changes that ultimately hamper homoeostasis, defense, and repair of substantia nigra pars compacta (SNpc) midbrain dopaminergic (mDA) neurons. We tested the possibility of rejuvenating the host microenvironment and boosting SNpc DA neuronal plasticity via the unilateral transplantation of syngeneic neural stem/progenitor cells (NSCs) in the SNpc of aged mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced experimental PD...
March 25, 2018: Stem Cells
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