scholarly journals TSPO Expression Modulatory Effect of Acetylcholinesterase Inhibitor in the Ischemic Stroke Rat Model

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1350
Author(s):  
Yoo Sung Song ◽  
Sang Hee Lee ◽  
Jae Ho Jung ◽  
In Ho Song ◽  
Hyun Soo Park ◽  
...  
Keyword(s):  
Rat Model ◽  
Ache Activity ◽  
Inflammatory Responses ◽  
Acetylcholinesterase Inhibitor ◽  
Contralateral Side ◽  
Translocator Protein ◽  
Ache Inhibitor ◽  
Sprague Dawley ◽  
Brain Response

We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

scholarly journals The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats

2020 ◽  
Vol 21 (2) ◽  
pp. 413
Author(s):  
Jihae Park ◽  
Jee Taek Kim ◽  
Soo Jin Lee ◽  
Jae Chan Kim
Keyword(s):  
Western Blot ◽  
Inflammatory Cytokines ◽  
Aqueous Humor ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Ocular Tissue ◽  
Tnf Α ◽  
Anti Inflammatory

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

2004 ◽  
Vol 287 (3) ◽  
pp. H1286-H1295 ◽  
Author(s):  
Sarah J. Canyon ◽  
Geoffrey P. Dobson
Keyword(s):  
Infarct Size ◽  
Rat Model ◽  
Cardiac Death ◽  
Constant Infusion ◽  
Therapeutic Window ◽  
High Dose ◽  
Sprague Dawley ◽  
Myocardial Ischemia And Reperfusion ◽  
Regional Ischemia

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), ventricular tachycardia (VT), or cardiac ischemia that show a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common antiarrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats ( n = 49) were anesthetized with pentobarbital sodium (60 mg·ml−1·kg−1 ip) and instrumented for regional coronary occlusion (30 min) and reperfusion (120 min). Heart rate, blood pressure, and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 min before ischemia and extended throughout ischemia, terminating at the start of reperfusion. After 120 min, hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls ( n = 12), 50% of adenosine only (305 μg·kg−1·min−1, n = 8), 0% in lidocaine only (608 μg·kg−1·min−1, n = 8), and 0% in AL at any dose (152, 305, or 407 μg·kg−1·min−1 adenosine plus 608 μg·kg−1·min−1 lidocaine, n = 7, 8, and 6). VT occurred in 100% of saline controls (18 ± 9 episodes), 50% of adenosine-only (11 ± 7 episodes), 83% of lidocaine-only (23 ± 11 episodes), 60% of low-dose AL (2 ± 1 episodes, P < 0.05), 57% of mid-dose AL (2 ± 1 episodes, P < 0.05), and 67% of high-dose AL rats (6 ± 3 episodes). VF occurred in 75% of saline controls (4 ± 3 episodes), 100% of adenosine-only-treated rats (3 ± 2 episodes), and 33% lidocaine-only-treated rats (2 ± 1 episodes) of the rats tested. There was no deaths and no VF in the low- and mid-dose AL-treated rats during ischemia, and only one high-dose AL-treated rat experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats but only reached significance with the mid-dose treatment (saline controls 61 ± 5% vs. 38 ± 6%, P < 0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window in ischemic and nonischemic regions of the heart.

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

Electroacupuncture ameliorates corticotrophin-releasing factor-induced jejunal dysmotility in a rat model of stress

2020 ◽  
pp. 096452842092028
Author(s):  
Yu-Xue Zhao ◽  
Chang-Xiang Cui ◽  
Jun-Hong Gao ◽  
Jun Liu ◽  
Qun Liu ◽  
...  
Keyword(s):  
Rat Model ◽  
Gastrointestinal Transit ◽  
Receptor Subtype ◽  
Motor Disorder ◽  
Sprague Dawley ◽  
Functional Roles ◽  
Corticotrophin Releasing Factor ◽  
Sprague Dawley Rats ◽  
Gi Motility

Background Central injection of corticotrophin-releasing factor (CRF) mimics the effect of stress on gastrointestinal (GI) responses, including inhibition of GI motility. This study was designed to explore the effects of electroacupuncture (EA) on disordered jejunal motility in a rat model of stress induced by intracisternal (IC) injection of CRF. Methods A stress model was established by IC injection of CRF in Sprague–Dawley rats. GI motility was evaluated by assessing gastric emptying (GE), gastrointestinal transit (GIT) and jejunal motility in vivo. EA was performed at ST36. The functional roles of CRF receptor subtype 1 and subtype 2 (CRFr1 and CRFr2) were examined by IC administration of the corresponding selective CRF antagonists. Protein expression of CRFr1 and CRFr2 in the hypothalamus and jejunum was detected by Western blotting. Results IC injection of CRF significantly inhibited GE, GIT and jejunal motility. EA treatment remarkably improved the disturbed GI motility. Intriguingly, the disordered jejunal motility induced by central CRF was abolished by IC injection of a selective CRFr2 antagonist, indicating the essential role of central CRFr2 in mediating the stress-induced jejunal motor disorder. EA at ST36 decreased central and peripheral expression of CRFr2, which might be one of the potential mechanisms underlying the beneficial effect of EA on jejunal dysmotility in this rat model of stress. Conclusion This study suggested that EA at ST36 could ameliorate disordered jejunal motility induced by stress, and that this might be associated with the down-regulation of CRFr2.

scholarly journals Males and females exhibit distinct relationships between intervertebral disc degeneration and pain in a rat model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Grace E. Mosley ◽  
Minghui Wang ◽  
Philip Nasser ◽  
Alon Lai ◽  
Daniel A. Charen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Network Analysis ◽  
Intervertebral Disc ◽  
Rat Model ◽  
Biomechanical Testing ◽  
Sprague Dawley ◽  
Discogenic Pain ◽  
Males And Females ◽  
Ivd Degeneration

Abstract Back pain is linked to intervertebral disc (IVD) degeneration, but clinical studies show the relationship is complex. This study assessed whether males and females have distinct relationships between IVD degeneration and pain using an in vivo rat model. Forty-eight male and female Sprague–Dawley rats had lumbar IVD puncture or sham surgery. Six weeks after surgery, IVDs were evaluated by radiologic IVD height, histological grading, and biomechanical testing. Pain was assessed by von Frey assay and dorsal root ganglia (DRG) expression of Calca and Tac1 genes. Network analysis visualized which measures of IVD degeneration most related to pain by sex. In both females and males, annular puncture induced structural IVD degeneration, but functional biomechanical properties were similar to sham. Females and males had distinct differences in mechanical allodynia and DRG gene expression, even though sex differences in IVD measurements were limited. Network analysis also differed by sex, with more associations between annular puncture injury and pain in the male network. Sex differences exist in the interactions between IVD degeneration and pain. Limited correlation between measures of pain and IVD degeneration highlights the need to evaluate pain or nociception in IVD degeneration models to better understand nervous system involvement in discogenic pain.

Abstract 226: Recellularization of Xenograft Heart Valves Reduces the Xenoreactive Immune Response in an In Vivo Rat Model

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Sabin J Bozso ◽  
Ryaan EL-Andari ◽  
Lin Fu Zhu ◽  
Benjamin Adam ◽  
Michael C Moon ◽  
...  
Keyword(s):  
Immune Response ◽  
Aortic Valve ◽  
Guinea Pig ◽  
Rat Model ◽  
Serum Immunoglobulin ◽  
Total Serum ◽  
Sprague Dawley ◽  
Cellular Infiltrate ◽  
Immunoglobulin Production

Background: Current xenograft valve constructs provoke an intense immune response that may lead to valve dysfunction. Our aim was to address the role of autologous mesenchymal stem cell (MSC) recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in-vivo rat model. Methods: Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with syngeneic Sprague-Dawley rat MSCs. The recellularized aortic valve xenografts were then implanted into the infrarenal aorta of recipient female Sprague-Dawley rats. Grafts were implanted as either syngeneic grafts, non-decellularized (fresh), decellularized and recellularized xenografts. Rats were euthanized after 7-days, exsanguinated and the grafts explanted. Total serum immunoglobulin was quantified and histological analysis perfomed to analyze the immune response. Results: Overall survival to endpoint was significantly lower in the decellularized xenograft group (67%; 4/6), compared to fresh (100%; 6/6) and recellularized grafts (100%; 6/6). Similarly grafts in the decellularized group were more likely to have completely thrombosed (50%; 2/4), compared to fresh (33%; 2/6) and recellularized grafts (0%; 0/6). Decellularized guinea pig xenografts, when implanted into rats in-vivo , result in significantly reduced total serum immunoglobulin production and significantly reduced graft cellular infiltrate when compared to fresh xenografts. Moreover, when decellularized guinea pig xenografts were recellularized with syngeneic rat MSCs there was an additional decrease in total serum immunoglobulin production and graft cellular infiltrate when compared to both fresh and decellularized xenografts. Importantly, recellularized guinea pig xenografts had an equivalent total immunoglobulin production and graft cellular infiltrate when compared to syngeneic rat aortic valve controls. Conclusions: Autologous MSC recellularization of xenogenic valves reduces the xenoreactive immune response in an in-vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.

scholarly journals The Effect of Sertoli Cells on Xenotransplantation and Allotransplantation of Ventral Mesencephalic Tissue in a Rat Model of Parkinson’s Disease

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1420
Author(s):  
Yun-Ting Jhao ◽  
Chuang-Hsin Chiu ◽  
Chien-Fu F. Chen ◽  
Ta-Kai Chou ◽  
Yi-Wen Lin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Sertoli Cells ◽  
Dopaminergic Neurons ◽  
Sprague Dawley ◽  
Drug Induced ◽  
In Vivo Evaluation ◽  
Ventral Mesencephalic

Intra-striatal transplantation of fetal ventral mesencephalic (VM) tissue has a therapeutic effect on patients with Parkinson’s disease (PD). Sertoli cells (SCs) possess immune-modulatory properties that benefit transplantation. We hypothesized that co-graft of SCs with VM tissue can attenuate rejection. Hemi-parkinsonian rats were generated by injecting 6-hydroxydopamine into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats or pigs (rVM or pVM), with/without a co-graft of SCs (rVM+SCs or pVM+SCs). Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small animal-positron emission tomography (PET) coupled with [18F] DOPA or [18F] FE-PE2I, respectively. Immunohistochemistry (IHC) examination was used to determine the survival of the grafted dopaminergic neurons in the striatum and to investigate immune-modulatory effects of SCs. The results showed that the rVM+SCs and pVM+SCs groups had significantly improved drug-induced rotational behavior compared with the VM alone groups. PET revealed a significant increase in specific uptake ratios (SURs) of [18F] DOPA and [18F] FE-PE2I in the grafted striatum of the rVM+SCs and pVM+SCs groups as compared to that of the rVM and pVM groups. SC and VM tissue co-graft led to better dopaminergic (DA) cell survival. The co-grafted groups exhibited lower populations of T-cells and activated microglia compared to the groups without SCs. Our results suggest that co-graft of SCs benefit both xeno- and allo-transplantation of VM tissue in a PD rat model. Use of SCs enhanced the survival of the grafted dopaminergic neurons and improved functional recovery. The enhancement may in part be attributable to the immune-modulatory properties of SCs. In addition, [18F]DOPA and [18F]FE-PE2I coupled with PET may provide a feasible method for in vivo evaluation of the functional integrity of the grafted DA cell in parkinsonian rats.

scholarly journals Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson’s disease

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Yi Wu ◽  
Yang-Yi Chen ◽  
Jia-Jia Lin ◽  
Jui-Ping Li ◽  
Jen-Kun Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Right Hemisphere ◽  
Copper Catalyst ◽  
Radiochemical Yield ◽  
Translocator Protein ◽  
Secondary Brain Injury ◽  
Sprague Dawley ◽  
The Brain

Abstract Purpose The inflammation reaction in the brain may stimulate damage repair or possibly lead to secondary brain injury. It is often associated with activated microglia, which would overexpress 18-kDa translocator protein (TSPO). In this study, we successfully developed a new TSPO radioligand, [18F]-2-(4-fluoro-2-(p-tolyloxy)phenyl)-1,2-dihydroisoquinolin-3(4H)-one ([18F]FTPQ), and evaluate its potential to noninvasively detect brain changes in a rat model of Parkinson’s disease (PD). Procedures The precursor (8) for [18F]FTPQ preparation was synthesized via six steps. Radiofluorination was carried out in the presence of a copper catalyst, and the crude product was purified by high-performance liquid chromatography (HPLC) to give the desired [18F]FTPQ. The rat model of PD was established by the injection of 6-OHDA into the right hemisphere of male 8-week-old Sprague-Dawley rats. MicroPET/CT imaging and immunohistochemistry (IHC) were performed to characterize the biological properties of [18F]FTPQ. Results The overall chemical yield for the precursor (8) was around 14% after multi-step synthesis. The radiofluorination efficiency of [18F]FTPQ was 60 ± 5%. After HPLC purification, the radiochemical purity was higher than 98%. The overall radiochemical yield was approximately 19%. The microPET/CT images demonstrated apparent striatum accumulation in the brains of PD rats at the first 30 min after intravenous injection of [18F]FTPQ. Besides, longitudinal imaging found the uptake of [18F]FTPQ in the brain may reflect the severity of PD. The radioactivity accumulated in the ipsilateral hemisphere of PD rats at 1, 2, and 3 weeks after 6-OHDA administration was 1.84 ± 0.26, 3.43 ± 0.45, and 5.58 ± 0.72%ID/mL, respectively. IHC revealed that an accumulation of microglia/macrophages and astrocytes in the 6-OHDA-injected hemisphere. Conclusions In this study, we have successfully synthesized [18F]FTPQ with acceptable radiochemical yield and demonstrated the feasibility of [18F]FTPQ as a TSPO radioligand for the noninvasive monitoring the disease progression of PD.

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