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At least 19 recordsLinked to original sources

PubMed1978

Experimental Haemophilus influenzae type b meningitis: immunological investigation of the infant rat model.

Infant rats inoculated intraperitoneally with Haemophilus influenzae type b develop bacteremia and meningitis. Rats were infected at 10 to 12 days of age and studied for the development of serum anticapsular antibody and bactericidal and opsonizing activity. Seven and 11 weeks after inoculation, convalescent animals showed a higher frequency of anticapsular antibody responses than uninfected controls, but 35 to 40% of the infected group had undetectable levels of anticapsular antibody (<0.10 mug/ml). In contrast, all of the convalescent animals, but none of the controls, showed moderate titers of serum bactericidal activity; and bactericidal activity persisted after absorption of the convalescent sera with type b capsule. Bactericidal activity was detected primarily in the eluted fraction corresponding to a molecular weight of 150,000 and was present in the offspring of convalescent females. Offspring of convalescent females were protected against challenge with H. influenzae type b, and control offspring could also be protected by passive immunization with convalescent serum which lacked detectable anticapsular antibody. Convalescent serum samples efficiently opsonized H. influenzae type b, and this activity persisted after absorption of the serum with capsular antigen. These data are consistent with the hypothesis that antibody to the noncapsular surface antigens of H. influenzae type b play an important role in host defenses.

Animals↗

PubMed2026

Generation of a New Immunodeficient Rat Model of Retinal Degeneration With LSL TdTomato Reporter and TdTomato-Pcp2 Expression.

PURPOSE: The purpose of this study was to develop a fluorescently labeled immunodeficient retinal degenerate (RD) rat model for studying photoreceptor degeneration and transplant-host connectivity using the Cre-lox system. METHODS: We developed gene constructs for CAG-LSL-TdTomato (expressing floxed TdTomato) and Pcp2-Cre (marker for ON-bipolar cells) that were injected into rat embryos. The LSL TdTomato reporter strain, created on immunodeficient RhoS334ter-3 rats (RRRC #539), was bred to homozygosity (strain SD-Foxn1rnuTg((Rho-S334X)3,CAG-TdTomato)1010Mjsuc, RRRC #1055, "RNT"). The gene construct Pcp2-Cre was injected into Long-Evans (LE) rat embryos, resulting in two Pcp2-cre founders (strain PCP2 Cre-1105 RKI, "Pcp2"), with targeted and targeted/random insertion of the transgene. F1 offspring were bred to homozygosity and immunodeficiency. To test whether TdTomato expression can be induced in "RNT" rats expressing floxed TdTomato, retinal explants of P9 "RNT" rats were exposed to AAV-PHP.eB-hSyn-myc-Cre (AAV-Syn-Cre) virus. Homozygous rats of both strains ("RNT" and Pcp2-Cre) were crossbred to generate RD TdTomato-Pcp2 ("RTP") rats. Retinas were stained for various retinal markers. GFP-expressing rat retinas were transplanted to 6-week-old "RTP" rats and analyzed after 37 and 77 days. RESULTS: AAV-Syn-Cre induced TdTomato expression in "RNT" retinas. TdTomato-Pcp2 RD rats developed RD similar to the original Rho S334ter-3 rats. Retinas with targeted Pcp2-Cre insertion showed TdTomato in retinal interneurons, overlapping with Pcp2-staining ON bipolar cells, and cones. Retinas with random Pcp2-Cre insertion exhibited additional TdTomato in many other cells. Pcp2-TdTomato expression defined transplant-host boundaries. CONCLUSIONS: We created a unique RD rat model for studying retinal transplant connectivity which can also be used to generate RD rats with other cell-specific labels. TRANSLATIONAL RELEVANCE: This newly created rat is useful for cell therapy and retinal degeneration studies.

Animals↗

PubMed1978

Rat model of experimental endocarditis.

A simple model of infective endocarditis was produced in rats. With the aid of a guide wire, polyethylene catheters were passed into the left ventricle through the right carotid artery of Sprague-Dawley rats weighing 300 to 350 g. A volume of 1 ml of an overnight culture of Streptococcus mitis, Staphylococcus aureus, or Streptococcus faecalis was intravenously injected 1 to 2 days after catheterization. Bacterial titers of Streptococcus mitis in vegetations were about 10(4)-fold greater than in other tissues. Blood cultures were always positive after 6 h. Mortality was 19% at 1 week and 82% at 2 weeks. Catheters were pulled 24 h after infection, and vegetation titers of greater than 7.0 log10 colony-forming units per g were sustained at 5 days. In intravenously infected rats without catheters, blood and tissues were sterile after 3 to 5 days. With Staphylococcus aureus, vegetations had greater than 9.0 log10 colony-forming units and with Streptococcus faecalis 8.8 +/- 0.3 log10 colony-forming units per g at 2 days. The rat model of infective endocarditis should prove to be suitable for further pathological and therapeutic studies.

Animals↗

PubMed1979

A rat model of neurobehavioral development.

The neurobehavioral evolution of the normally growing rat has been investigated by means of a series of reflex, motor and sensory tests from birth up to weaning. A sequential development of behavioral responses has been assessed over this 21-days period, and 2nd week following birth representing an important step in the neurobehavioral maturation of the rat. This rat model may be considered as an useful reference to evaluate changes that may be induced by pharmacological and toxicological agents in the developing exposed rat.

Animals↗

PubMed2026

Kidney mitochondrial complex I dysfunction in a juvenile rat model of diabetic ketoacidosis.

BACKGROUND: The pathobiology of acute kidney injury during diabetic ketoacidosis (DKA) is not completely understood. We hypothesized that mitochondrial function is impaired during DKA as a mechanism of acute kidney injury. METHODS: We isolated kidney samples from 4 to 5 week-old rats with normoglycemia (NG, controls; n = 7), hyperglycemia (HG; n = 5), acute DKA (DKA; n = 5), and after 24 h of DKA treatment (DKA-24; n = 5). Kidney tissue homogenates were prepared from frozen tissue for measurement of mitochondrial electron transport system (ETS) complex I + III, II + III, and IV activity and citrate synthase activity using spectrophotometry and ETS complex protein expression using Western blots. RESULTS: Mitochondrial ETS complex I + III activity (mean ± SD) exhibited a stepwise decrease from HG (113 ± 54 nmol/min/mg tissue protein) to DKA (64 ± 32; p < 0.05 compared to NG) and trended toward NG control levels (143 ± 37) in DKA-24 (135 ± 39). Mitochondrial content, including citrate synthase activity and ETS complex proteins I, II, IV, and V, did not differ between groups, except that ETS complex III increased in HG and DKA and subsequently decreased in DKA-24. CONCLUSIONS: In a juvenile rat model of DKA, increasing glycemic stress caused a reversible change in kidney mitochondrial complex I function and complex III expression. IMPACT: Acute kidney injury during diabetic ketoacidosis (DKA) increases risk of future diabetic kidney disease, but the underlying pathobiology is not understood. In a juvenile rat model of DKA, we found that increasing glycemic stress caused a reversible change in kidney mitochondrial complex I function and complex III expression. These data support further investigation to determine if mitochondrial dysfunction may contribute to DKA-related acute kidney injury.

Letter↗

PubMed2026

Mechanism of Action of Hedyotis diffusa Extract in a Rat Model of Acute Lung Injury Based on Transcriptomic Analysis.

OBJECTIVE: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF-α interleukin-1β IL-1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of -14.74, -14.92, -17.58, -23.04, and -16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively. CONCLUSIONS: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.

Hedyotis diffusa↗

PubMed2026

Hyperpolarized NMR study of the impact of alzheimer's disease on diabetes using a novel rat model.

Most researchers have long focused on linkage between type 2 diabetes (T2D) and the increased risk of Alzheimer's disease (AD) but have often overlooked whether AD modulates T2D. Investigating the reciprocal interaction between two complex diseases provides perspectives on the mechanistic linkage. The endeavor, however, confronts challenges without a robust rodent model that develops T2D and AD as the animal ages. Cross breeding a T2D rat with a hemizygous TgF344AD +/- rat that contains the mutant human amyloid precursor protein (APPsw) and the presenilin 1 (PS1ΔE9) genes has produced a new T2D-AD +/- rat model. The T2D-AD +/- rat expresses both the T2D and AD phenotypes as the animal ages. As AD progresses, the time to T2D onset decreases, and the diabetes severity increases. Hyperpolarized NMR experiments using dynamic nuclear polarization (DNP) show that T2D and T2D-AD rats share a common metabolic impairment in the brain pyruvate dehydrogenase (PDH) activity as reflected in the NMR determined decline in the bicarbonate/lactate (bic/lac) ratio. The bic/lac ratio decreases in both T2D and T2D-AD brain. AD exacerbates the decline of the bic/lac ratio.

Animals↗

PubMed1979

Functional cell compartments in a rat model for human acute myelocytic leukaemia.

Functional cell compartments were studied in a rat model for human acute myelocytic leukaemia (AML). This was done by tracing the distribution of injected 51Chromium-labelled leukaemic cells in the body. It was concluded that two functional compartments can be distinguished in acute leukaemia, i.e., a rapidly exchangeable pool of cells (including the circulating blood pool, the marginal noncirculating blood pool and the rapidly exchangeable tissue pool; RETP) and a slowly exchangeable tissue pool (SETP). The sizes of these various compartments were roughly quantified at various stages of the disease by calculations based on the principle of isotope dilution and organ weight measurements. As the leukaemia progresses, the size of the SETP increased significantly relative to the size of the RETP. Simultaneously, the exchange rates of leukaemic cells between the organs and the blood decrease. The blood transit time of leukaemic cells was also significantly prolonged, as is the case in human AML.

Animals↗

PubMed1979

A rat model (using a semipurified diet) of the fetal alcohol syndrome.

A semipurified liquid diet was used to develop a chronic rat model of the fetal alcohol syndrome. Control female rats gained weight normally, reproduced normally, and gave birth to normal litters on this diet. Increased neonatal mortality, decreased neonatal weights, and altered sex ratios were observed in offspring of experimental alcoholic animals. Preliminary histological results include a mild delay in cell lamination patterns in the cerebral cortex at 4 days postnatal in alcoholic offspring as well as decreased formation of dendritic spines at 7 days postnatal.

Animals↗

PubMed2026

Early Fibrotic Remodeling Remains Responsive to Autologous Fat Grafting: Histological Findings in a Rat Model.

BACKGROUND/AIM: Fibrosis-associated soft tissue remodeling involves progressive alterations in extracellular matrix composition, vascular architecture and tissue biomechanics. Early fibrotic lesions may remain biologically responsive before irreversible sclerosis develops. This study evaluated the histological evolution of bleomycin-induced soft tissue remodeling and the effects of autologous fat grafting in a rat model. MATERIALS AND METHODS: Twenty female Wistar rats received subcutaneous bleomycin (1 mg/kg/day for three consecutive days) to induce localized soft tissue remodeling. Autologous fat grafting was performed 17 days later. Clinical assessment was conducted at baseline, Day 17 and Day 31 using a standardized semi-quantitative score evaluating erythema, edema, skin elasticity, cutaneous mobility and ulceration or necrosis. Histological analysis was performed at predefined timepoints. RESULTS: Bleomycin induced reproducible early fibrotic remodeling characterized by collagen deposition, stromal hypercellularity, vascular remodeling and architectural distortion. The mean composite clinical score increased from 0 at baseline to 9.10±1.75 on Day 17 and decreased to 7.75±1.35 after fat grafting on Day 31 (p=0.00024). Histological examination demonstrated persistent fibrotic septa, fibroblast proliferation, vascular reorganization and partial integration of grafted adipose tissue, indicating ongoing tissue remodeling. CONCLUSION: Bleomycin-induced remodeling produced reproducible early fibrotic changes in dermal and subcutaneous tissues. Autologous fat grafting was associated with significant clinical improvement and histological evidence of continued tissue reorganization. This model supports investigation of regenerative therapies targeting early fibrosis-associated soft tissue remodeling.

Animals↗

PubMed1978

Decreased virulence of gentamicin-resistant strains of Pseudomonas aeruginosa in a rat model.

Previous studies have reported that GR strains of Pseudomonas aeruginosa were less likely to cause serious infections. In the present study, this clinical observation of decreased virulence of GR strains of P. aeruginosa was documented in Andriole's rat model. A significantly higher mortality in rats was noted with GS strains of P. aeruginosa (MIC less than 10 microgram/ml) compared to moderately resistant strains (MIC 12.5 to 312 microgram/ml) and highly resistant strains (MIC greater than 312 microgram/ml). Slower growth rates of GR strains of P. aeruginosa were observed in both the lag and the log phases as compared to GS strains. Average counts of in vivo quantitative blood cultures with the use of GR strains were lower at 30 min, 8 hr, and 24 hr compared to those with GS strains. The mortality in mice injected intraperitoneally with CFS's from GS strains (MIC 0.78 to 3.125 microgram/ml) was significantly higher at 8 and 24 hr than those injected with supernatants from GR strains (MIC 25 to 400 microgram/ml). Human neutrophils killed GR and GS strains of P. aeruginosa equally. Decreased virulence of GR strains of P. aeruginosa may be due in part to slower growth rates and to a decreased ability to produce heat-labile toxic components.

Animals↗

PubMed2025

Purkinje cell development and degeneration in the spastic Han-Wistar rat model of ataxia.

Hereditary ataxia is a neurodegenerative disorder notable for its early onset, with symptoms appearing in patients as young as two years old. Although affected individuals exhibit severe motor deficits and early mortality rates, the timeline of Purkinje cell loss remains unclear. To address this gap, we used the spastic Han-Wistar rat model, which harbors an unknown homozygous recessive variant that causes Purkinje cell loss. Here, we aimed to determine the onset and temporal progression of Purkinje neuronal loss in the spastic Han-Wistar model. To achieve this, we employed immunohistochemistry, Hematoxylin and Eosin histology, and neuronal density quantification. Behavioral testing demonstrated early-onset, progressive motor impairment in mutant rats, which coincided with a gradual loss of Purkinje cells in the cerebellum. Additionally, guided by pedigree analysis from a previous study indicating autosomal recessive inheritance for this ataxia, we performed whole-genome shotgun sequencing of a parent-offspring trio to identify amino acid-changing mutations consistent with this pattern. We used Sanger sequencing to exclude non-causal candidates. Together, our findings provide new insights into the onset and genetic complexity of ataxia, refining the value of the spastic Han-Wistar rat as a model for investigating mechanisms underlying hereditary ataxia and broader neurodegenerative disorders.

Hereditary ataxia↗

PubMed2024

Progressive cardiomyopathy with intercalated disc disorganization in a rat model of Becker dystrophy.

Becker muscular dystrophy (BMD) is an X-linked disorder due to in-frame mutations in the DMD gene, leading to a less abundant and truncated dystrophin. BMD is less common and severe than Duchenne muscular dystrophy (DMD) as well as less investigated. To accelerate the search for innovative treatments, we developed a rat model of BMD by deleting the exons 45-47 of the Dmd gene. Here, we report a functional and histopathological evaluation of these rats during their first year of life, compared to DMD and control littermates. BMD rats exhibit moderate damage to locomotor and diaphragmatic muscles but suffer from a progressive cardiomyopathy. Single nuclei RNA-seq analysis of cardiac samples revealed shared transcriptomic abnormalities in BMD and DMD rats and highlighted an altered end-addressing of TMEM65 and Connexin-43 at the intercalated disc, along with electrocardiographic abnormalities. Our study documents the natural history of a translational preclinical model of BMD and reports a cellular mechanism for the cardiac dysfunction in BMD and DMD offering opportunities to further investigate the organization role of dystrophin in intercellular communication.

Animals↗

PubMed2026

Occupationally relevant vibrations and the brain: frequency-dependent proteomics signatures in a rat model.

INTRODUCTION: Occupational exposure to whole-body vibration (WBV), particularly in agricultural environments, has been associated with adverse cognitive and physiological effects. This study examined the neurophysiological impact of WBV in a rat model at 4 Hz and 30 Hz, frequencies representative of off-road and on-road vehicle operation. METHODOLOGY: Forty-four Sprague-Dawley rats were assigned to control (0 Hz), low-frequency (4 Hz), or high-frequency (30 Hz) vibration conditions. After three days of exposure, brain tissues were collected and analyzed using mass spectrometry-based proteomics to identify differentially expressed proteins. RESULTS: Proteomic profiling revealed distinct, frequency-dependent alterations in brain protein expression. Compared with controls, 32 cognition-related proteins were differentially regulated at 4 Hz and 29 at 30 Hz, with 13 differing between the two vibration conditions. Principal component analysis showed clear separation among groups, indicating unique proteomic signatures for each exposure frequency. Functional enrichment and protein-protein interaction analyses demonstrated involvement of synaptic plasticity, cytoskeletal organization, calcium regulation, and neurotransmitter release. Exposure to 4 Hz was associated with the upregulation of proteins involved in calcium homeostasis and synaptic integrity, suggesting potential disruption of cognitive processes. In contrast, 30 Hz increased the expression of proteins related to axonal guidance and neuroprotection, indicating a less clearly adverse response that may reflect adaptive or potentially beneficial effects. DISCUSSION: These findings provide new insight into biological mechanisms underlying WBV-induced cognitive changes and underscore the importance of vibration frequency in shaping neurophysiological outcomes. They also establish a foundation for future studies integrating proteomics with behavioural assessments in animals and humans.

Animals↗

PubMed1975

Evaluation of four antiviral agents in the treatment of herpes simplex encephalitis in a rat model.

Three hundred four animals were used for the systematic evaluation of the in vivo efficacy of 5-iodo-2'-deoxyuridine (IUDR), cytosire arabinoside, 9-beta-arabinofuranosyladenine, and isoprinosine in the therapy of herpes simplex encephalitis in an adult rat model. Type 1 herpes simplex virus was inoculated intracerabrally, and drug was administered by the intraperitoneal route. All experiments included tests for toxicity and viral controls, Eight sets of experiments were used for evaluation of ttherapy with IUDR; the inoculum ranged from 64 to 2,000 TCID50, dose of drug from 0.1 mg/g to 1.0 mg/g per day, and duration of therapy from one to five days. There was no significant improvement in the number of animals surviving or in the survival time when the viral controls were compared with mice in treated groups. A slight trend toward increased survival time and decreased titer of virus in the brains of animals treated with IUDR was noted in the group that received the largest dose. Three or four sets of experiments were used to evaluate each of the other three antiviral drugs. Results were similar to those reported for IUDR. These results indicate a need for further studies, including investigations of the pharmacology and toxicity of these antiviral agents, to establish more clearly the dosages of drug that are therapeutic, those that are toxic, and ratios of these dosages.

Acetanilides↗

PubMed2026

Altered Excitation-Inhibition Balance and mGluR1/5-Driven Plasticity in the Motor Cortical Surface in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by progressive dopaminergic degeneration and maladaptive motor cortical plasticity. However, the cellular pathways underlying cortical surface activity in the primary motor cortex (M1) remain unclear, despite serving as a potential target for electrotherapy. We investigated the excitatory-inhibitory (E-I) balance and synaptic plasticity of superficial M1 circuits in a unilateral 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Using extracellular local field potential and whole-cell patch recordings from the contralateral and ipsilateral M1 hemispheres of hemi-parkinsonian rats, we observed a significantly elevated field excitatory postsynaptic potential (fEPSP) input-output function but unchanged intrinsic neuronal excitability in the M1 superficial layer. An altered relative contribution between alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated transmission was reflected by a significantly increased AMPA/NMDA ratio. Markedly reduced inhibitory synaptic tone was also evidenced by the decreased amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), supporting an E-I imbalance favoring excitation in PD. Furthermore, group I metabotropic glutamate receptor (mGluR1/5)-dependent long-term depression (LTD) was abolished in the ipsilateral PD hemisphere, whereas NMDAR-dependent LTD remained intact. In summary, dopamine depletion appears to enhance network excitation and disrupt mGluR1/5-mediated control of M1 surface circuitry. Our findings identify altered cortical surface mGluR-dependent plasticity in the hemi-parkinsonian model; however, the relationship between these electrophysiological alterations and individual motor outcomes remains to be determined.

Animals↗

PubMed1979

Premature onset of labor, neonatal patent ductus arteriosus, and prostaglandin synthetase antagonists--a rat model of a human problem.

Premature labor and patent ductus arteriosus are two potentially fatal hazards of the human newborn infant. Prostaglandin synthetase antagonists have thus been used to suppress early labor and to close the ductus of the neonate. Indomethacin has been most effective but not free of significant complications. Neuronal necrosis may result from numerous systemic aberrations. A controlled rat model study was therefore devised to investigate fetal neuronal necrosis in relation to maternal indomethacin dose. Dams were given various treatments of 2 mg/kg of 4 mg/kg indomethacin within the last 3 days of gestation. Liquid chromatography was used to assess serum maternal and fetal drug levels. From light microscopy of more than 200 brains it was apparent that fetal neuronal necrosis correlates with maternal dose.

Animals↗

PubMed2026

The Anti-Osteoporosis Effects of Panax japonicus via Downregulation of Inflammatory Factors: A Network Pharmacology and Ovariectomized Rat Model Study.

OBJECTIVE: Osteoporosis is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Panax japonicus has been clinically used in the treatment of bone diseases, especially osteoporosis. However, there is a lack of study on the mechanism of osteoporosis treatment with Panax japonicus. MATERIALS AND METHODS: A network pharmacology approach was employed to identify the targets of osteoporosis and Panax japonicus. Cytoscape 3.7.2 and DAVID were used to visualize the pharmacological mechanism of Panax japonicus in treating osteoporosis by building up compound-target and protein-protein interaction (PPI) networks and conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. An ovariectomized SD rat osteoporosis model was used to assess the potential therapeutic effect of Panax japonicus in vivo. The biomechanical properties, pathological changes, inflammatory cytokines, bone density, and bone microstructural parameters in rat bone tissue were carefully measured. The biochemical markers of bone metabolism in serum were detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS AND DISCUSSION: Fifty-two active components and sixty-five target genes of Panax japonicus involved in the treatment of osteoporosis were identified. The PPI network revealed IL-6, TNF, NR3C1, IL-1β, CASP3, ESR1, PGR, and AR to be involved in the treatment of osteoporosis with Panax japonicus. Chikusetsusaponin IVa and Radix ginsenoside-Ro were the main saponins found in Panax japonicus. Panax japonicus was found to exert potent preventive effects on osteoporosis by maintaining biomechanical properties, increasing bone mineral density, and protecting the trabecular microstructure in an ovariectomized rat osteoporosis model. Panax japonicus hindered the initiation of osteoporosis induced by ovariectomy by regulating bone metabolism and downregulating the expression of IL-6 and TNF-α. CONCLUSION: Panax japonicus was found to contain 52 compounds and 65 targets in the treatment of osteoporosis. The administration of Panax japonicus could mitigate osteoporosis in rats induced by ovariectomy, and one of the mechanisms was associated with downregulating the expression of inflammatory factors.

Animals↗