scholarly journals Effects of PS-519 combined with thrombolytic therapy in embolic stroke in rat

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 351-351
Author(s):  
Li Zhang ◽  
Zheng G Zhang ◽  
Michael Chopp ◽  
Peter J Elliott ◽  
Julian Adams
Keyword(s):  
Combination Treatment ◽  
Cell Damage ◽  
Infarct Volume ◽  
Body Weight Loss ◽  
Embolic Stroke ◽  
Therapeutic Window ◽  
Control Group ◽  
Lesion Volume ◽  
Treatment Groups ◽  
Mca Occlusion

P67 We evaluated the effect of a proteasome inhibitor (PS-519) which blocks the activation of NF-kB, alone or combination with thrombolysis, on ischemic cell damage after embolic stroke in rat. Male Wistar rats (n=44) were subjected to embolic middle cerebral artery (MCA) occlusion. Animals were randomly assigned into seven groups: PS-519 treatment groups (n=6 each group) were infused intravenously with PS-519(1.0 mg/kg) at 2 h, 4 h, or 6 h after MCA occlusion, respectively. Combination treatment groups (n=6 each group) PS-519(1.0 mg/kg) followed by rtPA (10 mg/kg) were administered at 2 h, 4 h, or 6 h after MCA occlusion. A control group (n=8) was administered saline at 2 h after MCA occlusion. Rats were sacrificed 7 days after MCA occlusion, infarct volume and gross hemorrhage were measured. In PS-519 treatment groups: infarct volume was significantly (p<0.05) reduced by PS-519 treatment at 2 (19”3.5%) and 4 h (22“3.1%) after MCA occlusion when compared with the control group (34”3.5%). However, no significant reduction of lesion volume was found in the 6 hour treated group (34“2.5%). In the combination treatment groups: infarction volume was significantly (p<0.05) reduced in all three groups compared with control: 2 h (18”4.3%), 4 h (21“3.6%), 6 h (21”4.4%). None of treated rats and 25% of control rats had intracerebral gross hemorrhage. Significant reductions (p<0.05) in neurological deficit and body weight loss were found in all treated groups except the group that treated with PS-519 alone at 6 h. Our results demonstrate that administration of PS-519 alone, or combination with rtPA significantly reduces ischemic cell damage. Moreover, combination treatment with PS-519 and rtPA expands the therapeutic window to at least 6 h after embolic stroke. This suggests that combination therapy might lead to improved neurological outcome beyond that which would occur with neuroprotective treatment or thrombolytics alone.

scholarly journals Analysis of Combined Treatment of Embolic Stroke in Rat with r-tPA and a GPIIb/IIIa Inhibitor

2005 ◽  
Vol 25 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Guangliang Ding ◽  
Quan Jiang ◽  
Li Zhang ◽  
Zheng Gang Zhang ◽  
Lian Li ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Thrombolytic Therapy ◽  
Combination Treatment ◽  
Infarct Volume ◽  
Embolic Stroke ◽  
Control Group ◽  
Resonance Imaging ◽  
Cerebral Microvessels ◽  
Magnetic Resonance Imaging Mri

Suppression of platelet activation improves the efficacy of thrombolytic therapy for stroke. Thus, combination treatment with recombinant tissue plasminogen activator (r-tPA) and 7E3 F(ab′)2, a GPIIb/IIIa inhibitor that binds the platelet to fibrin, may improve the efficacy of thrombolytic therapy in embolic stroke. Magnetic resonance imaging (MRI) was used to monitor treatment response in rats subjected to embolic middle cerebral artery (MCA) occlusion (MCAo). Animals were randomized into treated ( n = 12) and control ( n = 10) groups and received intravenous combination therapy or saline, respectively, 4 hours after MCAo. Magnetic resonance imaging (MRI) measurements performed 1 hour after MCAo showed no difference between groups. However, an increased incidence (50%) of MCA recanalization was found in the treated group at 24 hours compared with 20% in the control group. The area of low cerebral blood flow at 24 and 48 hours was significantly smaller in the combination treatment group, and the lesion size, as indicated from the T2 and T1 maps, differed significantly between groups. Fluorescence microscopy measurements of cerebral microvessels perfused with fluorescein isothiocyanate-dextran and measurements of infarct volume revealed that the combination treatment significantly increased microvascular patency and reduced infarct volume, respectively, compared with the control rats. The efficacy of combination treatment 4 hours after ischemia is reflected by MRI indices of tissue perfusion, MCA recanalization, and reduction of lesion volume. The treatment also reduced secondary microvascular perfusion deficits.

scholarly journals Atorvastatin Extends the Therapeutic Window for tPA to 6 h after the Onset of Embolic Stroke in Rats

2009 ◽  
Vol 29 (11) ◽  
pp. 1816-1824 ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Longfei Jia ◽  
Yisheng Cui ◽  
Mei Lu ◽  
...  
Keyword(s):  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Hemorrhagic Transformation ◽  
Embolic Stroke ◽  
Intercellular Adhesion Molecule ◽  
Therapeutic Window ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Vascular Events ◽  
Protease Activated Receptor 1

We investigated the neuroprotective effect of atorvastatin in combination with delayed thrombolytic therapy in a rat model of embolic stroke. Rats subjected to embolic middle cerebral artery (MCA) occlusion were treated with atorvastatin at 4 h, followed by tissue plasminogen activator (tPA) at 6 or 8 h after stroke. The combination of atorvastatin at 4 h and tPA at 6 h significantly decreased the size of the embolus at the origin of the MCA, improved microvascular patency, and reduced infarct volume, but did not increase the incidence of hemorrhagic transformation compared with vehicle-treated control animals. However, monotherapy with tPA at 6 h increased the incidence of hemorrhagic transformation and failed to reduce infarct volume compared with the control group. In addition, adjuvant treatment with atorvastatin at 4 h and with tPA at 6 h reduced tPA-induced upregulation of protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, and concomitantly reduced cerebral microvascular platelet, neutrophil, and fibrin deposition compared with rats treated with tPA alone at 6 h. In conclusion, a combination of atorvastatin and tPA extended the therapeutic window for stroke to 6 h without increasing the incidence of hemorrhagic transformation. Atorvastatin blocked delayed tPA-potentiated adverse cerebral vascular events, which likely contributes to the neuroprotective effect of the combination therapy.

scholarly journals Effects of attapulgite dietary supplementation on sow performance in two commercial farms in Greece

2018 ◽  
Vol 68 (2) ◽  
pp. 193 ◽  
Author(s):  
V. KANOULAS ◽  
G. A. PAPADOPOULOS ◽  
G. ARSENOS ◽  
E. D. TZIKA ◽  
P. FORTOMARIS
Keyword(s):  
Litter Size ◽  
Repeated Measures ◽  
Average Daily Gain ◽  
Body Weight Loss ◽  
Control Group ◽  
Treatment Groups ◽  
Performance Indexes ◽  
Commercial Farms ◽  
Underlying Mechanisms ◽  
Reproductive Phases

The present study investigated the effects of attapulgite supplementation in sow diets during gestation and lactation on sow performance. The study comprised two reproductive phases (cycles) in two commercial farrow to finish farms: Farm A (capacity: 550 sows) and Farm B (capacity: 220 sows). The treatment groups were: a) control group (CN): the sows were fed a common gestation or lactation diet; b) attapulgite group (AT): the sows were fed the CN diet supplemented with attapulgite at 0,7% level; c) attapulgite plus group (AT+): the sows were fed the CN diet supplemented with attapulgite (0.7%) and a mix of enzymes, live yeast and amino acids (0.1%), at a total of 0.8% level. Within each cycle the sows included per treatment were: 24 for Farm A; 12 for Farm B. Initially data were analyzed per cycle and per each farm. Data from sows that completed both cycles within each farm, were analyzed by repeated measures analysis. Regarding sow parameters, sow body weight loss during lactation tended to be greater in AT sows compared to CN sows during cycle 1 in Farm B and was greater in AT and AT+ than CN sows in Farm A that completed both cycles (P=0.063 and P=0.023, respectively). A greater litter size 24h postpartum was observed in favour of AT compared to CN group during cycle 1 in Farm A and in sows that completed both cycles in Farm A (P=0.001 and P= 0.011, respectively). Litter size at weaning was greater in sows from the AT group than CN during cycle 1 and 2 in Farm A, in cycle 1 in Farm B and in sows that completed both cycles in Farm A (P=0.004, P=0.037, P=0.037, and P=0.022, respectively). Piglet weight at weaning and average daily gain during lactation were greater in AT group than CN and AT+ in sows that completed both cycles in Farm A (P=0.049 and P=0.040 respectively). Notable similar effects, although not statistically significant, were also observed in Farm B. This field study suggests that attapulgite supplementation in sow diets can improve performance indexes. Further research should investigate the underlying mechanisms involved.

scholarly journals ARL 17477, a Potent and Selective Neuronal NOS Inhibitor Decreases Infarct Volume after Transient Middle Cerebral Artery Occlusion in Rats

1996 ◽  
Vol 16 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Zheng G. Zhang ◽  
David Reif ◽  
James Macdonald ◽  
Wen Xue Tang ◽  
Dietgard K. Kamp ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cell Damage ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Arterial Blood ◽  
Mca Occlusion ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Cerebral Artery Occlusion

We tested the effects of administration of a selective neuronal nitric oxide synthase (nNOS) inhibitor, ARL 17477, on ischemic cell damage and regional cerebral blood flow (rCBF), in rats subjected to transient (2 h) middle cerebral artery (MCA) occlusion and 166 h of reperfusion (n = 48) and in rats without MCA occlusion (n = 25), respectively. Animals were administered ARL 17477 (i.v.): 10 mg/kg; 3 mg/kg; 1 mg/kg; N-nitro-L-arginine (L-NA) 10 mg/kg L-NA 1 mg/kg; and Vehicle. Administration of ARL 17477 1 mg/kg, 3 mg/kg and 10 mg/kg reduced ischemic infarct volume by 53 (p < 0.05), 23, and 6.5%, respectively. L-NA 1 mg/kg and 10 mg/kg increased infarct volume by 2 and 15%, respectively (p > 0.05). Administration of ARL 17477 (10 mg/kg) significantly (p < 0.05) decreased rCBF by 27 ± 5.3 and 24 ± 14.08% and cortical NOS activity by 86 ± 14.9 and 91 ± 8.9% at 10 min or 3 h, respectively, and did not alter mean arterial blood pressure (MABP). L-NA (10 mg/kg) significantly reduced rCBF by 23 ± 9.8% and NOS activity by 81 ± 7% and significantly (p < 0.05) increased MABP. Treatment with 3 mg/kg and 1 mg/kg ARL 17477 reduced rCBF by only 2.4 ± 4.5 and 0%, respectively, even when NOS activity was reduced by 63 ± 13.4 and 45 ± 15.7% at 3 h, respectively, (p < 0.05). The data demonstrate that ARL 17477 inhibits nNOS in the rat brain and causes a dose-dependent reduction in infarct volume after transient MCA occlusion.

Demonstration of therapeutic window of Cerebrolysin in embolic stroke: A prospective, randomized, blinded, and placebo-controlled study

2017 ◽  
Vol 12 (6) ◽  
pp. 628-635 ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Mei Lu ◽  
Talan Zhang ◽  
Chao Li ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Mean Difference ◽  
Embolic Stroke ◽  
Therapeutic Window ◽  
Cerebral Artery Occlusion

Background and aims In an effort to characterize the effects of Cerebrolysin for treatment of stroke that are essential for successful clinical translation, we have demonstrated that Cerebrolysin dose dependently enhanced neurological functional recovery in experimental stroke. Here, we conduct a prospective, randomized, placebo-controlled, blinded study to examine the therapeutic window of Cerebrolysin treatment of rats subjected to embolic stroke. Methods Male Wistar rats age 3–4 months (n = 100) were subjected to embolic middle cerebral artery occlusion. Animals were randomized to receive saline or Cerebrolysin daily for 10 consecutive days starting 4, 24, 48, and 72 h after middle cerebral artery occlusion. Neurological outcome was measured weekly with a battery of behavioral tests (adhesive removal test, modified neurological severity score (mNSS), and foot-fault test). Global test was employed to assess Cerebrolysin effect on neurological recovery with estimation of mean difference between Cerebrolysin and control-treated groups and its 95% confidence interval in the intent-to-treat population, where a negative value of the mean difference and 95% confidence interval < 0 indicated a significant treatment effect. All rats were sacrificed 28 days after middle cerebral artery occlusion and infarct volume was measured. Results Cerebrolysin treatment initiated within 48 h after middle cerebral artery occlusion onset significantly improved functional outcome; mean differences and 95% confidence interval were −11.6 (−17.7, −5.4) at 4 h, −7.1 (−13.5, −0.8) at 24 h, −8.4 (−14.2, −8.6) at 48 h, and −4.9 (−11.4, 1.5) at 72 h. There were no differences on infarct volume and mortality rate among groups. Conclusions With a clinically relevant rigorous experimental design, our data demonstrate that Cerebrolysin treatment effectively improves stroke recovery when administered up to 48 h after middle cerebral artery occlusion.

scholarly journals Photothrombotic Occlusion of Rat Middle Cerebral Artery: Histopathological and Hemodynamic Sequelae of Acute Recanalization

1988 ◽  
Vol 8 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Hitoshi Nakayama ◽  
W. Dalton Dietrich ◽  
Brant D. Watson ◽  
Raul Busto ◽  
Myron D. Ginsberg
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cortical Neurons ◽  
Cell Damage ◽  
Thrombus Formation ◽  
Infarct Volume ◽  
Brain Regions ◽  
Mca Occlusion ◽  
Temporary Occlusion ◽  
Mixed Pattern

The histopathological and hemodynamic consequences of photochemically induced middle cerebral artery (MCA) thrombosis and recanalization were studied in the rat. Recanalization of the thrombosed MCA segment was achieved by the topical application of nimodipine at 1 h following photochemically induced occlusion. Pathological consequences of permanent and temporary occlusion were compared by morphometric procedures 7 days following thrombus formation. Rats with permanent thrombosis exhibited consistent infarction of both striatum and cortex. MCA recanalization at 1 h was associated with a significant reduction in total infarct volume. In recanalized rats, small cortical infarcts, confined to the peripheral MCA territory, were observed in only three of six rats. In contrast, a mixed pattern of infarction and ischemic cell damage was documented throughout the striatum in all rats. Local CBF (ICBF), measured autoradiographically, was significantly reduced in the MCA territory following 1 h of MCA occlusion, especially within the striatum. At 1 h after recanalization, lCBF recovered within the previously ischemic brain regions to >50% of control. Perfusion deficits were detected by carbon black infusion within focal areas of the striatum following reperfusion. Thus, cortical neurons appear to tolerate 1 h of MCA occlusion in this model. In contrast, reperfusion following 1 h of photochemically induced MCA occlusion gives rise to selective injury to the striatum.

scholarly journals INF-β treatment to prolong t-PA treatment window in cerebral ischemia

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Kristopher D. Bosi, BS ◽  
Jui-Hung Yen, PhD
Keyword(s):  
Cerebral Ischemia ◽  
Immune Cell ◽  
Cell Damage ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Microglial Cells ◽  
Therapeutic Window ◽  
Expression Levels ◽  
First Line Therapy ◽  
Acute Cerebral Ischemia

Background and Hypothesis: Cerebral ischemia is the 2nd leading cause of death worldwide. The pathological hallmarks of cerebral ischemia are cell damage, degradation of the blood brain barrier (BBB), and inflammation followed by resident microglia activation, peripheral immune cell infiltration and subsequent secondary neurodegeneration. The first line therapy for ischemic stroke is the thrombolytic, tPA. However, only ten percent of patients are eligible for this treatment – primarily due to the risk of cerebral hemorrhage, secondary to BBB breakdown. Less than ten percent of individuals with acute cerebral ischemia are eligible for tPA. The objective of this study is to establish whether matrix metalloproteinase (MMP) activity, implicated in exacerbating the cerebral infarct volume seen with delayed tPA treatment, can be suppressed with Interferon-β (IFN-β) and thus extend the therapeutic window of tPA. Experimental Design: We first investigated the therapeutic effect of IFN-β co-administered with t-PA in the mouse model of transient middle cerebral artery occlusion/reperfusion. Second, using immunoblotting technique we investigated the expression levels of MMPs in brain endothelial and microglial cells following various treatment combinations of TNFα and PGE2, t-PA, and INF-β. Results: First, we demonstrated that IFN-β coadministered with tPA reduces the infarct size in ischemic brains. Second, we demonstrated in microglial cells that MMP-9 expression induced by TNFα, PGE2, and tPA can be suppressed by IFN-β treatment. Our experiments to demonstrate the expression levels of MMP-3 and MMP-9 in brain endothelial cells require further optimization. Conclusion and Potential Impact: Overall these data indicate that IFN-β treatment is a viable therapeutic candidate to suppress the deleterious effects seen in delayed tPA treatment in the setting of acute cerebral ischemia. Furthermore, our preliminary data indicate that the molecular target of IFN-β, in this setting, belong to the MMP family of proteins.

Neuroprotective activity of tamoxifen in permanent focal ischemia

2003 ◽  
Vol 99 (1) ◽  
pp. 138-142 ◽  
Author(s):  
Harold K. Kimelberg ◽  
Yiqiang Jin ◽  
Carol Charniga ◽  
Paul J. Feustel
Keyword(s):  
Rat Model ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Neuroprotective Activity ◽  
Therapeutic Window ◽  
Protective Effects ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print ◽  
Permanent Focal Ischemia

Object. The authors have previously shown that tamoxifen is effective in protecting brain tissue from ischemic injury in a rat model of reversible focal ischemia. In this study the authors tested whether similar protective effects are found in a rat model of permanent focal ischemia (permanent middle cerebral artery [MCA] occlusion). Methods. Tamoxifen (20 mg/kg) was given either before or at 1, 3, or 6 hours after permanent MCA occlusion in rats, with sustaining doses given every 12 hours thereafter. The median infarct volume measured after 72 hours was 113 mm3 for the vehicle (dimethyl sulfoxide) groups, compared with 31 mm3 for pretreatment, and 14, 27, and 98 mm3 for treatment beginning at 1, 3, and 6 hours, respectively, after permanent MCA occlusion. The infarct reductions in the pretreated and 1- and 3-hour post—MCA occlusion treatment groups were statistically significant (p < 0.05). At 3 hours after permanent MCA occlusion, tamoxifen also significantly reduced the infarct size at a lower dose of 5 mg/kg but not at 1 mg/kg; the same sustaining doses of 5 and 1 mg/kg were given every 12 hours. Conclusions. Tamoxifen is as effective in a permanent model of focal ischemia as it is in the reversible model, and the therapeutic window of 3 hours after initiation of ischemia is identical. This effectiveness is likely due to several properties of the drug, including its known ability to cross the blood—brain barrier. Because tamoxifen has been administered safely in humans for treatment of gliomas at similarly high doses to those used in this study, it may be clinically useful as a treatment for ischemic stroke.

Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ifechukwude Joachim Biose ◽  
Katie E Salmeron ◽  
Anthony Parker ◽  
Ann Stowe ◽  
Gregory Bix
Keyword(s):  
Physical Activity ◽  
Ischemic Stroke ◽  
Infarct Volume ◽  
Exercise Group ◽  
Artery Occlusion ◽  
Control Group ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Voluntary Physical Activity ◽  
Wheel Activity

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm 3 ; P<0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.

scholarly journals Gaining Insights To Understand The Anti-Inflammatory Functions of Mesenchymal Stem Cell-Derived Conditioned Medium In Combination With Stigmasterol In IL-1β-Stimulated Rat Articular Chondrocytes – An In-Vitro Approach

2021 ◽  
Author(s):  
Samuel Joshua Pragasam Sampath ◽  
Subha Narayan Rath ◽  
Nagasuryaprasad Kotikalapudi ◽  
Vijayalakshmi Venkatesan
Keyword(s):  
Conditioned Medium ◽  
Combination Treatment ◽  
Articular Chondrocytes ◽  
Cartilage Destruction ◽  
Joint Disease ◽  
Control Group ◽  
Treatment Groups ◽  
Per Se ◽  
Anti Inflammatory

Abstract Osteoarthritis (OA) is the most prevalent joint disease predominantly characterized by inflammation which drives cartilage destruction. Mesenchymal stem cells-condition medium (MSC-CM) or the secretome is enriched with bioactive factors and possesses anti-inflammatory and regenerative effects. The present study aimed at evaluating the effects of combining MSC-conditioned medium with stigmasterol compared with per se treatments in alleviating interleukin-1beta (IL-1β)-induced inflammation in rat chondrocytes. Stigmasterol is a phytosterol exhibiting anti-inflammatory effects. IL-1β (10ng/ml) was used to induce inflammation and mimic OA in-vitro in primary rat articular chondrocytes. The IL-1β-stimulated chondrocytes were treated with MSC-CM, stigmasterol, and a combination of MSC-CM and stigmasterol for 24 hours. Cell viability was measured using MTT assay. Protein expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), collagen II (COL2A1) and matrix metalloproteinase (MMP)‑13 were evaluated by immunofluorescence. Gene expression levels of MMP-3, MMP-13 and A Disintegrin-like and Metalloproteinases with Thrombospondin Motifs (ADAMTS)-5 were measured using qRT-PCR. NF-κB signaling pathway was studied using western blotting. A significant reduction in the expression of iNOS, IL-6, MMP-3, MMP-13 and ADAMTS-5 and a significant increase in COL2A1 expression was observed in the rat chondrocytes across all the treatment groups. However, the combination treatment of MSC-CM and stigmasterol remarkably reversed the IL-1β-induced pro-inflammatory/pro-catabolic responses to near normal levels comparable to the control group. The combination treatment (MSC-CM+stigmasterol) elicited a superior anti-inflammatory/anti-catabolic effect by inhibiting the IL-1β-induced NF-κB activation evidenced by the negligible phosphorylation of p65 and IκBα subunits, thereby emphasizing the benefit of the combination therapy over the per se treatments.

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