scholarly journals Distribution of Spinal Sensitization Evoked by Inflammatory Pain Using Local Spinal Cord Glucose Utilization Combined with 3H-Phorbol 12,13-Dibutyrate Binding in Rats

ISRN Pain ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Yasuda Seiko ◽  
Ishikawa Kozo ◽  
Matsumoto Yoshihiro ◽  
Ariyoshi Toru ◽  
Sasaki Hironori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Intracellular Signaling ◽  
Neuronal Excitability ◽  
Tissue Injury ◽  
Mustard Oil ◽  
Functional Changes ◽  
Spinal Cord Regions ◽  
Pdbu Binding

Aims. Hyperalgesia following tissue injury is induced by plasticity in neurotransmission. Few investigators have considered the ascending input which activates the superficial of spinal cord. The aim was to examine neurotransmission and nociceptive processing in the spinal cord after mustard-oil (MO) injection. Both in vitro and in vivo autoradiographs were employed for neuronal activity and transmission in discrete spinal cord regions using the 14C-2-deoxyglucose method and 3H-phorbol 12,13-dibutyrate (3H-PDBu) binding sites. Methods. To quantify the hyperalgesia evoked by MO, the flinching was counted for 60 min after MO (20%, 50 μL) injection in Wistar rats. Simultaneous determination of 14C-2-deoxyglucose and 3H-PDBu binding was used for a direct observation of neuronal/metabolic changes and intracellular signaling in the spinal cord. Results. MO injection evoked an increase in flinching for 60 min. LSCGU significantly increased in the Rexed I-II with 3H-PDBu binding in the ipsilateral side of spinal cord. Discussion. We clearly demonstrated that the hyperalgesia is primarily relevant to increased neuronal activation with PKC activation in the Rexed I-II of the spinal cord. In addition, functional changes such as “neuronal plasticity” may result in increased neuronal excitability and a central sensitization.

Spike Timing-Dependent Plasticity: From Synapse to Perception

2006 ◽  
Vol 86 (3) ◽  
pp. 1033-1048 ◽  
Author(s):  
Yang Dan ◽  
Mu-Ming Poo
Keyword(s):  
Neuronal Excitability ◽  
Human Perception ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Spike Timing Dependent Plasticity ◽  
Dependent Plasticity ◽  
Functional Changes

Information in the nervous system may be carried by both the rate and timing of neuronal spikes. Recent findings of spike timing-dependent plasticity (STDP) have fueled the interest in the potential roles of spike timing in processing and storage of information in neural circuits. Induction of long-term potentiation (LTP) and long-term depression (LTD) in a variety of in vitro and in vivo systems has been shown to depend on the temporal order of pre- and postsynaptic spiking. Spike timing-dependent modification of neuronal excitability and dendritic integration was also observed. Such STDP at the synaptic and cellular level is likely to play important roles in activity-induced functional changes in neuronal receptive fields and human perception.

Moving From an Averaged to Specific View of Spinal Cord Pain Processing Circuits

2007 ◽  
Vol 98 (3) ◽  
pp. 1057-1063 ◽  
Author(s):  
B. A. Graham ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Spinal Cord ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Spinal Pain ◽  
Pain Processing ◽  
In Vivo Animal Models ◽  
Processing Mechanisms ◽  
Made In

Neurons in the superficial dorsal horn (SDH) of the spinal cord play a critical role in processing potentially painful or noxious signals from skin, muscle, and viscera. Many acute pain therapies are based on the notion that altering the excitability of SDH neurons can block or gate these signals and reduce pain. This same notion also underlies treatments for certain chronic pain states. Basic scientists are now beginning to identify a number of potential molecular targets for spinal cord–based pain therapies with a focus on ion channels and receptors that can alter neuronal excitability. The current challenge in pain research is to identify which are the most promising targets and how their manipulation alters pain processing. In this review, we propose that our understanding of spinal pain processing mechanisms and translation of these discoveries into pain therapies could be improved by 1) better appreciating and understanding neuronal heterogeneity in the SDH; 2) establishing connectivity patterns among SDH neuron types; and 3) testing and extending findings made in vitro to intact (in vivo) animal models. As this information becomes available, it will be possible to determine the precise distribution of potential therapeutic targets on various SDH neuron types within specific circuits known to be functionally important in spinal pain processing.

ET-1 induces cortical spreading depression via activation of the ETA receptor/phospholipase C pathway in vivo

2004 ◽  
Vol 286 (4) ◽  
pp. H1339-H1346 ◽  
Author(s):  
Jörg Kleeberg ◽  
Gabor C. Petzold ◽  
Sebastian Major ◽  
Ulrich Dirnagl ◽  
Jens P. Dreier
Keyword(s):  
Receptor Antagonist ◽  
Phospholipase C ◽  
Intracellular Signaling ◽  
Neuronal Excitability ◽  
Calcium Waves ◽  
Direct Stimulation ◽  
Intracellular Signaling Pathway ◽  
Receptor Profile

Recently, it has been shown that brain topical superfusion of endothelin (ET)-1 at concentrations around 100 nM induces repetitive cortical spreading depressions (CSDs) in vivo. It has remained unclear whether this effect of ET-1 is related to a primary neuronal/astroglial effect, such as an increase in neuronal excitability or induction of interastroglial calcium waves, or a penumbra-like condition after vasoconstriction. In vitro, ET-1 regulates interastroglial communication via combined activation of ETA and ETB receptors, whereas it induces vasoconstriction via single activation of ETA receptors. We have determined the ET receptor profile and intracellular signaling pathway of ET-1-induced CSDs in vivo. In contrast to the ETB receptor antagonist BQ-788 and concentration dependently, the ETA receptor antagonist BQ-123 completely blocked the occurrence of ET-1-induced CSDs. The ETB receptor antagonist did not increase the efficacy of the ETA receptor antagonist. Direct stimulation of ETB receptors with the selective ETB agonist BQ-3020 did not trigger CSDs. The phospholipase C (PLC) antagonist U-73122 inhibited CSD occurrence in contrast to the protein kinase C inhibitor Gö-6983. Our findings indicate that ET-1 induces CSDs through ETA receptor and PLC activation. We conclude that the induction of interastroglial calcium waves is unlikely the primary cause of ET-1-induced CSDs. On the basis of the receptor profile, likely primary targets of ET-1 mediating CSD are either neurons or vascular smooth muscle cells.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals The Role of Melatonin on NLRP3 Inflammasome Activation in Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1020
Author(s):  
Burak Ibrahim Arioz ◽  
Emre Tarakcioglu ◽  
Melis Olcum ◽  
Sermin Genc
Keyword(s):  
Nlrp3 Inflammasome ◽  
Intracellular Signaling ◽  
Metabolic Diseases ◽  
Metabolic Stress ◽  
Clinical Importance ◽  
Rapid Identification ◽  
In Vivo Studies ◽  
Inflammasome Activation

NLRP3 inflammasome is a part of the innate immune system and responsible for the rapid identification and eradication of pathogenic microbes, metabolic stress products, reactive oxygen species, and other exogenous agents. NLRP3 inflammasome is overactivated in several neurodegenerative, cardiac, pulmonary, and metabolic diseases. Therefore, suppression of inflammasome activation is of utmost clinical importance. Melatonin is a ubiquitous hormone mainly produced in the pineal gland with circadian rhythm regulatory, antioxidant, and immunomodulatory functions. Melatonin is a natural product and safer than most chemicals to use for medicinal purposes. Many in vitro and in vivo studies have proved that melatonin alleviates NLRP3 inflammasome activity via various intracellular signaling pathways. In this review, the effect of melatonin on the NLRP3 inflammasome in the context of diseases will be discussed.

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

1982 ◽  
Vol 60 (11) ◽  
pp. 1415-1424 ◽  
Author(s):  
H. B. Demopoulos ◽  
E. S. Flamm ◽  
M. L. Seligman ◽  
D. D. Pietronigro ◽  
J. Tomasula ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Free Radical ◽  
Tissue Injury ◽  
Functional Restoration ◽  
Radical Reactions ◽  
Free Radical Reactions ◽  
Cord Injury

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gleb Nikolaevich Zyuz’kov ◽  
Larisa Arkad`evna Miroshnichenko ◽  
Elena Vladislavovna Simanina ◽  
Larisa Alexandrovna Stavrova ◽  
Tatyana Yur`evna Polykova
Keyword(s):  
Stem Cells ◽  
Alcohol Abuse ◽  
Intracellular Signaling ◽  
Signaling Molecules ◽  
Growth Potential ◽  
Nerve Tissue ◽  
Intracellular Signaling Molecules

Abstract Objectives The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo. Methods In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used. Results Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy). Conclusions The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse.

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