We aimed to determine whether 10 days of treadmill exercise can increase skeletal muscle mass and intramuscular concentrations of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE). Forty female Lewis rats were randomly assigned to either EAE sedentary (EAE-Sed), EAE exercise (EAE-Ex), Control sedentary (Con-Sed) and Control exercise (Con-Ex). Exercising animals completed a 10 day forced exercising training program. Hind limb skeletal muscles were excised and weighed with soleus muscle used for BDNF and NGF quantification. Statistical analysis was done using a one-way analysis of variance. Disability was more pronounced in the EAE-Ex group than in the EAE-Sed group. Exercising animals (EAE-Ex and Con-Ex) had significantly greater bilateral EDL, plantaris and gastrocnemius muscle mass compared to their sedentary animals (p=0.01). The EAE-Ex group had significantly higher NGF concentrations (1.98+/-0.3 pg/mg) compared to Con-Ex (0.96+/-0.07 pg/mg, p=0.003) and Con-Sed (1.2+/-0.2 pg/mg, p=0.04) groups. The main effect of exercise represented a significantly lower BDNF concentrations in the soleus of exercising animals compared to sedentary animals (p=0.03). Our study provides preliminary evidence that exercise increases skeletal muscle mass despite the early onset of disability in EAE animals.
- MeSH
- encefalomyelitida autoimunitní experimentální patologie terapie MeSH
- kondiční příprava zvířat metody MeSH
- kosterní svaly růst a vývoj patologie MeSH
- krysa rodu Rattus MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- posuzování pracovní neschopnosti MeSH
- potkani inbrední LEW MeSH
- sedavý životní styl MeSH
- tělesná hmotnost MeSH
- terapie cvičením metody MeSH
- zadní končetina patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mozkový neurotrofický faktor MeSH
- nervový růstový faktor MeSH
Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb.
- MeSH
- cytokiny terapeutické užití MeSH
- fyziologická neovaskularizace účinky léků MeSH
- hepatocytární růstový faktor metabolismus MeSH
- injekce intramuskulární MeSH
- ischemie farmakoterapie MeSH
- králíci MeSH
- kultivační média speciální farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mezenchymální kmenové buňky metabolismus MeSH
- mezibuněčné signální peptidy a proteiny terapeutické užití MeSH
- průtoková cytometrie MeSH
- tuková tkáň metabolismus MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zadní končetina patologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytokiny MeSH
- hepatocytární růstový faktor MeSH
- kultivační média speciální MeSH
- mezibuněčné signální peptidy a proteiny MeSH
- vaskulární endoteliální růstový faktor A MeSH
OBJECTIVE: To study the effect of the stress of chronic food restriction on the development of adjuvant arthritis in Long Evans male rats. METHODS: Four groups of animals were compared: non-treated control (C) and arthritic (AA) rats, both with free access to food and water and two analogous groups with a 40% food restriction, i.e. non-treated (FR) and arthritic (AA-FR) animals. All rats were killed 22 days following the injection of complete Freund's adjuvant. The parameters measured were: serum levels of albumin (ALB), nitrate, glucose, insulin, corticosterone (CORT), prolactin (PRL) and PRL mRNA in the adenopituitaries. In addition the activity of gamma-glutamyl transpeptidase (GGTP) was measured in the spleen. The pain threshold was determined by the tailflick method. The body weight of the animals was recorded on day 0, 3, 7, 11, 15 and 18 of the disease. RESULTS: Arthritis caused swelling of the hind paw (2.37 +/- 0.15 ml vs 1.1 +/- 0.05ml in controls, p < 0.01) which was prevented in the AA-FR group (1.44 +/- 0.13 ml, not significant against controls). Arthritis increased serum NO and reduced ALB levels; both changes were significantly restored in the FR-AA group. Food restriction did not alter the activation of GGTP, or the decrease of PRL mRNA observed in the AA group. Serum CORT was elevated in rats with food restriction (15.49 +/- 2.1 vs. 3.7 +/- 0.87 microg/dL) and remained enhanced to the same extent in AA and FR-AA groups. The tailflick latency prolonged in the AA group was reduced by food restriction. CONCLUSION: These results show that 40% food restriction associated with elevated CORT levels mitigated the inflammatory parameters activated during AA.
- MeSH
- adenohypofýza metabolismus MeSH
- artritida experimentální krev prevence a kontrola psychologie MeSH
- dusičnany krev MeSH
- gama-glutamyltransferasa metabolismus MeSH
- inzulin krev MeSH
- kortikosteron krev MeSH
- krevní glukóza MeSH
- krysa rodu Rattus MeSH
- měření bolesti MeSH
- messenger RNA metabolismus MeSH
- potkani Long-Evans MeSH
- potravinová deprivace * MeSH
- práh bolesti psychologie MeSH
- prolaktin krev genetika MeSH
- psychický stres * MeSH
- sérový albumin analýza MeSH
- sexuální faktory MeSH
- slezina enzymologie MeSH
- tělesná hmotnost fyziologie MeSH
- zadní končetina patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dusičnany MeSH
- gama-glutamyltransferasa MeSH
- inzulin MeSH
- kortikosteron MeSH
- krevní glukóza MeSH
- messenger RNA MeSH
- prolaktin MeSH
- sérový albumin MeSH
The teratogenic effect of all-trans retinoic acid (RA) was tested in the system of congenic and recombinant inbred (RI) strains of the laboratory rat carrying the mutant Lx allele which determines the polydactyly-luxate syndrome. It was demonstrated that the teratogenic effect of RA is influenced by both the genotype at the Lx locus and the modifying genes. The dose of 100 mg/kg administered by gavage on day 11 of pregnancy induced a statistically significant incidence of preaxial polydactyly in hind limbs of LEW/BN, +/Lx foetuses heterozygous in the mutant allele, whereas no specific limb defects were noted in foetuses LEW/BN, +/+ without the mutant allele. In foetuses homozygous in the mutant allele LEW/BN, Lx/Lx and SHR/BXH2, Lx/Lx, RA conversely induced a significant reduction in the number of toes on the preaxial side of hind limbs and a reduction of the zeugopodium, mostly the tibia. Reduction changes were more marked in SHR/BXH2, Lx/Lx foetuses, in which the tibia was entirely missing and sirenomelia was found. The foetuses in this group have in their genetic background a combination of modifiers that are responsible for oligodactyly and tibial hemimelia in the BXH2 strain. On the basis of continuing mapping of the rat genome, the testing of RA in the system of RI and congenic strains will be utilized for identification of so far hypothetical genes involved in morphogenesis.
- MeSH
- genotyp MeSH
- inbreeding MeSH
- končetiny patologie MeSH
- krysa rodu Rattus MeSH
- polydaktylie genetika MeSH
- potkani inbrední BN MeSH
- potkani inbrední LEW MeSH
- potkani inbrední SHR MeSH
- rekombinace genetická * MeSH
- teratogeny farmakologie MeSH
- tretinoin farmakologie MeSH
- zadní končetina účinky léků patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- teratogeny MeSH
- tretinoin MeSH
Recombinant inbred (RI) and congenic strains carrying the polydactyly-luxate syndrome (PLS) provide an experimental model for the analysis of polygenic control of limb development. PLS is determined by a major gene Lx whose phenotypic expression is strongly influenced by the genetic background upon which it operates. The morphometric analysis of the skeleton of front and hind legs has been carried out. The morphotypes of PLS in RI strains exhibit a continuous variability and transgressive variation compared to BN.Lx and SHR.Lx morphotypes, which strongly indicates the polygenic effects on PLS manifestation. Quantitative trait loci (QTL) were searched for through correlation of genetic markers and morphometric traits. The association analysis revealed statistically significant correlations (P < 0.0003) of morphometric traits with two markers on chromosome 4 (Il6 and A2m) associated with the number of front feet and hind feet phalanges, respectively, one marker on chromosome 7 (D7Mit17) associated with the tibia length, and the somatostatin gene on chromosome 11 associated with the number of front feet phalanges. In addition, suggestive associations of morphometric traits with markers on further nine chromosomes have been found (correlation coefficients ranging from 0.5 to 0.6). The verification of all these findings is in progress by means of double congenic strains which, in addition to the Lx gene, carry differential chromosome segments with putative modifiers.
- MeSH
- genetické markery MeSH
- inbreeding MeSH
- končetiny patologie MeSH
- krysa rodu Rattus MeSH
- morfogeneze MeSH
- polydaktylie genetika MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- rekombinace genetická * MeSH
- zadní končetina patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- genetické markery MeSH