Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy

AbstractThere are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar’s brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

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Anti-Diabetic Retinopathy Potential of Noni: The beneficial effect and possible mechanism

Diabetes and Islet Biology ◽

10.31579/2641-8975/021 ◽

2020 ◽

Vol 3 (1) ◽

pp. 01-21

Author(s):

Faisal Ali

Keyword(s):

Diabetic Retinopathy ◽

Prolonged Exposure ◽

Morinda Citrifolia ◽

In Vivo Studies ◽

Laboratory Research ◽

Tropical Region ◽

Bioactive Substances ◽

High Blood Glucose

Noni (Morinda citrifolia L.) is being evaluated in laboratory research for its benefits as an antioxidant and immunity booster, as well as for its properties to prevent tumors and cure diabetes. The vast spread of Noni in tropical region of the globe, from America reaching to Africa and Southeast Asia, contributed in enhancing its usage and potency due to the diversity in harvest zone. Noni parts comprise fruits, seeds, leaves, and flowers are being used for individual nutritional and therapeutical values. Nevertheless, the fruit is widely characterized to contain the most valuable bioactive substances. On the other hand, diabetic retinopathy (DR) is a microvascular disorder impacting the small blood vessels in the retina, which includes microaneurysms, retinal hemorrhages, and hard exudates results from prolonged exposure to high blood glucose levels. The anti-diabetes effect of Noni extract and juice has been examined but the beneficial role of Noni and its potential mechanisms against the development of diabetic retinopathy phenotype is still ambiguous. This review, therefore, will discusses in details the pharmacological actions of M. citrifolia fruit, along with their isolated phytochemical compounds on diabetic retinopathy markers, through describing the conducted in vitro and in vivo studies as well as clinical data.

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Safety Evaluation of Multiple Strains ofLactobacillus plantarumandPediococcus pentosaceusin Wistar Rats Based on the Ames Test and a 28-Day Feeding Study

The Scientific World JOURNAL ◽

10.1155/2014/928652 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Cheng-Chih Tsai ◽

Sew-Fen Leu ◽

Quan-Rong Huang ◽

Lan-Chun Chou ◽

Chun-Chih Huang

Keyword(s):

Wistar Rats ◽

Clinical Chemistry ◽

Toxicity Study ◽

Bacterial Strains ◽

Oral Toxicity ◽

Short Term ◽

Mutagenic Potential ◽

Multiple Strains

Three lactic acid bacterial strains,Lactobacillus plantarum, HK006, and HK109, andPediococcus pentosaceusPP31 exhibit probiotic potential as antiallergy agents, both in vitro and in vivo. However, the safety of these new strains requires evaluation when isolated from infant faeces or pickled cabbage. Multiple strains (HK006, HK109, and PP31) were subject to a bacterial reverse mutation assay and a short-term oral toxicity study. The powder product exhibited mutagenic potential inSalmonellaTyphimurium strains TA98 and TA1535 (with or without metabolic activation). In the short-term oral toxicity study, rats received a normal dosage of 390 mg/kg/d (approximately9×109 CFU/kg/d) or a high dosage of 1950 mg/kg/d (approximately4.5×1010 CFU/kg/d) for 28 d. No adverse effects were observed regarding the general condition, behaviour, growth, feed and water consumption, haematology, clinical chemistry indices, organ weights, or histopathologic analysis of the rats. These studies have demonstrated that the consumption of multiple bacterial strains is not associated with any signs of mutagenicity ofS.Typhimurium or toxicity in Wistar rats, even after consuming large quantities of bacteria.

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Abstract 15142: Endogenous Cardiac Stem Cells’ Activation in Response to Injury Potentiates Their Regenerative Ability

Circulation ◽

10.1161/circ.132.suppl_3.15142 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Andrew J Smith ◽

Iolanda Aquila ◽

Beverley J Henning ◽

Mariangela Scalise ◽

Bernardo Nadal-Ginard ◽

...

Keyword(s):

Stem Cells ◽

Cardiac Injury ◽

Fold Increase ◽

Cardiac Stem Cells ◽

Post Injury ◽

Activated State ◽

Potential Benefits ◽

Therapeutic Avenue

The identification of resident, endogenous cardiac stem cells (eCSCs) has re-shaped our understanding of cardiac cellular physiology, while offering a significant potential therapeutic avenue. The biology of these cells must be better understood to harness their potential benefits. We used an acute dose (s.c.; 5mgkg-1) of isoproterenol (ISO) to induce diffuse cardiac injury, with associated eCSC activation, in rats. As peak eCSC activation was at 24 hours post ISO-injury, c-kitpos eCSCs were isolated, characterised and their potential for growth and regenerative potential was assessed in vitro and in vivo, respectively. Activated eCSCs showed increased cell cycling activity (51+1% in S- or G2/M phases vs. 9+2% of quiescent), Ki67 expression (56+7% vs. 10+1%) and TERT expression (14-fold increase vs. quiescent). When directly harvested in culture, activated eCSCs showed augmented proliferation, clonogenicity and cardiosphere formation compared to quiescent eCSCs. Activated eCSCs showed increases in expression of numerous growth factors, particularly HGF, IGF-1, TGF-β, periostin, PDGF-AA and VEGF-A. Furthermore, significant alterations were found in the miRnome, notably increased miR-146b and -221, and decreased miR-192 and -351. ISO+5FU was administrated to mice to induce a model of chronic dilated cardiomyopathy, which is characterized by the ablation of eCSCs and the absence of cardiomyocyte replenishment. In these mice with chronic heart failure, freshly isolated quiescent eCSCs or activated eCSCs (2d post-ISO) were injected through the tail vein. 28 days after injection, activated but not quiescent eCSCs re-populated the resident CSC pool, promoted robust new cardiomyocyte formation and improved cardiac function when compared to saline-treated mice. Dual-labelling with BrdU and EdU at selected stages after ISO injury determined that activated eCSCs returned to a quiescent level by 10 weeks post-injury. In conclusion, CSCs rapidly switch from a quiescent to an activated state to match the myocardial needs for myocyte replacement after injury and then spontaneously go back to quiescence. Harnessing the molecules regulating this process may open up future novel approaches for effective myocardial regeneration.

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Upregulation of PKR pathway mediates glucolipotoxicity induced diabetic cardiomyopathy in vivo in wistar rats and in vitro in cultured cardiomyocytes

Biochemical Pharmacology ◽

10.1016/j.bcp.2020.113948 ◽

2020 ◽

Vol 177 ◽

pp. 113948

Author(s):

Sureshbabu Mangali ◽

Audesh Bhat ◽

Kirtikumar Jadhav ◽

Jaspreet Kalra ◽

Dharmarajan Sriram ◽

...

Keyword(s):

Diabetic Cardiomyopathy ◽

Wistar Rats ◽

Cultured Cardiomyocytes

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Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

Scientific Reports ◽

10.1038/s41598-019-52398-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Jyoti Kaushik ◽

Simran Tandon ◽

Rishi Bhardwaj ◽

Tanzeer Kaur ◽

Surinder Kumar Singla ◽

...

Keyword(s):

Body Weight ◽

Aqueous Extract ◽

Kidney Stones ◽

Wistar Rats ◽

Lethal Dose ◽

Tribulus Terrestris ◽

Oral Toxicity ◽

Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

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Injectable mechanical pillows for attenuation of load-induced post-traumatic osteoarthritis

Regenerative Biomaterials ◽

10.1093/rb/rbz013 ◽

2019 ◽

Vol 6 (4) ◽

pp. 211-219

Author(s):

Derek T Holyoak ◽

Tibra A Wheeler ◽

Marjolein C H van der Meulen ◽

Ankur Singh

Keyword(s):

Knee Joint ◽

Joint Damage ◽

Mechanical Trauma ◽

Protective Effects ◽

Post Injury ◽

On Demand ◽

Post Traumatic ◽

Anti Inflammatory

Abstract Osteoarthritis (OA) of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals. The disease manifests as joint damage and synovial inflammation. Post-traumatic osteoarthritis (PTOA) is a specific form of OA caused by mechanical trauma to the joint. The progression of PTOA is prevented by immediate post-injury therapeutic intervention. Intra-articular injection of anti-inflammatory therapeutics (e.g. corticosteroids) is a common treatment option for OA before end-stage surgical intervention. However, the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids. Here, we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol (PEG-4MAL) hydrogel system as a ‘mechanical pillow’ to cushion the load-bearing joint, withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone, an anti-inflammatory agent. PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions. Importantly, the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking. Although dexamethasone had minimal protective effects on OA-like pathology in our studies, the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.

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Glial imaging during synapse remodeling at the neuromuscular junction

Neuron Glia Biology ◽

10.1017/s1740925x09990421 ◽

2008 ◽

Vol 4 (4) ◽

pp. 319-326 ◽

Cited By ~ 1

Author(s):

Yi Zuo ◽

Derron Bishop

Keyword(s):

Neuromuscular Junction ◽

Schwann Cells ◽

Synapse Formation ◽

Ultrastructural Organization ◽

Post Injury ◽

Electron Microscopic ◽

Cell Dynamics ◽

Transmission Electron

Glia are an indispensable structural and functional component of the synapse. They modulate synaptic transmission and also play important roles in synapse formation and maintenance. The vertebrate neuromuscular junction (NMJ) is a classic model synapse. Due to its large size, simplicity and accessibility, the NMJ has contributed greatly to our understanding of synapse development and organization. In the past decade, the NMJ has also emerged as an effective model for studying glia–synapse interactions, in part due to the development of various labeling techniques that permit NMJs and associated Schwann cells (the glia at NMJs) to be visualized in vitro and in vivo. These approaches have demonstrated that Schwann cells are actively involved in synapse remodeling both during early development and in post-injury reinnervation. In vivo imaging has also recently been combined with serial section transmission electron microscopic (ssTEM) reconstruction to directly examine the ultrastructural organization of remodeling NMJs. In this review, we focus on the anatomical studies of Schwann cell dynamics and their roles in formation, maturation and remodeling of vertebrate NMJs using the highest temporal and spatial resolution methods currently available.

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Catalytic nanomedicine: A new field in antitumor treatment using supported platinum nanoparticles. In vitro DNA degradation and in vivo tests with C6 animal model on Wistar rats

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2010.01.043 ◽

2010 ◽

Vol 45 (5) ◽

pp. 1982-1990 ◽

Cited By ~ 31

Author(s):

T. López ◽

F. Figueras ◽

J. Manjarrez ◽

J. Bustos ◽

M. Alvarez ◽

...

Keyword(s):

Animal Model ◽

Platinum Nanoparticles ◽

Wistar Rats ◽

Dna Degradation ◽

Supported Platinum ◽

In Vivo Tests

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Concomitant release of sialic acids and calcium by neuraminidase from rat aorta in situ

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1988.0068 ◽

1988 ◽

Vol 235 (1279) ◽

pp. 139-144 ◽

Cited By ~ 2

Keyword(s):

Sialic Acid ◽

Wistar Rats ◽

Rat Aorta ◽

Sialic Acids ◽

Molar Ratio ◽

Male Wistar Rats

Male Wistar rats were heparinized and killed with pentobarbital. The upper and lower ends of the aortae were cannulated and the blood was washed out with saline until the washings contained calcium and sialic-acid-reacting material at minimal concentrations. The aortae were perfused with neuraminidase for 15 min. This caused the appearance of calcium as well as of sialic acids in the perfusate in total amounts of about 5.3 nmol and about 3.6 nmol per aorta respectively. The molar ratio of about 1.5 is sufficiently close to that determined for the association of calcium with sialic acids in vitro to suggest that their association is similar in vivo .

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