Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis

Wang, Junjuan; Wang, Jiaqiu; Lü, Ping; Cai, Youzhi; Hong, Liping; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei

doi:10.1016/j.biomaterials.2015.04.060

Cited by 35 publications

(25 citation statements)

References 34 publications

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“… 233 , 234 Local administration of fingolimod reduces reactive gliosis, prevents neuronal death and improves motor functional recovery after SCI. 235 A 3-day consecutive fingolimod treatment starting at 1 h after TBI significantly reduces as many as 20 kinds of cytokines/chemokines and the infiltrated T and NK cells, but increases the percentage of regulatory T cells, and the concentration of anti-inflammatory IL-10. 236 Fingolimod attenuates the general microglia activation, BBB damage and axonal injury, and improves neurological functions after TBI.…”

Section: Immunotherapy At the Adaptive Immune Response After Cns Injumentioning

confidence: 99%

Potential immunotherapies for traumatic brain and spinal cord injury

Putatunda

Bethea

2018

Chinese Journal of Traumatology

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Traumatic injury of the central nervous system (CNS) including brain and spinal cord remains a leading cause of morbidity and disability in the world. Delineating the mechanisms underlying the secondary and persistent injury versus the primary and transient injury has been drawing extensive attention for study during the past few decades. The sterile neuroinflammation during the secondary phase of injury has been frequently identified substrate underlying CNS injury, but as of now, no conclusive studies have determined whether this is a beneficial or detrimental role in the context of repair. Recent pioneering studies have demonstrated the key roles for the innate and adaptive immune responses in regulating sterile neuroinflammation and CNS repair. Some promising immunotherapeutic strategies have been recently developed for the treatment of CNS injury. This review updates the recent progress on elucidating the roles of the innate and adaptive immune responses in the context of CNS injury, the development and characterization of potential immunotherapeutics, as well as outstanding questions in this field.

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Section: Immunotherapy At the Adaptive Immune Response After Cns Injumentioning

confidence: 99%

Potential immunotherapies for traumatic brain and spinal cord injury

Putatunda

Bethea

2018

Chinese Journal of Traumatology

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“…S1P receptors are widely expressed in the nervous system, with S1P 1 presumably being the most predominant subtype. Adult mouse sensory neurons express the S1P receptor subtypes S1P 1 , S1P 2 and S1P 3 (Mair et al, 2011 ; Wang et al, 2015 ): S1P 1 receptors are expressed in the nociceptor population, S1P 2 receptors in the proprioceptive neurons and S1P 3 receptors are present virtually in all neurons in the DRG (Mair et al, 2011 ; Camprubí-Robles et al, 2013 ). S1P 1 activation controls cytoskeletal rearrangements and cell motility and enhances cortical actin formation (Rosenfeldt et al, 2001a , b ).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation

Quarta

Camprubí-Robles

Schweigreiter

et al. 2017

Front. Mol. Neurosci.

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The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation. The S1P1 receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was S1P-induced neurite retraction mitigated in S1P1-deficient neurons. Depletion of S1P3 receptors however resulted in a dramatic inhibition of S1P-induced neurite retraction and was on the contrary associated with a significant elongation of neuronal processes in response to S1P. Opposing responses to S1P could be observed in the same neuron population, where S1P could activate S1P1 receptors to stimulate elongation or S1P3 receptors and retraction. S1P was, for the first time in sensory neurons, linked to the phosphorylation of collapsin response-mediated protein-2 (CRMP2), which was inhibited by ROCK inhibition. The improved sensory recovery after crush injury further supported the relevance of a critical role for S1P and receptors in fine-tuning axonal outgrowth in peripheral neurons.

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“…These are the indirect controls account for biological events such as induction of iNOS, release of NO, MCP-1 and CINCS. (Kesanakurti et al, 2009, Lindemann, Marschall, 2015) It is likely in the future, that nutraceuticals could be utilized to both attenuate risk of CNS inflammatory processes and age-related cognitive decline (Wang et al, 2015a) as well as survival, migration and invasion of glioblastomas (Lamy et al, 2015, Leidgens et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Mazzio

Bauer

Mendonca

et al. 2017

Journal of Neuroimmunology

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Chronic or acute central nervous system (CNS) inflammation is carried out by glial cells, which can contribute to neurological injuries associated with head trauma, stroke, and infection, Parkinson’s or Alzheimer ’s disease. The process of aging combined with inflammation are also risk factors for developing glioblastoma multiforme (GBM) as well as perpetuating its malignant aggression. With growing public curiosity in complementary and alternative medicines (CAMs), in this work we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells. Validation studies suggest a pro-inflammatory profile mediated by LPS [3μg/ml/IFNγ 3ng/ml] is consistent with elevation [> 8.5 fold] of MCP-1 and cytokine-induced neutrophil chemo-attractants (CINC) 1, CINC 2a and CINC3. The data show no evidence of changes to the following, IL-13, TNF-a, fracktaline, leptin, LIX, GM-CSF, ICAM1, L-Selectin, activin A, agrin, IL-1α, MIP-3a, B72/CD86, NGF, IL-1b, MMP-8, IL-1 R6, PDGF-AA, IL-2, IL-4, prolactin R, RAGE, IL-6, Thymus Chemokine-1, CNTF,IL-10 or TIMP-1. The data also show a LPS/IFNγ mediated rise in iNOS and NO2− as often reported. A HTP screening was conducted, where we employ an in vitro efficacy index (iEI) defined as the ratio of toxicity (LC50)/anti-inflammatory potency (IC50) to ensure biological effects were occurring in fully viable cells (ratio > 3.8). Using NO2− as a guideline molecule, the data show that 1.77 % (25 of 1410 tested) (at <250μg/ml) had anti-inflammatory effects with an iEI ratio >3.8. These include reference drugs (hydrocortisone, dexamethasone N6-(1-iminoethyl)-L-lysine and NSAIDS : diclofenac, tolfenamic acid), a histone deacetylase inhibitor (apicidin) and the following natural products; Ashwaganda (Withania somnifera), Elecampagne Root (Inula helenium), Feverfew (Tanacetum parthenium), Green Tea (Camellia sinensis), Turmeric Root (Curcuma Longa) Ganthoda (Valeriana wallichii), Tansy (Tanacetum vulgare), Maddar Root (Rubia tinctoria), Red Sandle wood (Pterocarpus santalinus), Bay Leaf (Laurus nobilis, Lauraceae), quercetin, cardamonin, fisetin, EGCG, biochanin A, galangin, apigenin and curcumin. The herb with the largest iEI was Ashwaganda where the IC50/LC50 was 11.1/>1750.0 μg/mL, and the compound with the greatest iEI was quercetin where the IC50/LC50 was 10.0/>363.6 ug/mL. These substances also downregulate the production of iNOS expression and attenuate CINC-3 release. In summary, this HTP screening provides guideline information as to efficacy of natural products that in the long term, could prevent inflammatory processes associated with neurodegenerative disease and aggressive glioma tumor growth.

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Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis

Cited by 35 publications

References 34 publications

Potential immunotherapies for traumatic brain and spinal cord injury

Potential immunotherapies for traumatic brain and spinal cord injury

Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

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