Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Neuroprotective Strategies 2015

Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 December 2015) | Viewed by 78418

Share This Special Issue

Special Issue Editor

Prof. Dr. Katalin Prokai-Tatrai

E-Mail Website
Guest Editor

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
Interests: drug design of central nervous system agents; neuropeptides and peptidomimetics; prodrugs for CNS delivery; CNS-selective estrogen therapy; neuroprotection; proteomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We started the “Neuroprotective Strategies” collection jointly with Molecules in 2009. It was a great success; a large number of reviews and original research articles were published in the inaugural volume. Since then, the International Journal of Molecular Sciences has successfully continued this collection covering neuroprotection broadly including, but not limited to, preclinical/basic science assessments of various animal models relevant to diseases and agents with potential or perceived translation values. We open up the “Neuroprotective Strategies” Topical Collection to thought-provoking Comments, Opinions and Perspectives, in addition to our traditional Reviews and Research Articles in this field. We especially encourage submissions that address critical issues having prevented successful clinical translations of promising laboratory data. Limitations of in vitro studies and preclinical animal models to mirror multiple pathologies underlying human neurodegenerative diseases, lack of drug-likeness of experimental agents, the need to consider absorption, distribution, metabolism, elimination, toxicology (ADMET) and pharmacokinetics even in the early stage of drug discovery, as well as obstacles of drug delivery to the CNS are only some of the issues that come to mind regard this matter. Critical reviews on relevant patent literature are also welcome. I give thanks for past contributions and look forward to receiving future contributions on the promising and challenging aspects of the field. The following links: https://www.mdpi.com/journal/ijms/special_issues/Neuroprotective_strategies_collection and https://www.mdpi.com/journal/molecules/special_issues/neuroprotec-strateg point to already published papers within this special issue.

Dr. Katalin Prokai-Tatrai
Collection Editor

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. The article processing charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs).

Keywords

aging
CNS drug design and delivery
CNS injury
inflammation
in vitro and in vivo models of neurodegeneration
ischemia
neurodegenerative diseases
oxidative stress
peripheral nerve injury
stroke
stem cells
structure-activity relationship
translational medicine

Related Special Issue

Neuroprotective Strategies 2022 in International Journal of Molecular Sciences (183 articles)

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review, Other

6955 KiB

Open AccessArticle

by Shuang Hu, Di Wang, Junrong Zhang, Mengyan Du, Yingkun Cheng, Yan Liu, Ning Zhang, Di Wang and Yi Wu

Int. J. Mol. Sci. 2016, 17(2), 133; https://doi.org/10.3390/ijms17020133 - 26 Jan 2016

Cited by 38 | Viewed by 6406

Abstract

The present study aims to explore the neuro-protective effects of purified Sparassis crispa polysaccharides against l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cell damages and its underlying mechanisms. The Sparassis crispa water extract was purified by a DEAE-52 cellulose anion exchange column and a Sepharose G-100 column. A fraction with a molecular weight of 75 kDa and a diameter of 88.9 nm, entitled SCWEA, was obtained. SCWEA was identified with a triple helix with (1→3)-linked Rha in the backbone, and (1→2) linkages and (1→6) linkages in the side bone. Our results indicated that the pre-treatment of DPC12 cells with SCWEA prior to l-Glu exposure effectively reversed the reduction on cell viability (by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay) and reduced l-Glu-induced apoptosis (by Hoechst staining). SCWEA decreased the accumulation of intracellular reactive oxygen species, blocked Ca²⁺ influx and prevented depolarization of the mitochondrial membrane potential in DPC12 cells. Furthermore, SCWEA normalized expression of anti-apoptotic proteins in l-Glu-explored DPC12 cells. These results suggested that SCWEA protects against l-Glu-induced neuronal apoptosis in DPC12 cells and may be a promising candidate for treatment against neurodegenerative disease. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Figure 1

3037 KiB

Open AccessArticle

Genipin Derivatives Protect RGC-5 from Sodium Nitroprusside-Induced Nitrosative Stress

by Rikang Wang, Jiaqiang Zhao, Lei Zhang, Lizhi Peng, Xinyi Zhang, Wenhua Zheng and Heru Chen

Int. J. Mol. Sci. 2016, 17(1), 117; https://doi.org/10.3390/ijms17010117 - 19 Jan 2016

Cited by 5 | Viewed by 5182

Abstract

CHR20 and CHR21 are a pair of stable diastereoisomers derived from genipin. These stereoisomers are activators of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). In the rat retinal ganglion (RGC-5) cell model these compounds are non-toxic. Treatment of RGC-5 with 750 μM of sodium nitroprusside (SNP) produces nitrosative stress. Both genipin derivatives, however, protect these cells against SNP-induced apoptic cell death, although CHR21 is significantly more potent than CHR20 in this regard. With Western blotting we showed that the observed neuroprotection is primarily due to the activation of protein kinase B (Akt)/eNOS and extracellular signal-regulated kinase (ERK1/2) signaling pathways. Therefore, LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor) or PD98059 (a MAPK-activating enzyme inhibitor) abrogated the protective effects of CHR20 and CHR21. Altogether, our results show that in our experimental setup neuroprotection by the diasteromeric pair is mediated through the PI3K/Akt/eNOS and ERK1/2 signaling pathways. Further studies are needed to establish the potential of these compounds to prevent ntric oxide (NO)-induced toxicity commonly seen in many neurodegenerative diseases. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Graphical abstract

2172 KiB

Open AccessArticle

In Vitro and in Vivo Neuroprotective Effects of Walnut (Juglandis Semen) in Models of Parkinson’s Disease

by Jin Gyu Choi, Gunhyuk Park, Hyo Geun Kim, Dal-Seok Oh, Hocheol Kim and Myung Sook Oh

Int. J. Mol. Sci. 2016, 17(1), 108; https://doi.org/10.3390/ijms17010108 - 15 Jan 2016

Cited by 25 | Viewed by 6794

Abstract

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines including dopamine (DA). MAO expression is elevated in Parkinson’s disease (PD). An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B)) participates in the generation of reactive oxygen species (ROS), such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen) has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP⁺)- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP⁺ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Graphical abstract

2388 KiB

Open AccessArticle

The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

by Lucia Machova Urdzikova, Kristyna Karova, Jiri Ruzicka, Anna Kloudova, Craig Shannon, Jana Dubisova, Raj Murali, Sarka Kubinova, Eva Sykova, Meena Jhanwar-Uniyal and Pavla Jendelova

Int. J. Mol. Sci. 2016, 17(1), 49; https://doi.org/10.3390/ijms17010049 - 31 Dec 2015

Cited by 48 | Viewed by 6922

Abstract

Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Graphical abstract

3199 KiB

Open AccessArticle

Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

by Yan Zhu, Xiao Chen, Zhan Liu, Yu-Ping Peng and Yi-Hua Qiu

Int. J. Mol. Sci. 2016, 17(1), 25; https://doi.org/10.3390/ijms17010025 - 28 Dec 2015

Cited by 42 | Viewed by 6233

Abstract

Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson’s disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Figure 1

14316 KiB

Open AccessArticle

Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment

by Fu-Xing Zuo, Xin-Jie Bao, Xi-Cai Sun, Jun Wu, Qing-Ran Bai, Guo Chen, Xue-Yuan Li, Qiang-Yi Zhou, Yuan-Fan Yang, Qin Shen and Ren-Zhi Wang

Int. J. Mol. Sci. 2015, 16(11), 26473-26492; https://doi.org/10.3390/ijms161125966 - 05 Nov 2015

Cited by 36 | Viewed by 7400

Abstract

Parkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Graphical abstract

3642 KiB

Open AccessArticle

Roles of Sestrin2 and Ribosomal Protein S6 in Transient Global Ischemia-Induced Hippocampal Neuronal Injury

by Yao-Chung Chuang, Jenq-Lin Yang, Ding-I Yang, Tsu-Kung Lin, Chia-Wei Liou and Shang-Der Chen

Int. J. Mol. Sci. 2015, 16(11), 26406-26416; https://doi.org/10.3390/ijms161125963 - 04 Nov 2015

Cited by 32 | Viewed by 6407

Abstract

Recent studies suggested that sestrin2 is a crucial modulator for the production of reactive oxygen species (ROS). In addition, sestrin2 may also regulate ribosomal protein S6 (RpS6), a molecule important for protein synthesis, through the effect of mammalian target of rapamycin (mTOR) complex that is pivotal for longevity. However, the roles of sestrin2 in cerebral ischemia, in which oxidative stress is one of the major pathogenic mechanisms, are still less understood. In this study, we hypothesized that sestrin2 may protect hippocampal CA1 neurons against transient global ischemia (TGI)-induced apoptosis by regulating RpS6 phosphorylation in rats. We found that sestrin2 expression was progressively increased in the hippocampal CA1 subfield 1–48 h after TGI, reaching the maximal level at 24 h, and declined thereafter. Further, an increased extent of RpS6 phosphorylation, but not total RpS6 protein level, was observed in the hippocampal CA1 subfield after TGI. The sestrin2 siRNA, which substantially blocked the expression of TGI-induced sestrin2, also abolished RpS6 phosphorylation. TGI with reperfusion may induce oxidative stress with the resultant formation of 8-hydroxy-deoxyguanosine (8-OHdG). We found that sestrin2 siRNA further augmented the formation of 8-OHdG induced by TGI with reperfusion for 4 h. Consistently, sestrin2 siRNA also enhanced apoptosis induced by TGI with reperfusion for 48 h based on the analysis of DNA fragmentation by agarose gel electrophoresis, DNA fragmentation sandwich ELISA, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Together these findings indicated that TGI-induced sestrin2 expression contributed to RpS6 phosphorylation and neuroprotection against ischemic injury in the hippocampal CA1 subfield. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Figure 1

Review

Jump to: Research, Other

1207 KiB

Open AccessReview

Retinal Cell Degeneration in Animal Models

by Masayuki Niwa, Hitomi Aoki, Akihiro Hirata, Hiroyuki Tomita, Paul G. Green and Akira Hara

Int. J. Mol. Sci. 2016, 17(1), 110; https://doi.org/10.3390/ijms17010110 - 15 Jan 2016

Cited by 42 | Viewed by 7162

Abstract

The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl₂-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Graphical abstract

1493 KiB

Open AccessReview

The Importance of Thrombin in Cerebral Injury and Disease

by Harald Krenzlin, Viola Lorenz, Sven Danckwardt, Oliver Kempski and Beat Alessandri

Int. J. Mol. Sci. 2016, 17(1), 84; https://doi.org/10.3390/ijms17010084 - 11 Jan 2016

Cited by 90 | Viewed by 8240

Abstract

There is increasing evidence that prothrombin and its active derivative thrombin are expressed locally in the central nervous system. So far, little is known about the physiological and pathophysiological functions exerted by thrombin in the human brain. Extra-hepatic prothrombin expression has been identified in neuronal cells and astrocytes via mRNA measurement. The actual amount of brain derived prothrombin is expected to be 1% or less compared to that in the liver. The role in brain injury depends upon its concentration, as higher amounts cause neuroinflammation and apoptosis, while lower concentrations might even be cytoprotective. Its involvement in numerous diseases like Alzheimer’s, multiple sclerosis, cerebral ischemia and haemorrhage is becoming increasingly clear. This review focuses on elucidation of the cerebral thrombin expression, local generation and its role in injury and disease of the central nervous system. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Graphical abstract

1139 KiB

Open AccessReview

Changing the Face of Kynurenines and Neurotoxicity: Therapeutic Considerations

by Zsuzsanna Bohár, József Toldi, Ferenc Fülöp and László Vécsei

Int. J. Mol. Sci. 2015, 16(5), 9772-9793; https://doi.org/10.3390/ijms16059772 - 29 Apr 2015

Cited by 59 | Viewed by 8931

Abstract

Kynurenines are the products of tryptophan metabolism. Among them, kynurenine and kynurenic acid are generally thought to have neuroprotective properties, while 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid are considered neurotoxic. They participate in immunoregulation and inflammation and possess pro- or anti-excitotoxic properties, and their involvement in oxidative stress has also been suggested. Consequently, it is not surprising that kynurenines have been closely related to neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. More information about the less-known metabolites, picolinic and cinnabarinic acid, evaluation of new receptorial targets, such as aryl-hydrocarbon receptors, and intensive research on the field of the immunomodulatory function of kynurenines delineated the high importance of this pathway in general homeostasis. Emerging knowledge about the kynurenine pathway provides new target points for the development of therapeutical solutions against neurodegenerative diseases. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Figure 1

Other

Jump to: Research, Review

2011 KiB

Open AccessCase Report

Brain Recovery after a Plane Crash: Treatment with Growth Hormone (GH) and Neurorehabilitation: A Case Report

by Jesús Devesa, Gustavo Díaz-Getino, Pablo Rey, José García-Cancela, Iria Loures, Sonia Nogueiras, Alba Hurtado de Mendoza, Lucía Salgado, Mónica González, Tamara Pablos and Pablo Devesa

Int. J. Mol. Sci. 2015, 16(12), 30470-30482; https://doi.org/10.3390/ijms161226244 - 21 Dec 2015

Cited by 30 | Viewed by 7822

Abstract

The aim of this study is to describe the results obtained after growth hormone (GH) treatment and neurorehabilitation in a young man that suffered a very grave traumatic brain injury (TBI) after a plane crash. Methods: Fifteen months after the accident, the patient was treated with GH, 1 mg/day, at three-month intervals, followed by one-month resting, together with daily neurorehabilitation. Blood analysis at admission showed that no pituitary deficits existed. At admission, the patient presented: spastic tetraplegia, dysarthria, dysphagia, very severe cognitive deficits and joint deformities. Computerized tomography scanners (CT-Scans) revealed the practical loss of the right brain hemisphere and important injuries in the left one. Clinical and blood analysis assessments were performed every three months for three years. Feet surgery was needed because of irreducible equinovarus. Results: Clinical and kinesitherapy assessments revealed a prompt improvement in cognitive functions, dysarthria and dysphagia disappeared and three years later the patient was able to live a practically normal life, walking alone and coming back to his studies. No adverse effects were observed during and after GH administration. Conclusions: These results, together with previous results from our group, indicate that GH treatment is safe and effective for helping neurorehabilitation in TBI patients, once the acute phase is resolved, regardless of whether or not they have GH-deficiency (GHD). Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2015)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Neuroprotective Strategies 2015

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI