Bipedal Rat Research Articles

Establishment of a bipedal rat model of lumbar facet joint osteoarthritis using intraarticular injection of urinary plasminogen activator

BackgroundPrevious studies have demonstrated that by injecting uPA into the lumbar facet joints (LFJ) of normal rats, a rat LFJOA animal model can be successfully established. However, there is no evidence that intraarticular injection of uPA can induce or much serious osteoarthritis in bipedal rats, which biomechanics is much more similar to human than normal rats. To investigate whether intraarticular injection of urinary plasminogen activator (uPA) can induce LFJOA and low back pain symptoms in bipedal rats.MethodsAn experimental study on the construction of a modified animal model of lumbar facet joints osteoarthritis (LFJOA) which biomechanics is similar to human. Sprague–Dawley rats were treated with intraarticular injection of uPA in the L5–L6 facet joints (uPA group, n = 15) or saline (saline group, n = 15). The forelimbs of both two group rats were amputated. Mechanical and thermal hyperalgesia in the ipsilateral hind paws were evaluated using von Frey hairs and a thermoalgesia instrument, respectively. Toluidine blue staining, hematoxylin–eosin staining, and immunohistochemical examination of the LFJ was performed.ResultsThe saline group rats have not demonstrated significant osteoarthritis in rats LFJ after surgery. The uPA group has not been induced significantly higher mechanical and thermal hyperalgesia in comparison with the saline group. But intraarticular injection of uPA in biped rats induced significantly stronger articular cartilage damage, synovitis, and proliferation of synovial cells in the LFJ. Inflammatory factors such as iNOS, IL-1β, and TNF-a were more significantly expressed in bipedal rat injected with uPA (p < 0.05).ConclusionsIntraarticular injection of uPA can induce LFJOA in bipedal rats, while upright posture does not induce osteoarthritis in rats LFJ in the short term.

200 Unbiased Interrogation of Whole Brain Circuits Identifies Neurons That Restore Walking After Spinal Cord Injury

INTRODUCTION: Currently, there is no cure for locomotor deficits after spinal cord injury (SCI). Despite advances in spinal cord modulation with epidural electrical stimulation, there remains a paucity of therapies targeting the brain due to a poor understanding of the brain’s role post-SCI. Recently developed tissue clearing and light sheet imaging techniques have permitted unbiased three-dimensional interrogation of whole brain circuits, which has opened unexplored avenues for SCI-related brain interrogation. METHODS: We established a novel brain interrogation pipeline for SCI by optimizing mouse whole brain clearing, imaging, and atlas registration after a spontaneous recovery lateral hemisection model. We examined both whole brain cell activity and connectivity with the lumbar cord using cFos immunolabelling and virus-mediated projection tracing, respectively, to identify a functionally and anatomically dynamic region correlating with recovery. We interrogated the locomotor role of this region with optogenetics and chemogenetics. In a more clinically relevant rat contusion SCI, we assessed the translatability of deep brain electrical stimulation (DBS) of this region by leveraging an established bipedal robotic interface and rehabilitation paradigm. RESULTS: We unexpectedly uncovered the lateral hypothalamus (LH) to be a functionally and anatomically dynamic region post-SCI correlating with recovery. Optogenetic stimulation of mouse LHVglut2 neurons significantly augmented locomotor function, which required medullary reticular formation (MRF) Vglut2-positive neurons. In line with previously demonstrated sparing of MRF-to-spinal cord projections after contusion SCI, we found that LH DBS in rats post-contusion SCI could acutely robustly augment bipedal rat locomotor function. CONCLUSION: This is the first demonstration of the LH's role in locomotion post-SCI. The LH is a novel DBS target that robustly augmented locomotor function, dependent on LH and brainstem glutamatergic cells.

Estrogen promotes the onset and development of idiopathic scoliosis via disproportionate endochondral ossification of the anterior and posterior column in a bipedal rat model

This study aimed to verify the effects of estrogen on the onset and development of adolescent idiopathic scoliosis and the mechanisms associated with these effects by constructing a pubescent bipedal rat model. Experiments were conducted to investigate whether scoliosis progression was prevented by a Triptorelin treatment. One hundred twenty bipedal rats were divided into female, OVX (ovariectomy), OVX + E2, Triptorelin, sham, and male groups. According to a spinal radiographic analysis, the scoliosis rates and curve severity of the female and OVX + E2 groups were higher than those in the OVX, Triptorelin, and male groups. The measurements obtained from the sagittal plane of thoracic vertebrae CT confirmed a relatively slower growth of the anterior elements and a faster growth of the posterior elements between T11 and T13 in the female and OVX + E2 groups than in the OVX and Triptorelin groups. Histomorphometry and immunohistochemistry revealed a significantly longer hypertrophic zone of the vertebral cartilage growth plates that expressed more type X collagen and less type II collagen in the OVX and Triptorelin groups than in the female and OVX + E2 groups. Ki67 immunostaining confirmed an increase in the proliferation of vertebral growth plate chondrocytes in the OVX group compared with the female and OVX + E2 groups. In conclusion, estrogen obviously increased the incidence of scoliosis and curve severity in pubescent bipedal rats. The underlying mechanism may be a loss of coupling of the endochondral ossification between the anterior and posterior columns. Triptorelin decreased the incidence of scoliosis and curve magnitudes in bipedal female rats.

Effect of axial vertical vibration on degeneration of lumbar intervertebral discs in modified bipedal rats: An in-vivo study.

To assess the effects of axial vibrations on gene expression and lumbar intervertebral disc degeneration invivo. A modified bipedal rat model was established using a brachial plexus rhizotomy approach to imitate human upright posture. The experimental animals were randomly divided into three groups: control, vertical vibration, and whole-body vibration. Gene expression in degeneration of the intervertebral discs was assessed by reverse transcription-quantitative polymerase chain reaction. The expression of aggrecan, Col1α1, Col2α1, and decorin were shown to be up-regulated in 14-week-old rats in the vertical vibration and whole-body vibration groups, whereas biglycan and versican expression was down-regulated in 14-week-old rats of the two experimental groups. Furthermore, biglycan and versican expression levels were shown to be lower in the whole-body vibration group than in the vertical vibration group (P<0.05). This in-vivo study demonstrated that vibrations can influence the expression of anabolic genes. Furthermore, whole-body vibrations seem to have a greater effect in this regard than vertical vibrations. A new method is expected to relieve the low back pain of the patients through our research.

The value of applying a melatonin antagonist (Luzindole) in improving the success rate of the bipedal rat scoliosis model

BackgroundAn ideal animal model has always been the key to research the pathogenesis and treatment of adolescent idiopathic scoliosis (AIS), while available methods have obvious disadvantages. The deficiency of melatonin has been proved relating to AIS. In this research, we intended to apply Luzindole, the melatonin antagonist, in bipedal rat model, for the block of combination of melatonin and its receptor, to inhibit the melatonin effect, and then to understand whether this method can effectively improve the scoliosis rate of bipedal rat model, and investigate the role of melatonin in scoliosis. To investigate the feasibility of improving the success rate of bipedal rat scoliosis model via intraperitoneal injection of melatonin antagonist (Luzindole).MethodsA total of 60 3-weeks-old Sprague-Dawley rats were included in this study, and were divided into 3 groups (A, B and C). Each group included 20 rats. Osteotomy of the bilateral proximal humerus and proximal tailbone was performed in group A and group B; intraperitoneal injection of Luzindole (0.2 mg/kg) was performed in group A and group C. X-rays were taken before the surgery, 1 month after the surgery, 3 months after the surgery, and 6 months after the surgery, to calculate the Cobb’s angle of the spine (>10° was considered scoliosis). The weight of every rat was also measured at the same time. Rats were euthanized 6 months after surgery to determine the calmodulin level in thrombocytes.ResultsThe rate of scoliosis in group A (14/20) was significantly higher than those in group B (6/20) and group C (0/20) (P < 0.05). The differences in the weights of the 3 groups were non-significant; as were differences in the calmodulin level in thrombocytes.ConclusionThe application of the melatonin antagonist of Luzindole can improve the success rate of the bipedal rat scoliosis model. Meanwhile, this study indicates that a decreased melatonin level is not the primary cause of scoliosis, but that it may increase the likelihood and severity of scoliosis.

Prolonged Upright Posture Induces Degenerative Changes in Intervertebral Discs of Rat Cervical Spine

An in vivo study of the cervical intervertebral discs (IVDs) response to upright posture was performed using an amputated bipedal rat model. To investigate the effects of upright posture on IVDs of rat cervical spine. The distinct arrangement of human neck muscle from that of cat and rhesus indicated that in the evolution process, upright posture might have affected cervical spine of human ancestors. However, the effects of upright posture on cervical spine have not been assessed. Forty-one-month-old rats were randomly divided into 5-month-control, 5-month-surgery, 7-month-control, and 7-month surgery group (n = 10 per group). Both forelimbs of 2 surgery group rats were amputated, and those rats were then induced to be upright in the custom-made cages. Two control group rats were kept in regular cages. These rats were respectively killed at the fifth and seventh month after surgery and the IVD samples of lumbar spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples were used for real-time polymerase chain reaction of type II collagen (Col2a1), type X collagen, matrix metalloproteinase 13 (MMP-13), MMP-3, aggre-can, and aggrecanase-2 (ADAMTS-5). Upright posture affects histologic changes of the cervical IVDs such as fissures of anulus fibrosus and decreased height of disc, decreased protein level of Col2a1 at nucleus pulposus and anulus fibrosus, up-regulated MMP-13, MMP-3, ADAMTS-5, and type X collagen mRNA expression, and downregulated mRNA expression of Col2a1 and aggrecan. Upright stance accelerates cervical disc degeneration in rats.

Modified surgical procedures in rat scoliosis model

Objective Bipedal rat is an ideal animal model in researching scoliosis. However, high mortality remained in current surgical procedures leading to a high rate of failure. Methods Fifteen rats were subjected to the operation of denervation in upper limbs and tethering ribs on the right side using 4-0 non-invasive stitch, and the erector muscle of spine was reserved during the operation. One-week mortality was calculated. Results No complications were observed in the surgical procedures, and no rat died during or after the operation. Conclusion Reservation of the erector muscle of spine and tethering ribs on the right side using 4-0 non-invasive stitch can make the mortality of the operation decline to zero. Key words: Scoliosis; Modle,animal; Surgical procedure

An improved operation approach for bipedal rat model construction

To explore an improved operation approach to make up the ethical deficiency of classical bipedal rat model. 20 SD rats were randomly divided into an improved group and a traditional group averagely. Improved group were operated with plexus brachialis nerve amputation, while traditional group with forelimbs amputation close to shoulder joint. Forelimb and shoulder joint movements were observed and electromyography of the peripheral muscles around shoulder joint were recorded to make certain the paralytic scope. Operation duration and axillary artery hurt probability of both the improved and traditional operation were compared to evaluate the operation risk of improved approach. Mean total upright time on 2 d, 1 w, 2 w, 4 w and 6 w post-operation and upright posture on 6 w post-operation were recorded to evaluate the human-upright-posture-simulating effect of bipedal rats operated with improved approach. Compared with classical amputation approach, improved approach exhibited simpler operation procedure, shorter operation duration and lower axillary artery hurt probability. Electromyography revealed that all forelimb muscles and most shoulder-peripheral muscles were denervated, forelimbs of the improved bipedal rats were absolutely paralyzed and shoulder joint reserved only slight abduction function. The mean total upright time of improved bipedal rats was longer than the classical ones after 2 w post-operation, while upright posture showed no difference with classical bipedal rats. The improved operation approach not only simplified operation procedures, but also achieved even better effect than classical amputation operation and exempted bipedal rat model from the ethical shadow.

膝前十字靭帯に対する運動負荷の影響 （第１報） Ｂｉｐｅｄａｌ ｒａｔを用いた実験的研究

The purpose of this study was to investigate the influence of exercise on the anterior cruciate ligament of bipedal rats biomechanically and histologically.Thirty-six female Wistar rats were divided into three groups as follows: (1) Quadripedal rat [QG]; (2) Bipedal rat without exercise [B-E (-) G]; and (3) Bipedal rat with exercise [B-E (+) G].The rats of each group were terminated accordingly at the age of 20 weeks. The femur-anterior cruciate ligament-tibia prepared and arranged from each group were tested to failure on tensile testing machine and the anterior cruciate ligament of a group of rats were observed by light and electron microscopy.All femur-anterior cruciate ligament-tibia's complexes failed in the site of interstitial ligaments. The strength of the anterior cruciate ligament in B-E (+) G showed a significant increase as compared with QG and B-E (-) G. Observed under light microscopically there were no microtear and degradation change in the anterior cruciate ligament of each group, but again observed under electron microscopically the collagen fibril had a cross-sectional diameter of various sizes from 30nm to 110nm in the anterior cruciate ligament of B-E (+) G.

The experimental study of scoliosis in bipedal rat in lathyrism.

Using Wister albino rats, bipedal rats were prepared; to which semicarbazide at a concentration of 0.075%, 0.05% and 0.025% were given as drinking water and the rats were divided into three groups A, B and C according to such concentrations. Osteolathyrism was caused in this way and the relations between doses as well as the dosing period and the progress of scoliosis were examined roentgenologically and histologically and the following conclusions were obtained. 1. The frequency of occurrence of scoliosis was 82% in the bipedal rats and 13% in the quadrupedal rats (level of significance alpha = 0.001% or less). 2. Primordial top vertebrae were located concentratively in the lower 1/3 of thoracic vertebra. 3. In the primordial curve, those cases showing a right side curve accounted for 76%. 4. After termination of administration of semicarbazide, spontaneous improvement took place only in those cases showing scoliosis of less than 40 degrees. 5. In the author's experimental scoliosis, the static and dynamic condition of posture nearly coincided with those of men in clinical studies. 6. Histological changes were especially marked in the cartilage layer on the vertebral epiphyseal line, being quite diversified.