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1.
PLoS One ; 15(2): e0228872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069321

RESUMO

This study has investigated the immediate effect of induced hindlimb length difference on hindlimb lameness measured as differences in minimum (Pmin) and maximum (Pmax) pelvic heights in 16 horses trotting in a straight line and lungeing on both hard and soft surfaces with body-mounted inertial sensors. Hindlimb length differences were induced by applying an Easyboot Glue-on shoe to one hindlimb. Changes in Pmin and Pmax with induced hindlimb length difference were assessed with a two-way repeated-measures ANOVA with trial (straight, lunge with inside limb elevation, lunge with outside limb elevation) and surface (hard, soft) as within-subject factors. Change in Pmin, indicating an impact-type lameness, in the hind limb with the elevation, was significant in both the straight line and while lunging on both hard and soft surfaces. Change in Pmax, indicating pushoff-type lameness, in the opposite, non-elevated hind limb, was significant when trotting in a straight line but not while lunging.


Assuntos
Membro Posterior/patologia , Doenças dos Cavalos/diagnóstico , Coxeadura Animal/diagnóstico , Animais , Fenômenos Biomecânicos , Feminino , Marcha/fisiologia , Análise da Marcha/métodos , Análise da Marcha/veterinária , Membro Posterior/fisiopatologia , Doenças dos Cavalos/patologia , Doenças dos Cavalos/fisiopatologia , Cavalos , Coxeadura Animal/patologia , Coxeadura Animal/fisiopatologia , Masculino , Movimento/fisiologia , Pelve/fisiopatologia
2.
J Knee Surg ; 33(1): 15-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30562834

RESUMO

This study aimed to develop a rabbit model of knee contracture in extension and investigate the natural history of motion loss and time-dependent changes in the joint capsule after immobilization. We immobilized the unilateral knee joints of 32 rabbits by maintaining the knee joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of joint contracture by measuring the joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor ß1 (TGF-ß1) in the anterior and posterior joint capsules. After 2 weeks of joint immobilization, the knee joint range of motion was limited, the synovial membrane of the suprapatellar and posterior joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-ß1 were elevated in the anterior and posterior joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior joint capsules after joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-ß1 may be related to joint capsule fibrosis and may be one of the causes of joint contracture.


Assuntos
Fibrose/patologia , Elevação dos Membros Posteriores/efeitos adversos , Membro Posterior/patologia , Imobilização/efeitos adversos , Cápsula Articular/patologia , Fator de Crescimento Transformador beta1/análise , Animais , Artrometria Articular , Moldes Cirúrgicos/efeitos adversos , Colágeno/biossíntese , Contratura/etiologia , Contratura/metabolismo , Contratura/patologia , Modelos Animais de Doenças , Progressão da Doença , Fibrose/etiologia , Fibrose/metabolismo , Membro Posterior/metabolismo , Membro Posterior/fisiopatologia , Imobilização/métodos , Cápsula Articular/química , Cápsula Articular/metabolismo , Masculino , RNA Mensageiro/análise , Coelhos , Amplitude de Movimento Articular , Membrana Sinovial/química , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
3.
Schweiz Arch Tierheilkd ; 161(10): 677-688, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31586930

RESUMO

INTRODUCTION: Contracture of the flexor tendons (CFT) is very common in calves and it is usually diagnosed within the first few days after birth (congenital flexural deformity). However, CFT can appear even in older calves caused by chronic pain. The aetiology of CFT is still unknown. In this study, the distribution of sex, age, breed, the severity of flexural deformity, concurrent presence of other diseases, applied treatment methods for flexural deformity, and the outcome of calves with CFT, which were examined at the University Clinic for Ruminants in Vienna from 2001 to 2016, were evaluated retrospectively. 93 calves were admitted with CFT in the observation period. 70 (75.3%) calves were male and 78 (83.9%) of the affected animals were Simmental calves. The age of calves with CFT varied from one day to 41 days. Twenty-six calves suffered exclusively from CFT, and CFT was diagnosed as an additional finding in 67 calves. 91 animals (97.8%) showed CFT on the front limbs, 79 of them (84.9%) on both front limbs. The distribution of the severity scores was as follows: 69 calves (74.2%) had score 1, 17 calves (18.3%) had score 2, three calves (3.2%) had score 3. Three additional calves (3.2%) had a score 1 CFT on one front limb and a score 2 CFT on the other front limb, and one additional calf showed all three scores on both front limbs and one hind limb. 69 patients (74.2%) could be discharged with a significant improvement in CFT after treatment and 24 calves (25.8%) had to be euthanized due to other severe diseases. The results of the applied pedigree analysis do not show that a single gene mutation is the cause for the development of CFT, but rather a complex hereditary pattern has to be assumed. Depending on the severity of CFT and the presence of other concurrent diseases, an early and consistent therapy has to be carried out to achieve the highest possible success. Since animals with CFT are usually restricted in their movement, sufficient colostrum intake must be ensured within the first hours of life.


Assuntos
Doenças dos Bovinos , Doenças Musculoesqueléticas , Animais , Animais Recém-Nascidos , Bovinos , Doenças dos Bovinos/genética , Doenças dos Bovinos/fisiopatologia , Doenças dos Bovinos/terapia , Feminino , Membro Anterior/fisiopatologia , Membro Posterior/fisiopatologia , Masculino , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/fisiopatologia , Doenças Musculoesqueléticas/terapia , Doenças Musculoesqueléticas/veterinária , Linhagem , Estudos Retrospectivos
4.
Stroke ; 50(9): 2531-2538, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31390970

RESUMO

Background and Purpose- Lacunar strokes are subcortical infarcts with small size and high disability rates, largely due to injury of the corticospinal tract in the internal capsule (IC). Current rodent models of lacunar infarcts are created based on stereotactic coordinates. We tested the hypothesis that better understanding of the somatotopy of the IC and guiding the lesion with electrical stimulation would allow a more accurate lesion to the forelimb axons of the IC. Methods- We performed electrophysiological motor mapping and viral tracing to define the somatotopy of the IC of Sprague Dawley rats. For the lesion, we used an optrode, which contains an electrode to localize forelimb responses and an optical fiber to deliver light. The infarct was induced when light activated the photothrombotic agent Rose Bengal, which was administered systemically. Results- We found largely a separate distribution of the forelimb and hindlimb axons in the IC, both by microstimulation mapping and tract tracing. Microstimulation-guided IC lesions ablated the forelimb axons of the IC in rats and caused lasting forelimb impairments while largely preserving the hindlimb axons of the IC and surrounding gray matter. Conclusions- Stimulation guidance enabled selective and reproducible infarcts of the forelimb axons of the IC in rats. Visual Overview- An online visual overview is available for this article.


Assuntos
Axônios/fisiologia , Estimulação Elétrica , Infarto/fisiopatologia , Cápsula Interna/cirurgia , Acidente Vascular Cerebral/cirurgia , Animais , Axônios/patologia , Modelos Animais de Doenças , Feminino , Membro Anterior/fisiopatologia , Membro Anterior/cirurgia , Membro Posterior/patologia , Membro Posterior/fisiopatologia , Cápsula Interna/fisiopatologia , Atividade Motora/fisiologia , Córtex Motor/fisiopatologia , Córtex Motor/cirurgia , Tratos Piramidais/fisiopatologia , Tratos Piramidais/cirurgia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia
5.
IEEE Int Conf Rehabil Robot ; 2019: 429-434, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31374667

RESUMO

In an attempt to promote greater functional recovery after spinal cord injury, researchers have begun exploring combinatorial treatments, such as robotic rehabilitation combined with stem cell transplantation. Since these treatment methods are in their nascent stages, rodent models have been proposed for initial investigations. Robots have been built for locomotion rehabilitation and planar forelimb reach and grasp assessment with rodents; however, a robotic platform suitable for three-dimensional movement rehabilitation of the rodent forelimb has not yet been developed. In this paper, a novel three degree of freedom robotic manipulator for automated forelimb rehabilitation combined with stem cell transplantation after cervical spinal cord injury with rats is proposed. The robot interfaces with a rat in an end-effector manner, measuring and interacting with the forelimb in the 3D Cartesian space. In this work, we trained two rats through behavioral shaping to actively interact with the device during two robot control modes. This work provides preliminary investigations into the feasibility of 3D forelimb rehabilitation with rats, which could be translated as a paradigm for combinatorial treatments after spinal cord injury in a controlled manner.


Assuntos
Membro Posterior/fisiopatologia , Locomoção , Recuperação de Função Fisiológica , Robótica , Traumatismos da Medula Espinal/reabilitação , Animais , Ratos
6.
Arthritis Rheumatol ; 71(12): 2016-2026, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31332965

RESUMO

OBJECTIVE: Arthritis is often characterized by inflammation and bone destruction. This study was undertaken to investigate the contribution of inflammation and bone destruction to pain. METHODS: Inflammation, bone resorption, pain-related behaviors, and molecular markers (activating transcription factor 3 [ATF-3], p-CREB, and transient receptor potential vanilloid channel 1) in sensory neurons were measured in murine glucose-6-phosphate isomerase (G6PI)-induced arthritis, a model of rheumatoid arthritis. Depletion of Treg cells before immunization changed self-limiting arthritis into nonremitting arthritis with pronounced bone destruction. Zoledronic acid (ZA) was administered to reduce bone resorption. RESULTS: Compared to nondepleted mice, Treg cell-depleted mice exhibited arthritis with more severe bone destruction and higher guarding scores (P < 0.05; n = 10 mice per group) as well as more persistent thermal hyperalgesia (P < 0.05), but displayed similar mechanical hyperalgesia at the hindpaws (n = 18-26 mice per group). These pain-related behaviors, as well as an up-regulation of the neuronal injury marker ATF-3 in sensory neurons (studied in 39 mice), appeared before the clinical score (inflammation) became positive and persisted in Treg cell-depleted and nondepleted mice. In the late stage of arthritis, Treg cell-depleted mice treated with ZA showed less bone resorption (<50%; P < 0.01) and less thermal hyperalgesia (P < 0.01) than Treg cell-depleted mice without ZA treatment (n = 15 mice per group), but ZA treatment did not reduce the clinical score and local mechanical hyperalgesia. CONCLUSION: Pain-related behaviors precede and outlast self-limiting arthritis. In nonremitting arthritis with enhanced bone destruction, mainly local thermal, but not local mechanical, hyperalgesia was aggravated. The up-regulation of ATF-3 indicates an early and persisting affection of sensory neurons by G6PI-induced arthritis.


Assuntos
Artrite Experimental/fisiopatologia , Artrite Reumatoide/fisiopatologia , Reabsorção Óssea/fisiopatologia , Dor/imunologia , Fator 3 Ativador da Transcrição/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/imunologia , Reabsorção Óssea/imunologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glucose-6-Fosfato Isomerase , Membro Posterior/fisiopatologia , Hiperalgesia/imunologia , Hiperalgesia/fisiopatologia , Inflamação , Camundongos , Linfócitos T Reguladores/imunologia , Canais de Cátion TRPV/metabolismo , Ácido Zoledrônico/administração & dosagem
7.
Spine (Phila Pa 1976) ; 44(13): E749-E758, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31205164

RESUMO

STUDY DESIGN: A study on shortwave diathermy (SWD) versus no treatment following induced spinal cord injury (SCI) in rats. OBJECTIVE: To investigate the effects of athermal SWD treatment on somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) and hindlimb movements in rats with SCI. SUMMARY OF BACKGROUND DATA: SWD has been proven to improve vascular circulation and reduce inflammation. However, there have been few studies on neuroprotective effect of SWD on SCI. METHODS: Twenty-four female Sprague-Dawley (SD) rats were randomly divided into four groups: sham, SCI, SWD, and intact groups. The SCI model was established using the modified Allen weight-drop method. The SWD group received 15 sessions of athermal SWD treatment over a 3-week period of time at 24 hours after SCI. While the sham group and SCI group received no treatment after surgery. Hindlimb movements were evaluated by the Basso, Beattie, and Bresnahan (BBB) scale before surgery, and on days 1, 7, 14, and 21 after the surgery, respectively. The SEP and MEP measurements were simultaneously performed to detect the responses of neural conduction. RESULTS: The week-by-week BBB scores showed a gradual improvement in the rats of both SCI and SWD groups from the first week to the end of the study; however, the BBB scores of the SWD group were higher than those of the SCI group over the course of 3 weeks. Data from the SEP and MEP measurements showed a significant improvement in the SWD group compared with the SCI group at each time point of observation, with a more prominent increase of amplitude and a more evident reduction of latency. There was a linear correlation between the BBB scores and the latency and amplitude of SEPs or MEPs. CONCLUSION: Athermal SWD treatment might facilitate the recovery of locomotor function and exert neuroprotective effect on the SCI. LEVEL OF EVIDENCE: N/A.


Assuntos
Diatermia/métodos , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Animais , Feminino , Membro Posterior/fisiopatologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/fisiopatologia , Resultado do Tratamento
8.
J Dairy Sci ; 102(7): 6431-6441, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31103292

RESUMO

The modern dairy industry is plagued by a high prevalence of claw horn lesions in cows, which cause lameness, affect well-being, limit milk production, and are responsible for premature removal of cows from the herd. The lateral hind claws are primarily affected, and this has been linked to a relatively higher load being exerted on the lateral claws when cows shift weight from one hind limb to the other. The vertical ground reaction forces and mean and maximum pressures under the claws were measured in 40 nonlame dairy cows before and during a shift in weight from one hind limb to the other, which was accomplished by applying pressure manually to one side of the pelvis. During square standing on firm ground, about two-thirds of the entire hind limb load was exerted on the 2 lateral claws, and the remaining one-third was exerted on the medial claws combined. At the moment of maximum weight shift, the lateral claw of the loaded limb bore almost two-thirds of the entire load of both hind limbs, with the heel zone bearing almost half of the load of both hind limbs. Subsequently, the load of the lateral claw of the contralateral hind limb decreased, as did the load of both medial claws. Thus, the weight redistribution had occurred predominantly between the lateral hind claws. The high load exerted on a lateral hind claw during weight shift and at maximum weight shift is assumed to play a role in the pathogenesis of claw horn lesions, particularly when accentuated by a softened claw horn and hard flooring.


Assuntos
Doenças dos Bovinos/fisiopatologia , Bovinos/crescimento & desenvolvimento , Doenças do Pé/veterinária , Membro Posterior/fisiopatologia , Casco e Garras/lesões , Coxeadura Animal/fisiopatologia , Animais , Peso Corporal , Bovinos/fisiologia , Feminino , Doenças do Pé/fisiopatologia , Marcha , Membro Posterior/lesões , Casco e Garras/fisiopatologia
9.
J Neurophysiol ; 122(2): 585-600, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30943092

RESUMO

The precise location and functional organization of the spinal neuronal locomotor-related networks in adult mammals remain unclear. Our recent neurophysiological findings provided empirical evidence that the rostral lumbar spinal cord segments play a critical role in the initiation and generation of the rhythmic activation patterns necessary for hindlimb locomotion in adult spinal rats. Since added epidural stimulation at the S1 segments significantly enhanced the motor output generated by L2 stimulation, these data also suggested that the sacral spinal cord provides a strong facilitory influence in rhythm initiation and generation. However, whether L2 will initiate hindlimb locomotion in the absence of S1 segments, and whether S1 segments can facilitate locomotion in the absence of L2 segments remain unknown. Herein, adult rats received complete spinal cord transections at T8 and then at either L2 or S1. Rats with spinal cord transections at T8 and S1 remained capable of generating coordinated hindlimb locomotion when receiving epidural stimulation at L2 and when ensembles of locomotor related loadbearing input were present. In contrast, minimal locomotion was observed when S1 stimulation was delivered after spinal cord transections at T8 and L2. Results were similar when the nonspecific serotonergic agonists were administered. These results demonstrate in adult rats that rostral lumbar segments are essential for the regulation of hindlimb locomotor rhythmicity. In addition, the more caudal spinal networks alone cannot control locomotion in the absence of the rostral segments around L2 even when loadbearing rhythmic proprioceptive afferent input is imposed.NEW & NOTEWORTHY The exact location of the spinal neuronal locomotor-related networks in adult mammals remains unknown. The present data demonstrate that when the rostral lumbar spinal segments (~L2) are completely eliminated in thoracic spinal adult rats, hindlimb stepping is not possible with neurochemical modulation of the lumbosacral cord. In contrast, eliminating the sacral cord retains stepping ability. These observations highlight the importance of rostral lumbar segments in generating effective mammalian locomotion.


Assuntos
Comportamento Animal/fisiologia , Geradores de Padrão Central/fisiologia , Eletromiografia/métodos , Potenciais Evocados/fisiologia , Membro Posterior/fisiologia , Locomoção/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiologia , Animais , Fenômenos Biomecânicos , Estimulação Elétrica , Espaço Epidural , Feminino , Membro Posterior/fisiopatologia , Vértebras Lombares , Ratos , Ratos Sprague-Dawley , Sacro , Medula Espinal/fisiopatologia , Vértebras Torácicas
10.
Neural Plast ; 2019: 2098083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984253

RESUMO

Although referred pain or hypersensitivity has been repeatedly reported in irritable bowel syndrome (IBS) patients and experimental colitis rodents, little is known about the neural mechanisms. Spinal long-term potentiation (LTP) of nociceptive synaptic transmission plays a critical role in the development of somatic hyperalgesia in chronic pain conditions. Herein, we sought to determine whether spinal LTP contributes to the referral hyperalgesia in colitis rats and particularly whether electroacupuncture (EA) is effective to alleviate somatic hyperalgesia via suppressing spinal LTP. Rats in the colitis group (induced by colonic infusion of 2,4,6-trinitrobenzenesulfonic acid, TNBS), instead of the control and vehicle groups, displayed evident focal inflammatory destruction of the distal colon accompanied not only with the sensitized visceromotor response (VMR) to noxious colorectal distension (CRD) but also with referral hindpaw hyperalgesia indicated by reduced mechanical and thermal withdrawal latencies. EA at Zusanli (ST36) and Shangjuxu (ST37) attenuated the severity of colonic inflammation, as well as the visceral hypersensitivity and referral hindpaw hyperalgesia in colitis rats. Intriguingly, the threshold of C-fiber-evoked field potentials (CFEFP) was significantly reduced and the spinal LTP was exaggerated in the colitis group, both of which were restored by EA treatment. Taken together, visceral hypersensitivity and referral hindpaw hyperalgesia coexist in TNBS-induced colitis rats, which might be attributed to the enhanced LTP of nociceptive synaptic transmission in the spinal dorsal horn. EA at ST36 and ST37 could relieve visceral hypersensitivity and, in particular, attenuate referral hindpaw hyperalgesia by suppressing the enhanced spinal LTP.


Assuntos
Colite/fisiopatologia , Eletroacupuntura , Hiperalgesia/fisiopatologia , Potenciação de Longa Duração , Nociceptividade/fisiologia , Medula Espinal/fisiopatologia , Animais , Colite/induzido quimicamente , Colite/prevenção & controle , Modelos Animais de Doenças , Membro Posterior/fisiopatologia , Hiperalgesia/complicações , Masculino , Limiar da Dor , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico/administração & dosagem
11.
Mater Sci Eng C Mater Biol Appl ; 99: 322-332, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889706

RESUMO

Vascular disease is a major complication of aging, but the molecular mechanisms underlying the aging-induced vascular dysfunction remain unclear, and there is no effective treatment to prevent aging induced diseases. The objectives of the present study are to identify the signaling pathway mediating aging-induced vascular dysfunction and to develop an exosome based therapy to inhibit aging process. We used 11-month-old C57BL6 mice as pre-aging animal model and H2O2 treated H9C2 cells as an in vitro aging model to examine the therapeutic effect of miR-675. We found decreased expression of the potential aging modulator miR-675 in aging muscle, and H2O2 treatment decreased the expression of miR-675 and upregulated the expression of the aging marker ß-gal and TGF-ß1. We also found that miR-675 mimic decreased ß-gal staining in H2O2 treated H9C2 cells. Dual-luciferase reporter assays verified TGF-ß1 as the target gene of miR-675. Moreover, senescent H9C2 cells incubated with exosomes isolated from UMSCs transfected with the miR-675 mimic showed increased expression of miR-675, reduced activity of the aging marker ß-gal and reduced protein levels of TGF-ß1. We employed silk fibroin hydrogel to encapsulate exosomes in order to prolong the half-life of exosome in vivo. Fourier transform infrared spectroscopy (FTIR) revealed that exosomes were successfully encapsulated by the hydrogel. Laser Doppler perfusion imaging showed that the miR-675 exosomes encapsulated in silk fibroin hydrogel promote blood perfusion in ischemic hindlimbs. We demonstrated that miR-675 exosomes encapsulated in silk fibroin hydrogel provided sustained release of exosomes in vitro, and increased the retention time of red fluorescent PKH26-exosome in the tissue. Taken together, this study identified miR-675 as an important regulator of cell senescence and provided a novel strategy to deliver powerful exosomes by silk fibroin hydrogel to treat aging-induced vascular dysfunction.


Assuntos
Envelhecimento/patologia , Exossomos/metabolismo , Fibroínas/química , Técnicas de Transferência de Genes , Membro Posterior/fisiopatologia , Hidrogéis/química , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Animais , Sequência de Bases , Bombyx , Forma Celular , Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Membro Posterior/irrigação sanguínea , Humanos , Camundongos , MicroRNAs/genética , Perfusão , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Cordão Umbilical/citologia
12.
Am J Physiol Regul Integr Comp Physiol ; 316(5): R417-R426, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840487

RESUMO

Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in anesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 µg/100 ml). We found that the pressor (change in mean arterial pressure) response [41 ± 5 mmHg (n = 15) for STZ and 18 ± 3 mmHg (n = 11) for CTL (P < 0.01)] and cardioaccelerator (change in heart rate) response [18 ± 4 beats/min for STZ (n = 15) and 8 ± 2 beats/min (n = 11) for CTL (P < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 ± 7 mmHg (n = 6) before and 27 ± 9 mmHg (n = 6) after GsMTx-4 (P < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.


Assuntos
Pressão Sanguínea/fisiologia , Diabetes Mellitus Experimental/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Contração Muscular/efeitos dos fármacos , Venenos de Aranha/farmacologia , Animais , Estado de Descerebração/fisiopatologia , Feminino , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Masculino , Contração Muscular/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Condicionamento Físico Animal/fisiologia , Ratos Sprague-Dawley , Reflexo/fisiologia
13.
Endocrinology ; 160(5): 1137-1149, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30830222

RESUMO

There is abundant evidence that low circulating testosterone levels in older men are associated with adverse cardiovascular outcomes; however, the direction of causality is unclear. Although there is burgeoning interest in the potential of androgen therapy in older men, the effect of androgens on cardiovascular regeneration in aging males remains poorly defined. We investigated the role of androgens in age-related impairment in ischemia-induced neovascularization. Castrated young (2 months) and old (24 months) male mice were subjected to unilateral hindlimb ischemia and treated with subdermal DHT or placebo Silastic implants. Blood flow recovery was enhanced by DHT treatment in young and old mice compared with age-matched placebo controls. DHT augmented angiogenesis in young mice and ameliorated age-related impairment in neovascularization in old mice. Administration of DHT was associated with increased hypoxia inducible factor-1α (HIF-1α) and stromal cell‒derived factor-1 expression in young mice, but not in old mice. In vitro, DHT-induced HIF-1α transcriptional activation was attenuated in fibroblasts from old mice. Interaction between androgen receptor (AR) and importins, key proteins that facilitate nuclear translocation of AR, was impaired with age. In contrast, DHT treatment stimulated the production and mobilization of Sca1+/CXCR4+ circulating progenitor cells in both young and old mice. DHT stimulated the migration and proangiogenic paracrine effect of ex vivo cultured bone marrow‒derived angiogenic cells from young and old mice. In conclusion, androgens ameliorated age-related impairment in ischemia-induced neovascularization. Although age-dependent dysfunction in androgen signaling attenuated some androgen effects on angiogenesis, provasculogenic effects of androgens were partially preserved with age.


Assuntos
Envelhecimento/fisiologia , Androgênios/farmacologia , Isquemia/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Fatores Etários , Animais , Células Cultivadas , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Di-Hidrotestosterona/farmacologia , Expressão Gênica/efeitos dos fármacos , Membro Posterior/irrigação sanguínea , Membro Posterior/metabolismo , Membro Posterior/fisiopatologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/fisiologia
14.
Lab Invest ; 99(4): 499-513, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30487596

RESUMO

Rheumatoid arthritis is an autoimmune disease with a poor prognosis. Pyroptosis is a type of proinflammatory programmed cell death that is characterised by the activation of caspase-1 and secretion of the proinflammatory cytokines interleukin (IL)-1ß/18. Previous reports have shown that pyroptosis is closely related to the development of some autoimmune diseases, such as rheumatoid arthritis. The decrease in the pH of joint fluid is a main pathogenic feature of RA and leads to excessive apoptosis in chondrocytes. Acid-sensitive ion channels (ASICs) are extracellular H+-activated cation channels that mainly influence Na+ and Ca2+ permeability. In this study, we investigated the role of Ca2+ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in an adjuvant arthritis rat model. The expression of apoptosis-associated speck-like protein, NLRP3, caspase-1, ASIC 1a, IL-1ß and IL-18 was upregulated in the joints of rats compared with that in normal rats, but the expression of Col2a in cartilage was decreased. However, these changes were reversed by amiloride, which is an inhibitor of ASIC1a. Extracellular acidosis significantly increased the expression of ASIC1a, IL-1ß, IL-18, ASC, NLRP3 and caspase-1 and promoted the release of lactate dehydrogenase. Interestingly, Psalmotoxin-1 (Pctx-1) and BAPTA-AM inhibited these effects. These results indicate that ASIC1a mediates pyroptosis in chondrocytes from AA rats. The underlying mechanism may be associated with the ability of ASIC1a to promote [Ca2+]i and upregulate the expression of the NLRP3 inflammasome.


Assuntos
Canais Iônicos Sensíveis a Ácido/metabolismo , Artrite Experimental/metabolismo , Cálcio/metabolismo , Condrócitos/metabolismo , Piroptose/fisiologia , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/fisiologia , Animais , Cartilagem Articular/citologia , Células Cultivadas , Técnicas de Silenciamento de Genes , Membro Posterior/fisiopatologia , Concentração de Íons de Hidrogênio , Masculino , Ratos , Ratos Sprague-Dawley
15.
Vet Rec ; 184(2): 63, 2019 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-30242083

RESUMO

Visual equine lameness assessment is often unreliable, yet the full understanding of this issue is missing. Here, we investigate visual lameness assessment using near-realistic, three-dimensional horse animations presenting with 0-60 per cent movement asymmetry. Animations were scored at an equine veterinary seminar by attendees with various expertise levels. Results showed that years of experience and exposure to a low, medium or high case load had no significant effect on correct assessment of lame (P>0.149) or sound horses (P≥0.412), with the exception of a significant effect of case load exposure on forelimb lameness assessment at 60 per cent asymmetry (P=0.014). The correct classification of sound horses as sound was significantly (P<0.001) higher for forelimb (average 72 per cent correct) than for hindlimb lameness assessment (average 28 per cent correct): participants often saw hindlimb lameness where there was none. For subtle lameness, errors often resulted from not noticing forelimb lameness and from classifying the incorrect limb as lame for hindlimb lameness. Diagnostic accuracy was at or below chance level for some metrics. Rater confidence was not associated with performance. Visual gait assessment may overall be unlikely to reliably differentiate between sound and mildly lame horses irrespective of an assessor's background.


Assuntos
Marcha/fisiologia , Doenças dos Cavalos/diagnóstico , Coxeadura Animal/diagnóstico , Animais , Competência Clínica/estatística & dados numéricos , Membro Anterior/fisiopatologia , Membro Posterior/fisiopatologia , Cavalos , Humanos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
16.
Mol Neurobiol ; 56(1): 748-760, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29796991

RESUMO

The transplantation of stem cells from human exfoliated deciduous teeth (SHED) has been studied as a possible treatment strategy for spinal cord injuries (SCIs) due to its potential for promoting tissue protection and functional recovery. The aim of the present study was to investigate the effects of the early transplantation of SHED on glial scar formation and astrocytic reaction after an experimental model of SCI. Wistar rats were spinalized using the NYU Impactor. Animals were randomly distributed into three groups: control (naive) (animal with no manipulation); SCI (receiving laminectomy followed by SCI and treated with vehicle), and SHED (SCI rat treated with intraspinal SHED transplantation, 1 h after SCI). In vitro investigation demonstrated that SHED were able to express mesenchymal stem cells, vimentin and S100B markers, related with neural progenitor and glial cells, respectively. The acute SHED transplantation promoted functional recovery, measured as from the first week after spinal cord contusion by Basso, Beattie, and Bresnahan scale. Twenty-four and 48 h after lesion, flow cytometry revealed a spinal cord vimentin+ cells increment in the SHED group. The increase of vimentin+ cells was confirmed by immunofluorescence. Moreover, the bioavailability of astrocytic proteins such as S100B and Kir4.1 shown to be increased in the spinal cord of SHED group, whereas there was a glial scar reduction, as indicated by ELISA and Western blot techniques. The presented results support that SHED act as a neuroprotector agent after transplantation, probably through paracrine signaling to reduce glial scar formation, inducing tissue plasticity and functional recovery.


Assuntos
Astrócitos/patologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Esfoliação de Dente/patologia , Dente Decíduo/citologia , Animais , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Células Cultivadas , Proteína Glial Fibrilar Ácida/metabolismo , Membro Posterior/fisiopatologia , Humanos , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Traumatismos da Medula Espinal/metabolismo , Vimentina/metabolismo
17.
Am J Phys Med Rehabil ; 98(4): 266-274, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30286018

RESUMO

OBJECTIVE: The aim of this study was to evaluate adaptations in soleus and tibialis anterior muscles in a rat model 4 wks after hemorrhagic stroke. DESIGN: Young adult Sprague Dawley rats were randomly assigned to two groups: stroke and control, with eight soleus and eight tibialis anterior muscles per group. Hemorrhagic stroke was induced in the right caudoputamen of the stroke rats. Control rats had no intervention. Neurologic status was evaluated in both groups before stroke and 4 wks after stroke. Muscles were harvested after poststroke neurologic testing. Muscle fiber types and cross-sectional areas were determined in soleus and tibialis anterior using immunohistochemical labeling for myosin heavy chain. RESULTS: No generalized fiber atrophy was found in any of the muscles. Fiber types shifted from faster to slower in the tibialis anterior of the stroke group, but no fiber type shifts occurred in the soleus muscles of stroke animals. CONCLUSIONS: Because slower myosin heavy chain fiber types are associated with weaker contractile force and slower contractile speed, this faster to slower fiber type shift in tibialis anterior muscles may contribute to weaker and slower muscle contraction in this muscle after stroke. This finding may indicate potential therapeutic benefit from treatments known to influence fiber type plasticity.


Assuntos
Adaptação Fisiológica , Membro Posterior/fisiopatologia , Hemorragias Intracranianas/fisiopatologia , Fibras Musculares Esqueléticas/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Modelos Animais de Doenças , Hemorragias Intracranianas/etiologia , Masculino , Contração Muscular , Músculo Esquelético , Cadeias Pesadas de Miosina , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/etiologia
18.
Bone ; 120: 465-475, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30550849

RESUMO

Profound bone loss occurs following spinal cord injury (SCI) resulting in a high incidence of fractures. While likely caused in part by loss of weight-bearing, there is greater bone loss following SCI when compared to that observed in other disuse animal models. Patients with SCI have a protracted inflammatory response, with elevated circulating levels of pro-inflammatory markers. This chronic inflammation could compound the bone loss attributed to disuse and the loss of neural signaling. To assess this, we examined inflammatory markers and bone turnover regulators in osteocytes from rats with a moderate spinal contusion injury (SCI) and intact controls (CON). We counted osteocytes positive for cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17), and interleukin-10 (IL-10)], osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin, 32 days after the spinal contusion. By day 9 post-injury, the majority of SCI rats had recovered significant locomotor function and were bearing weight on their hindlimbs. However, despite weight-bearing, peripheral QCT scans demonstrated lower bone mass due to SCI in the proximal tibia metaphysis compared to CON. SCI animals also had lower cancellous bone volume, lower bone formation rate (BFR), lower osteoid surface (OS), and higher osteoclast surface (Oc.S). Tibial mid-shaft periosteal BFR was also lower after SCI. Immunohistochemical staining of the distal femur bone revealed cancellous osteocytes positive for TNF-α, IL-6, IL-17, and IL-10 were elevated in SCI animals relative to intact controls. Protein expression of RANKL+, OPG+, and sclerostin+ osteocytes was also higher in SCI rats. At the cortical midshaft, osteocyte TNF-α, IL-6, and sclerostin were statistically higher in SCI vs. CON. With regression analysis, inflammatory factors were associated with changes in bone turnover. In conclusion, inflammatory factors as well as altered mechanical loading influence bone turnover following a moderate SCI. Treatments aimed at minimizing fracture risk after SCI may need to target both the chronically altered inflammatory state as well as disuse-induced bone loss.


Assuntos
Inflamação/patologia , Osteócitos/patologia , Traumatismos da Medula Espinal/patologia , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Osso Cortical/patologia , Osso Cortical/fisiopatologia , Modelos Animais de Doenças , Fêmur/patologia , Fêmur/fisiopatologia , Marcadores Genéticos , Membro Posterior/fisiopatologia , Inflamação/complicações , Modelos Lineares , Masculino , Tamanho do Órgão , Osteócitos/metabolismo , Osteogênese , Periósteo/patologia , Periósteo/fisiopatologia , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Tíbia/patologia , Tíbia/fisiopatologia , Suporte de Carga
19.
J Neuroinflammation ; 15(1): 335, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509328

RESUMO

OBJECTIVE: The regulatory role of capsaicin-sensitive peptidergic sensory nerves has been shown in acute inflammation, but little is known about their involvement in T/B-cell driven autoimmune arthritis. This study integratively characterized the function of these nerve endings in the proteoglycan-induced chronic arthritis (PGIA), a translational model of rheumatoid arthritis. METHODS: Peptidergic afferents were defunctionalized by resiniferatoxin (RTX) pretreatment in BALB/c mice, PGIA was induced by repeated antigen challenges. Hind paw volume, arthritis severity, grasping ability and the mechanonociceptive threshold were monitored during the 17-week experiment. Myeloperoxidase activity, vascular leakage and bone turnover were evaluated by in vivo optical imaging. Bone morphology was assessed using micro-CT, the intertarsal small joints were processed for histopathological analysis. RESULTS: Following desensitization of the capsaicin-sensitive afferents, ankle edema, arthritis severity and mechanical hyperalgesia were markedly diminished. Myeloperoxidase activity was lower in the early, but increased in the late phase, whilst plasma leakage and bone turnover were not altered. Desensitized mice displayed similar bone spurs and erosions, but increased trabecular thickness of the tibia and bony ankylosis of the spine. Intertarsal cartilage thickness was not altered in the model, but desensitization increased this parameter in both the non-arthritic and arthritic groups. CONCLUSION: This is the first integrative in vivo functional and morphological characterization of the PGIA mouse model, wherein peptidergic afferents have an important regulatory function. Their overall effect is proinflammatory by increasing acute inflammation, immune cell activity and pain. Meanwhile, their activation decreases spinal ankylosis, arthritis-induced altered trabecularity, and cartilage thickness in small joints.


Assuntos
Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Capsaicina/farmacologia , Proteoglicanas/toxicidade , Fármacos do Sistema Sensorial/farmacologia , Limiar Sensorial/efeitos dos fármacos , Animais , Tornozelo/diagnóstico por imagem , Cartilagem/patologia , Modelos Animais de Doenças , Diterpenos/farmacologia , Feminino , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Neurotoxinas/farmacologia , Peptídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Coluna Vertebral/diagnóstico por imagem
20.
PLoS One ; 13(12): e0209233, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30550550

RESUMO

Intrauterine crowding (IUC) considerably influences postnatal traits in a polytocous species such as the pig. Previously, our group described how IUC affects locomotion during the piglet's first days of life (until 96 h after birth). We noted a reduced motor performance in piglets with a low birth weight and low vitality (L piglets), compared to piglets with a normal birth weight and normal vitality (N piglets), indicating L piglets are unable to produce enough force. Our current study investigates whether this observed force deficit in L piglets is caused by a reduced force generating capacity in the muscles and/or a lower percentage of type II (fast-contracting) fibers. Volume and fiber length of the main extensor muscles of the hind limb were used to estimate the physiological cross-sectional area (PSCA) and hence calculate the maximal isometric force generating capacity (Fiso-max) of the hind limb. To check for developmental differences between the muscles of L and N piglets, Fiso-max was normalized to body weight (BW), thus yielding a dimensionless variable F'iso-max. To check for differences in muscle composition, m. vastus lateralis was stained immunohistochemically in order to determine the percentage of type II fibers through image analysis. Our results indicate that L piglets have a reduced absolute force generating capacity due to a lesser muscle mass, compared to N piglets. However, when normalized to BW L piglets actually show a larger force generating capacity, suggesting their muscles are more voluminous, given their body mass, than those of N piglets. However, no differences between L and N piglets were detected with regard to muscle composition of the m. vastus lateralis. Based on our data, we can say that neither normalized force generating capacity, nor muscle composition (of the m. vastus lateralis) can explain the observed force deficit in L piglets and as such the effect of IUC on locomotor performance.


Assuntos
Aglomeração , Membro Posterior/crescimento & desenvolvimento , Membro Posterior/fisiopatologia , Locomoção/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Índice de Massa Corporal , Feminino , Membro Posterior/patologia , Masculino , Força Muscular , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/fisiologia , Tamanho do Órgão , Gravidez , Sus scrofa
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