scholarly journals How does intraarticular dexmedetomidine injection effect articular cartilage and synovium? An animal study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Başak Akça ◽  
Aysun Ankay Yılbaş ◽  
Filiz Üzümcügil ◽  
Berkem Büyükakkuş ◽  
Elham Bahador Zırh ◽  
...  
Keyword(s):  
Pain Relief ◽  
Knee Joint ◽  
Animal Study ◽  
Left Knee ◽  
Control Group ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Arthroscopic Knee ◽  
The Right

Abstract Background Intraarticular injections are widely used to provide pain relief after arthroscopic procedures and minimize the use of opioids. Dexmedetomidine has been proven to potentiate pain relief and postpone the demand for the first analgesic drug when it is used intraarticularly following arthroscopic knee procedures. However, the effects of dexmedetomidine on articular structures have not yet been evaluated. Our aim was to determine the effects of intraarticular dexmedetomidine injection on articular structures such as cartilage and synovium. Design Animal study. Methods Twenty adult rats (Sprague-Dawley) were enrolled in the study. Following appropriate aseptic and anesthetic conditions, dexmedetomidine (100 mcg/ml) (0.25 ml) was injected into the right knee joint (the study group) and normal saline solution (0.25 ml) into the left knee joint (the control group) of the rats. Four rats were sacrificed from each group on days 1, 2, 7, 14, and 21, and knee joint samples were obtained. Histologists evaluated the articular and periarticular regions and the synovium using histological sections, and a five-point scale was used to grade the inflammatory changes in a blinded manner. Results The groups were found to be similar in terms of median congestion scores, edema and inflammation scores, subintimal fibrosis, neutrophil activation and cartilage structure at each of the time intervals. Conclusion In our placebo-controlled, in vivo trial, the intraarticular use of dexmedetomidine seemed to be safe with respect to the studied histopathological parameters. However, complementary studies investigating the histopathological effects, analgesic dosage and adverse effects of dexmedetomidine on damaged articular structure models are needed.

scholarly journals Intra-articular Adenosine, Lidocaine and Magnesium (ALM) solution decreases postoperative joint fibrosis in an experimental knee implant model

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jodie L. Morris ◽  
Hayley L. Letson ◽  
Peter McEwen ◽  
Erik Biros ◽  
Constantin Dlaska ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Expression Profiles ◽  
Left Knee ◽  
Joint Capsule ◽  
Infrapatellar Fat Pad ◽  
Control Group ◽  
Sprague Dawley ◽  
Implant Surgery ◽  
Replacement Surgery ◽  
The Right

Abstract Background There is currently no drug therapy to prevent arthrofibrosis following knee surgery. We aimed to determine if the anti-ischemic and anti-inflammatory drug adenosine, lidocaine and Mg2+ (ALM), reduces surgery-related arthrofibrosis in a rat model of knee implant surgery. Methods Male Sprague-Dawley rats (n = 24) were randomly divided into ALM or saline groups. The right knee of each animal was implanted with custom titanium (femur) and polyethylene (tibia) implants, and the left knee served as a non-operated control. An intra-articular ALM or saline bolus (0.1 ml) was administered at the end of surgery, and animals monitored for 4 weeks. Fibrotic changes were assessed by macroscopic examination, histopathology, and expression of key inflammatory and fibrotic markers in the joint capsule and infrapatellar fat pad (IFP). Results Knee swelling was evident in both groups at 4 weeks. However, range of motion was 2-fold higher in the ALM-treated knees, and differences in macroscopic pathology indicated improved healing, compared to the control group. Histologically, ALM treatment also led to significantly decreased synovitis and fibrotic pathology in the joint capsule and IFP compared to saline controls. RNA and protein expression profiles of pro-fibrotic mediators (α-SMA, TGF-β1, FGF1, PDGFA) were also significantly lower in knees from ALM-treated animals. In addition, the expression of inflammatory mediators was lower in plasma (IL-1β, IL-10) and joint tissue (NFκB, IL-1β, IL-12), 4 weeks after surgery. Conclusion We show that intra-articular administration of a single ALM bolus significantly decreased fibrotic pathology and synovitis in an experimental model of knee implant surgery, by blunting inflammation and modulating essential genes of fibrosis. ALM has the therapeutic potential for translation into humans undergoing knee replacement surgery.

scholarly journals 7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection

2021 ◽  
Vol 22 (21) ◽  
pp. 11815
Author(s):  
Alejandro Gallego-Ortega ◽  
Beatriz Vidal-Villegas ◽  
María Norte-Muñoz ◽  
Manuel Salinas-Navarro ◽  
Marcelino Avilés-Trigueros ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ex Vivo ◽  
Control Group ◽  
Nerve Transection ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Adult Rats ◽  
Mixed Response ◽  
Optic Nerve Transection

To analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) (n = 24) and the other (n = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group (n = 6). Treated rats were analyzed 7 (n = 14), 14 (n = 14) or 21 d (n = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a+), α-like (OPN+), α-OFF like (OPN+Brn3a+) or M4-like/α-ON sustained RGCs (OPN+Tbr+). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs decreased to less than one half and OPN+Brn3a+RGCs decreased to approximately 0.5%, and Brn3a+RGCs showed a progressive loss with time, while OPN+RGCs and OPN+Tbr2+RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPN+RGCs and OPN+Tbr2+RGCs for up to 14 d and of Brn3a+RGCs for up to 21 days. DHF affords significant rescue of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs, but not OPN+Brn3a+RGCs, and preserves functional ERG responses after IONT.

Recovery periods restore mechanosensitivity to dynamically loaded bone

2001 ◽  
Vol 204 (19) ◽  
pp. 3389-3399 ◽  
Author(s):  
Alexander G. Robling ◽  
David B. Burr ◽  
Charles H. Turner
Keyword(s):  
Bone Formation ◽  
Bone Cells ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Four Point Bending ◽  
Rat Tibia ◽  
Time Required ◽  
The Right

SUMMARY Bone cells are capable of sensing and responding to mechanical forces, but mechanosensitivity begins to decline soon after the stimulus is initiated. Under continued stimulation, bone is desensitized to mechanical stimuli. We sought to determine the amount of time required to restore mechanosensitivity to desensitized bone cells in vivo by manipulating the recovery time (0, 0.5, 1, 2, 4 or 8 h) allowed between four identical daily loading bouts. We also investigated the osteogenic effectiveness of shorter-term recovery periods, lasting several seconds (0.5, 3.5, 7 or 14 s), introduced between each of 36 identical daily loading cycles. Using the rat tibia four-point bending model, the right tibia of 144 adult female Sprague-Dawley rats was subjected to bending, sham bending or no loading. In the rats receiving recovery periods between loading bouts, histomorphometric measurements from the endocortical surface of the loaded and nonloaded control (left) tibiae revealed more than 100 % higher relative bone formation rates in the 8 h recovery group than in the 0 and 0.5 h recovery groups. Approximately 8 h of recovery was sufficient to restore full mechanosensitivity to the cells. In the rats allowed time to recover between load cycles, 14 s of recovery resulted in significantly higher (66–190 %) relative bone formation rates compared to any of the three shorter recovery periods. In both experiments, bone formation in the sham-bending animals was similar to that in the nonloaded control group. The results demonstrate the importance of recovery periods for (i) restoring mechanosensitivity to bone cells and (ii) maximizing the osteogenic effects of mechanical loading (exercise) regimens.

scholarly journals Functional Evaluation of a Novel Multi-Axial Alveolar Distractor—Preliminary In Vivo Animal Study

2021 ◽  
Vol 11 (4) ◽  
pp. 1898
Author(s):  
Cheng-Hsien Wu ◽  
Kun-Chun Chen ◽  
Yang-Sung Lin ◽  
Yuan-Chih Liu ◽  
Chun-Li Lin
Keyword(s):  
Mechanical Strength ◽  
Animal Study ◽  
Bone Growth ◽  
Alveolar Bone ◽  
Control Group ◽  
Functional Evaluation ◽  
Intact Bone ◽  
Living Bone ◽  
The Right

This study evaluates the biomechanical performance of a new multi-axial alveolar distractor using an animal study. The multi-axial alveolar distractor is designed with a ball and socket joint mechanism that can rotate up to 60° toward the buccal/lingual and mesial/distal sides intra-operatively to achieve vector control. The transport segment can be moved through activating the transport screw with 0.25 pitch, allowing 13 mm in distraction height. This distractor was fixed at the right angulus mandibular of experimental rabbits and adjusted 15° toward the mesial side and 25° toward the buccal side as Group TMB (toward mesial-buccal) (n = 3), and 15° toward the mesial side as Group TM (toward mesial) (n = 3). Group TC (control) was the control group. The distractors were activated 1 mm/day for 13 days. Living bone growth was observed at various periods. The total bone growth length at the angulus region and buccal side distraction thickness after distraction were calculated. The variations in bone growth geometric shape at the mandible angulus were also recorded. Fracture testing was performed to understand the variations in the mechanical strength between the distracted and intact bone specimens. The digital radiography results showed that the osteotomy areas at the mandible angulus were healed and the bone growth completed after surgery. The average bone growth length of Group TMB was 17.68 mm. This was greater than that of Group TM at 14.79 mm. The corresponding buccal side distractor thicknesses for Group TMB and TM after distraction were 5.12 ± 0.52 mm and 3.32 ± 0.37 mm, respectively. The tensile strengths of the bone specimens after distraction of Groups TMB, TM and TC were 172.13 N, 119.27 N and 304.24 N, respectively, and the percentage of distraction bone tensile strength to normal bone was 57% and 39% for Groups TMB and TM, respectively. This study concluded that this new multi-axial alveolar bone distractor can drive bones to grow in accordance with the direction/angle of the distraction plan. The bone growth healed gradually and presented insufficient mechanical strength.

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

scholarly journals The role of intra-articular neuronal CCR2 receptors in knee joint pain associated with experimental osteoarthritis in mice

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shingo Ishihara ◽  
Alia M. Obeidat ◽  
David L. Wokosin ◽  
Dongjun Ren ◽  
Richard J. Miller ◽  
...  
Keyword(s):  
Knee Joint ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Direct Stimulation ◽  
Sensory Afferents ◽  
Neuronal Marker ◽  
The Right ◽  
Experimental Osteoarthritis ◽  
In Vivo Calcium Imaging

Abstract Background C–C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model. Methods DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2RFP C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca2+ imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2RFP mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents. Results WT, but not Ccr2 null, mice displayed knee hyperalgesia 2–16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM. Conclusions The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.

Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat

1998 ◽  
Vol 275 (5) ◽  
pp. R1468-R1477 ◽  
Author(s):  
Scott K. Powers ◽  
Haydar A. Demirel ◽  
Heather K. Vincent ◽  
Jeff S. Coombes ◽  
Hisashi Naito ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Control Group ◽  
Sprague Dawley ◽  
Endurance Exercise Training ◽  
Nonprotein Thiols

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher ( P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant ( P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels ( P < 0.05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.

scholarly journals Dose-dependent effect of betamethasone on the articular cartilage (experimental study)

2021 ◽  
Vol 27 (1) ◽  
pp. 80-86
Author(s):  
A.N. Nuriakhmetov ◽  
◽  
I.F. Akhtiamov ◽  
D.E. Tsyplakov ◽  
A.M. Abdullah ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Inflammatory Cell ◽  
Left Knee ◽  
Knee Joints ◽  
Control Group ◽  
Rabbit Knee ◽  
Frequency Of Use ◽  
The Right ◽  
Dose Dependent ◽  
Dose Dependent Effect

Introduction Glucocorticosteroid injections have been widely used in clinical practice. Betamethasone is one of the agents of this group of drugs. Its efficacy and therapeutic effect with intra-articular administration are undeniable. There are special instructions on the dosage and frequency of use of the drug but unfortunately there are cases of its wrong administration. There is also an evidence of an adverse effect on cartilage both of the drug itself and its combination with local anesthetics. Aim Evaluation of the results of different weekly intra-articular protocols of betamethasone administration on histological preparations of rabbit knee joints. Methods Histological preparations of the right knee joints of three groups of rabbits were studied: after one, three, and six administrations of betamethason per week and the control intact left knee joints. Results Histological preparations of the control group and the group with a single weekly administration of the drug did not have any changes in the structure of diarthrosis. Dystrophic and necrotic changes affecting all morphological components were observed in the joints of animals that received intra-articular injections of betamethason three times a week (compared to a single injection, the area of dystrophy and necrosis of the cartilage was greater by 10.05 ± 0.75 % (p < 0.05), of subchondral bone by 8.11 ± 0.5 % (p < 0.001), and of synovium by 6.25 ± 0.32 % (p < 0.05). The group with six injections of the drug per week had the most pronounced changes. The area of necrotic changes of the cartilage was greater by 6.39 ± 0.75 % than in the group with three injections per week (p < 0.001), of subchondral bone by 11.18 ± 0.5 % (p < 0.001), of synovium by 6.12 ± 0.32 % (p < 0.001). Discussion Inflammatory cell infiltration of joint structures was absent in all cases. It indicates an aseptic nature of tissue necrosis. Evidence has been obtained between the increase in the frequency of intra-articular injections of betamethasone and the severity of dystrophic and necrotic changes in all morphological components of the joint.

Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats

1999 ◽  
Vol 276 (3) ◽  
pp. E558-E564 ◽  
Author(s):  
Regine Minet-Quinard ◽  
Christophe Moinard ◽  
Françoise Villie ◽  
Stephane Walrand ◽  
Marie-Paule Vasson ◽  
...  
Keyword(s):  
Control Group ◽  
Synthetase Activity ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Glucocorticoid Treatment ◽  
Sprague Dawley Rats ◽  
End Of Treatment ◽  
Catabolic State ◽  
Old Rats

Aged rats are more sensitive to injury, possibly through an impairment of nitrogen and glutamine (Gln) metabolisms mediated by glucocorticoids. We studied the metabolic kinetic response of adult and old rats during glucocorticoid treatment. The male Sprague-Dawley rats were 24 or 3 mo old. Both adult and old rats were divided into 7 groups. Groups labeled G3, G5, and G7 received, by intraperitoneal injection, 1.50 mg/kg of dexamethasone (Dex) for 3, 5, and 7 days, respectively. Groups labeled G3PF, G5PF, and G7PF were pair fed to the G3, G5, or G7 groups and were injected with an isovolumic solution of NaCl. One control group comprised healthy rats fed ad libitum. The response to aggression induced specifically by Dex (i.e., allowing for variations in pair-fed controls) appeared later in the aged rats (decrease in nitrogen balance from day 1 in adults but only from day 4 in old rats). The adult rats rapidly adapted to Dex treatment, whereas the catabolic state worsened until the end of treatment in the old rats. Gln homeostasis was not maintained in the aged rats; despite an early increase in muscular Gln synthetase activity, the Gln pool was depleted. These results suggest a kinetic impairment of both nitrogen and muscle Gln metabolisms in response to Dex with aging.

scholarly journals Synergistic toxicity in an in vivo model of neurodegeneration through the co-expression of human TDP-43M337V and tauT175D protein

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Alexander J. Moszczynski ◽  
Madeline Harvey ◽  
Niveen Fulcher ◽  
Cleusa de Oliveira ◽  
Patrick McCunn ◽  
...  
Keyword(s):  
Tau Protein ◽  
Sensorimotor Gating ◽  
In Vivo Model ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Tau Pathology ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Somatic Gene Transfer

Abstract Although it has been suggested that the co-expression of multiple pathological proteins associated with neurodegeneration may act synergistically to induce more widespread neuropathology, experimental evidence of this is sparse. We have previously shown that the expression of Thr175Asp-tau (tauT175D) using somatic gene transfer with a stereotaxically-injected recombinant adeno-associated virus (rAAV9) vector induces tau pathology in rat hippocampus. In this study, we have examined whether the co-expression of human tauT175D with mutant human TDP-43 (TDP-43M337V) will act synergistically. Transgenic female Sprague-Dawley rats that inducibly express mutant human TDP-43M337V using the choline acetyltransferase (ChAT) tetracycline response element (TRE) driver with activity modulating tetracycline-controlled transactivator (tTA) were utilized in these studies. Adult rats were injected with GFP-tagged tau protein constructs in a rAAV9 vector through bilateral stereotaxic injection into the hippocampus. Injected tau constructs were: wild-type GFP-tagged 2N4R human tau (tauWT; n = 8), GFP-tagged tauT175D 2N4R human tau (tauT175D, pseudophosphorylated, toxic variant, n = 8), and GFP (control, n = 8). Six months post-injection, mutant TDP-43M337V expression was induced for 30 days. Behaviour testing identified motor deficits within 3 weeks after TDP-43 expression irrespective of tau expression, though social behaviour and sensorimotor gating remained unchanged. Increased tau pathology was observed in the hippocampus of both tauWT and tauT175D expressing rats and tauT175D pathology was increased in the presence of cholinergic neuronal expression of human TDP-43M337V. These data indicate that co-expression of pathological TDP-43 and tau protein exacerbate the pathology associated with either individual protein.

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