Efficacy of the immediate adipose-derived stromal vascular fraction autograft on functional sensorimotor recovery after spinal cord contusion in rats.

BACKGROUND: Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined. METHOD: Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1ß, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools. RESULTS: Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups. CONCLUSION: Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion.

Activated Human Adipose Tissue Transplantation Promotes Sensorimotor Recovery after Acute Spinal Cord Contusion in Rats.

Traumatic spinal cord injuries (SCIs) often result in sensory, motor, and vegetative function loss below the injury site. Although preclinical results have been promising, significant solutions for SCI patients have not been achieved through translating repair strategies to clinical trials. In this study, we investigated the effective potential of mechanically activated lipoaspirated adipose tissue when transplanted into the epicenter of a thoracic spinal contusion. Male Sprague Dawley rats were divided into three experimental groups: SHAM (uninjured and untreated), NaCl (spinal cord contusion with NaCl application), and AF (spinal cord contusion with transplanted activated human fat). Pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) were measured to assess endogenous inflammation levels 14 days after injury. Sensorimotor recovery was monitored weekly for 12 weeks, and gait and electrophysiological analyses were performed at the end of this observational period. The results indicated that AF reduced endogenous inflammation post-SCI and there was a significant improvement in sensorimotor recovery. Moreover, activated adipose tissue also reinstated the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions. This investigation highlights the efficacy of activated adipose tissue grafting in acute SCI, suggesting it is a promising therapeutic approach for spinal cord repair after traumatic contusion in humans.

Combined effect of trifluoperazine and sodium cromoglycate on reducing acute edema and limiting lasting functional impairments after spinal cord injury in rats.

Edema formation is one of the very first events to occur after spinal cord injury (SCI) leading to an increase of the intrathecal pressure and consequently to serious spinal tissue and functional impairments. Current edema treatments are still symptomatic and/or non-specific. Since edema formation mechanisms are mainly described as vasogenic and cytotoxic, it becomes crucial to understand the interplay between these two subtypes. Acting on key targets to inhibit edema formation may reduce secondary damage and related functional impairments. In this study, we characterize the edema kinetic after T9-10 spinal contusion. We use trifluoperazine (TFP) to block the expression and the functional subcellular localization of aquaporin-4 supposed to be implicated in the cytotoxic edema formation. We also use sodium cromoglycate (SCG) to deactivate mast cell degranulation known to be implicated in the vasogenic edema formation. Our results show a significant reduction of edema after TFP treatment and after TFP-SCG combined treatment compared to control. This reduction is correlated with limited onset of initial sensorimotor impairments particularly after combined treatment. Our results highlight the importance of potential synergetic targets in early edema therapy after SCI as part of tissue sparing strategies.

Edema after CNS Trauma: A Focus on Spinal Cord Injury.

Edema after spinal cord injury (SCI) is one of the first observations after the primary injury and lasts for few days after trauma. It has serious consequences on the affected tissue and can aggravate the initial devastating condition. To date, the mechanisms of the water content increase after SCI are not fully understood. Edema formation results in a combination of interdependent factors related to mechanical damage after the initial trauma progressing, along with the subacute and acute phases of the secondary lesion. These factors include mechanical disruption and subsequent inflammatory permeabilization of the blood spinal cord barrier, increase in the capillary permeability, deregulation in the hydrostatic pressure, electrolyte-imbalanced membranes and water uptake in the cells. Previous research has attempted to characterize edema formation by focusing mainly on brain swelling. The purpose of this review is to summarize the current understanding of the differences in edema formation in the spinal cord and brain, and to highlight the importance of elucidating the specific mechanisms of edema formation after SCI. Additionally, it outlines findings on the spatiotemporal evolution of edema after spinal cord lesion and provides a general overview of prospective treatment strategies by focusing on insights to prevent edema formation after SCI.

Early movement restriction deteriorates motor function and soleus muscle physiology.

Children with low physical activity and interactions with environment experience atypical sensorimotor development and maturation leading to anatomical and functional disorganization of the sensorimotor circuitry and also to enduring altered motor function. Previous data have shown that postnatal movement restriction in rats results in locomotor disturbances, functional disorganization and hyperexcitability of the hind limb representations in the somatosensory and motor cortices, without apparent brain damage. Due to the reciprocal interplay between the nervous system and muscle, it is difficult to determine whether muscle alteration is the cause or the result of the altered sensorimotor behavior (Canu et al., 2019). In the present paper, our objectives were to evaluate the impact of early movement restriction leading to sensorimotor restriction (SMR) during development on the postural soleus muscle and on sensorimotor performance in rats, and to determine whether changes were reversed when typical activity was resumed. Rats were submitted to SMR by hind limb immobilization for 16 h / day from birth to postnatal day 28 (PND28). In situ isometric contractile properties of soleus muscle, fiber cross sectional area (CSA) and myosin heavy chain content (MHC) were studied at PND28 and PND60. In addition, the motor function was evaluated weekly from PND28 to PND60. At PND28, SMR rats presented a severe atrophy of soleus muscle, a decrease in CSA and a force loss. The muscle maturation appeared delayed, with persistence of neonatal forms of MHC. Changes in kinetic properties were moderate or absent. The Hoffmann reflex provided evidence for spinal hyperreflexia and signs of spasticity. Most changes were reversed at PND60, except muscle atrophy. Functional motor tests that require a good limb coordination, i.e. rotarod and locomotion, showed an enduring alteration related to SMR, even after one month of 'typical' activity. On the other hand, paw withdrawal test and grip test were poorly affected by SMR whereas spontaneous locomotor activity increased over time. Our results support the idea that proprioceptive feedback is at least as important as the amount of motor activity to promote a typical development of motor function. A better knowledge of the interplay between hypoactivity, muscle properties and central motor commands may offer therapeutic perspectives for children suffering from neurodevelopmental disorders.

Delayed Injection of a Physically Cross-Linked PNIPAAm-g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery.

Spinal cord injury is a main health issue, leading to multiple functional deficits with major consequences such as motor and sensitive impairment below the lesion. To date, all repair strategies remain ineffective. In line with the experiments showing that implanted hydrogels, immunologically inert biomaterials, from natural or synthetic origins, are promising tools and in order to reduce functional deficits, to increase locomotor recovery, and to reduce spasticity, we injected into the lesion area, 1 week after a severe T10 spinal cord contusion, a thermoresponsive physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer hydrogel. The effect of postinjury intensive rehabilitation training was also studied. A group of male Sprague-Dawley rats receiving the hydrogel was enrolled in an 8 week program of physical activity (15 min/day, 5 days/week) in order to verify if the combination of a treadmill step-training and hydrogel could lead to better outcomes. The data obtained were compared to those obtained in animals with a spinal lesion alone receiving a saline injection with or without performing the same program of physical activity. Furthermore, in order to verify the biocompatibility of our designed biomaterial, an inflammatory reaction (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities and sensorimotor coordination) was assessed from the day of injection, once a week, for 9 weeks. Finally, 9 weeks postinjection, the spinal reflexivity (rate-dependent depression of the H-reflex) was measured. The results indicate that the hydrogel did not induce an additional inflammation. Furthermore, we observed the same significant locomotor improvements in hydrogel-injected animals as in trained saline-injected animals. However, the combination of hydrogel with exercise did not show higher recovery compared to that evaluated by the two strategies independently. Finally, the H-reflex depression recovery was found to be induced by the hydrogel and, albeit to a lesser degree, exercise. However, no recovery was observed when the two strategies were combined. Our results highlight the effectiveness of our copolymer and its high therapeutic potential to preserve/repair the spinal cord after lesion.

Immediate or Delayed Transplantation of a Vein Conduit Filled with Nasal Olfactory Stem Cells Improves Locomotion and Axogenesis in Rats after a Peroneal Nerve Loss of Substance.

Over the recent years, several methods have been experienced to repair injured peripheral nerves. Among investigated strategies, the use of natural or synthetic conduits was validated for clinical application. In this study, we assessed the therapeutic potential of vein guides, transplanted immediately or two weeks after a peroneal nerve injury and filled with olfactory ecto-mesenchymal stem cells (OEMSC). Rats were randomly allocated to five groups. A3 mm peroneal nerve loss was bridged, acutely or chronically, with a 1 cm long femoral vein and with/without OEMSCs. These four groups were compared to unoperated rats (Control group). OEMSCs were purified from male olfactory mucosae and grafted into female hosts. Three months after surgery, nerve repair was analyzed by measuring locomotor function, mechanical muscle properties, muscle mass, axon number, and myelination. We observed that stem cells significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. OEMSCs remained in the nerve and did not migrate in other organs. These results open the way for a phase I/IIa clinical trial based on the autologous engraftment of OEMSCs in patients with a nerve injury, especially those with neglected wounds.

Total Knee Arthroplasty with a Ti6Al4V/PEEK Prosthesis on an Osteoarthritis Rat Model: Behavioral and Neurophysiological Analysis.

Arthroplasty is a surgical procedure to restore the function of the joint of patient suffering from knee osteoarthritis. However, postoperative functional deficits are reported even after a rehabilitation program. In order to determine the origin of functional deficits of patient suffering from knee osteoarthritis and total knee arthroplasty, we developed a rodent model including a chemically-induced-osteoarthritis and designed a knee prosthesis (Ti6Al4V/PEEK) biomechanically and anatomically adapted to rat knee joint. Dynamic Weight-Bearing, gait kinematics, H-reflex from vastus medialis muscle and activities from metabosensitive III and IV afferent fibers in femoral nerve were assessed at 1 and 3 months post-surgery. Results indicate that knee osteoarthritis altered considerably the responses of afferent fibers to their known activators (i.e., lactic acid and potassium chloride) and consequently their ability to modulate the spinal sensorimotor loop, although, paradoxically, motor deficits seemed relatively light. On the contrary, results indicate that, after the total knee arthroplasty, the afferent responses and the sensorimotor function were slightly altered but that motor deficits were more severe. We conclude that neural changes attested by the recovery of the metabosensitive afferent activity and the sensorimotor loop were induced when a total knee replacement was performed and that these changes may disrupt or delay the locomotor recovery.

Motor and sensitive recovery after injection of a physically cross-linked PNIPAAm-g-PEG hydrogel in rat hemisectioned spinal cord.

In line with experiments showing that implanted hydrogels are promising tools, we designed and injected, after a C2 spinal cord hemisection, a thermoresponsive and thermoreversible physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer in order to reduce functional deficits and provide a favorable environment to axotomized axons. Nasal olfactory ecto-mesenchymal stem cells were cultured on the hydrogel in order to verify its biocompatibility. Then, inflammatory reaction (Interleukin-1ß and 6, Tumor Necrosis Factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities, muscle strength and tactile sensitivity) was assessed once a week, during 12 weeks. Finally, at 12 weeks post-injection, spinal reflexivity and ventilatory adjustments were measured, and the presence of glial cells and regenerated axons were determined in the injured area. Our results indicate that cells survived and proliferated on the hydrogel which, itself, did not induce an enhanced inflammation. Furthermore, we observed significant motor and sensitive improvements in hydrogel-injected animals. Hydrogel also induced H-reflex recovery close to control animals but no improved ventilatory adjustment to electrically-evoked isometric contractions. Finally, regrowing axons were visualized within the hydrogel with no glial cells colonization. Our results emphasize the effectiveness of our copolymer and its high therapeutic potential to repair the spinal cord after injury.

Alteration of Metabosensitive Afferent Response With Aging: Exercised versus Non-exercised Rats.

This study was designed to evaluate the effect of aging on the activity of metabosensitive afferent fibers (thin muscle afferents from group III and IV) and to determine if physical activity performed at old age may influence the afferent discharge. Afferents from tibialis anterior and soleus muscles were recorded on non-exercised rats aged of 3, 6, 12, and 20 months and on animals aged of 12 and 20 months performing a daily incremental treadmill exercise protocol during the last 8 weeks preceding the recordings. Metabosensitive afferent fibers were activated with potassium chloride (KCl) and lactic acid (LA) injections into the blood stream or by muscle electrically-induced fatigue (EIF). Results indicated that aging is associated to a decrease in the magnitude of the responses to chemical injections and EIF. Unfortunately, physical activity did not allow restoring the metabosensitive afferents responses. These results indicate an alteration of the thin afferent fibers with aging and should be taken into account regarding the management of muscle fatigue and potential alterations of exercise pressor reflex (EPR) occurring with aging.

Biocompatibility of four common orthopedic biomaterials following neuroelectromyostimulation: An in-vivo study.

Despite the worldwide high prevalence of total joint arthroplasty (TJA), life expectancy of prosthesis remains limited by mechanical and chemical constraint which promote wear debris production, surrounding tissues damage and finally prosthesis loosening. Such results could be amplified by neuro-myoelectrostimulation (NMES; widely used to reduce neuromuscular deficits observed following TJA surgery). It was previously described in an in vivo experiment that interactions between NMES and Ti6Al4V implant are deleterious for both implant and surrounding muscles. The purpose of the present study was to compare the biocompatibility of four common orthopedic biomaterials, two metallic (Ti6Al4V, CrCo) and two nonmetallic (PEEK, Al2 O3 ) alloys, fixed on rat tibial crest in which the surrounding muscles were electrostimulated. Muscle cell death rate was not found significantly increased, with or without electrical stimulation for nonmetallic implants. Contrary to Ti6Al4V alloy, the CrCo implant did not induce destruction of the surrounding muscle. However, cell viability decreased for both metallic alloys when NMES was applied but within a greater significant extent for Ti6Al4V implant. Otherwise, when NMES was applied, implant-to-bone adhesion significantly decreased for Ti6Al4V while no significant difference was found for PEEK, Al2 O3 , and CrCo. Statistical analyses reveal also a lesser adhesion strength for Ti6Al4V compared with CrCo when NMES was applied. Selecting the most suitable material in term of biocompatibility remains a major concern and non-metallic materials seems to be more appropriated in regard to electrical currents used for post TJA care. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1156-1164, 2018.

Effectiveness of Foot Biomechanical Orthoses to Relieve Patients Suffering from Plantar Fasciitis: Is the Reduction of Pain Related to Change in Neural Strategy?

Plantar fasciitis is a cause of chronic pain under the heel and bottom of the foot. One of the treatments to reduce pain consists of using plantar orthoses to address specific imbalances during foot placement or gait. The aim of the present study was to determine if reduction of pain with a treatment based on plantar orthoses is related to changes in reflexes and muscle activity of the muscles of the lower limbs. Ten patients (51.0±3.5 years, 76.0±2.38 kg, 171.9±1.8 cm, 3 women and 7 men) with plantar fasciitis for less than 1 year were followed up during nine weeks. Soleus M, H, and V waves recorded at rest and during voluntary contraction and Root Mean Square-Electromyogram from four leg muscles recorded during walking and static position were analyzed in patients before and 3, 6, and 9 weeks after wearing orthoses. Pain level and gait and posture parameters were also analyzed. Results were compared to five healthy participants exhibiting no pain (30.6±2.1 years, 60.0±3.5 kg, 167.0±3.4 cm, 3 women and 2 men). Results indicated that pain was significantly reduced after 3 weeks. Hmax/Mmax and Hsup/Msup ratios were significantly higher and MHmax/Mmax and MHsup/Msup were significantly lower in healthy participants compared to patients with plantar fasciitis. No difference in the V/Msup ratio was found between groups. Furthermore, all other measured locomotor, stabilometric, and electromyographic parameters remained unchanged throughout the entire protocol. The reduction of pain is not related to change in neural activity suggesting that, after 9 weeks of wearing plantar orthoses, patients are not yet cured and return to physical activity should be delayed.

Effectiveness of Foot Biomechanical Orthoses to Relieve Patients' Knee Pain: Changes in Neural Strategy After 9 Weeks of Treatment.

Knee pain is one of the most common lower leg complaints. It is often treated with plantar orthoses to provide cushioning and correct locomotion, imbalances of the foot, and postural deficits. However, the published scientific data are poor concerning the mechanisms involved in pain reduction after wearing foot orthoses, and, to the best of our knowledge, no trial has investigated the mid-term effectiveness. The aim of the present study was to evaluate the effectiveness of foot orthoses according to sound biomechanical principles in the treatment of knee pain. Attention was mainly focused on changes in the central control strategies. Fifteen subjects were included in the protocol. The patients with knee pain were compared with healthy participants (control group) exhibiting no knee pain. In the patients with knee pain, pain perception, dynamic analysis of the gait, stabilometry, the soleus Hoffmann reflex at rest and during voluntary contraction, and V-wave were measured before and 3, 6, and 9 weeks after wearing orthoses. In the control group (n = 5), the same parameters were recorded at 0, 3, 6, and 9 weeks, but the subjects had not worn orthoses. In the patient group (n = 10), the results indicated that pain had significantly decreased from the third week onward, although the parameters of gait and stabilometry remained unchanged. From the sixth week, the soleus Hoffmann reflex during voluntary contraction wave was significantly reduced, suggesting an increase in motoneuronal presynaptic inhibition by non-nociceptive afferents. The V-wave amplitude increased throughout the 9 weeks of the experiment, suggesting a progressive increase in corticospinal and/or extrapyramidal descending pathway inputs, probably due to pain reduction. In the control group, no change was observed throughout the experimental sessions. Our data indicated that foot orthoses relieved patients' knee pain and reduced the descending motor inhibition. Changes in spinal modulation could contribute to a better quality of life. However, this treatment failed to change the altered gait, despite changes in spinal and supraspinal modulation.

Biocompatibility of Four Common Orthopedic Biomaterials Following a High-Salt Diet: An In Vivo Study.

Nowadays, salt consumption appears to be drastically above the recommended level in industrialized countries. The health consequences of this overconsumption are heavy since high-salt intake induces cardiovascular disease, kidney dysfunction, and stroke. Moreover, harmful interaction may also occur with orthopaedic devices because overconsumption of salt reinforces the corrosive aspect of biological tissues and favors bone resorption process. In the present study, we aimed to assess the in vivo effect of three weeks of a high-salt diet, associated (or not) with two weeks of the neuro-myoelectrostimulation (NMES) rehabilitation program on the biocompatibility of four biomaterials used in the manufacture of arthroplasty implants. Thus, two non-metallic (PEEK and Al2O3) and two metallic (Ti6Al4V and CrCo) compounds were implanted in the rat tibial crest, and the implant-to-bone adhesion and cell viability of two surrounded muscles, the Flexor Digitorum (FD) and Tibialis Anterior (TA), were assessed at the end of the experiment. Results indicated lower adhesion strength for the PEEK implant compared to other biomaterials. An effect of NMES and a high-salt diet was only identified for Al2O3 and Ti6Al4V implants, respectively. Moreover, compared to a normal diet, a high-salt diet induced a higher number of dead cells on both muscles for all biomaterials, which was further increased for PEEK, Al2O3, and CrCo materials with NMES application. Finally, except for Ti6Al4V, NMES induced a higher number of dead cells in the directly stimulated muscle (FD) compared to the indirectly stimulated one (TA). This in vivo experiment highlights the potential harmful effect of a high-salt diet for people who have undergone arthroplasty, and a rehabilitation program based on NMES.

Thermogelling chitosan lactate hydrogel improves functional recovery after a C2 spinal cord hemisection in rat.

The present study was designed to provide an appropriate micro-environment for regenerating axotomized neurons and proliferating/migrating cells. Because of its intrinsic permissive properties, biocompatibility and biodegradability, we chose to evaluate the therapeutic effectiveness of a chitosan-based biopolymer. The biomaterial toxicity was measured through in vitro test based on fibroblast cell survival on thermogelling chitosan lactate hydrogel substrate and then polymer was implanted into a C2 hemisection of the rat spinal cord. Animals were randomized into three experimental groups (Control, Lesion and Lesion + Hydrogel) and functional tests (ladder walking and forelimb grip strength tests, respiratory assessment by whole-body plethysmography measurements) were used, once a week during 10 weeks, to evaluate post-traumatic recoveries. Then, electrophysiological examinations (reflexivity of the sub-lesional region, ventilatory adjustments to muscle fatigue known to elicit the muscle metaboreflex and phrenic nerve recordings during normoxia and temporary hypoxia) were performed. In vitro results indicated that the chitosan matrix is a non-toxic biomaterial that allowed fibroblast survival. Furthermore, implanted animals showed improvements of their ladder walking scores from the 4th week post-implantation. Finally, electrophysiological recordings indicated that animals receiving the chitosan matrix exhibited recovery of the H-reflex rate sensitive depression, the ventilatory response to repetitive muscle stimulation and an increase of the phrenic nerve activity to asphyxia compared to lesioned and nonimplanted animals. This study indicates that hydrogel based on chitosan constitute a promising therapeutic approach to repair damaged spinal cord or may be used as an adjuvant with other treatments to enhance functional recovery after a central nervous system damage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2004-2019, 2017.

Influence of Aerobic Training and Combinations of Interventions on Cognition and Neuroplasticity after Stroke.

Stroke often aggravated age-related cognitive impairments that strongly affect several aspects of quality of life. However, few studies are, to date, focused on rehabilitation strategies that could improve cognition. Among possible interventions, aerobic training is well known to enhance cardiovascular and motor functions but may also induce beneficial effects on cognitive functions. To assess the effectiveness of aerobic training on cognition, it seems necessary to know whether training promotes the neuroplasticity in brain areas involved in cognitive functions. In the present review, we first explore in both human and animal how aerobic training could improve cognition after stroke by highlighting the neuroplasticity mechanisms. Then, we address the potential effect of combinations between aerobic training with other interventions, including resistance exercises and pharmacological treatments. In addition, we postulate that classic recommendations for aerobic training need to be reconsidered to target both cognition and motor recovery because the current guidelines are only focused on cardiovascular and motor recovery. Finally, methodological limitations of training programs and cognitive function assessment are also developed in this review to clarify their effectiveness in stroke patients.

Assessment of degradation and biocompatibility of electrodeposited chitosan and chitosan-carbon nanotube tubular implants.

Designing three-dimensional tubular materials made of chitosan is still a challenging task. Availability of such forms is highly desired by tissue engineering, especially peripheral nerve tissue engineering. Aiming at this problem, we use an electrodeposition phenomenon in order to obtain chitosan and chitosan-carbon nanotube hydrogel tubular implants. The in vitro biocompatibility of the fabricated structures is assessed using a mouse hippocampal cell line (mHippoE-18). As both implants do not induce significant cytotoxicity, they are next subjected to in vitro degradation studies in the environment simulating in vivo conditions for specified periods of time: 7, 14, and 28 days. The mass loss of implants indicates their stability at the tested time period; therefore, the materials are subcutaneously implanted in Sprague Dawley rats. The explants are collected after 7, 14, and 28 days. The assessment of composition and changes in tissues surrounding the implanted materials is made in respect to surrounding tissue thickness as well as the number of blood vessels, macrophages, lymphocytes, and neutrophils. No symptoms of acute inflammation are noticed at any point in time. The observed regular healing process allows concluding that both chitosan and chitosan-carbon hydrogel tubular implants are biocompatible with high application potential in tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2701-2711, 2016.

Restoration of post-activation depression of the H-reflex by treadmill exercise in aged rats.

The purpose of this study was to evaluate the effects of aging and chronic physical activity on the postactivation depression of the Hoffman reflex (H-reflex). The maximal amplitude H wave/maximal amplitude M wave ratio was measured, and the rate-sensitive depression of the H-reflex was assessed. Measurements were performed on sedentary rats aged of 3, 6, 12, and 20 months and on animals aged of 12 and 20 months performing an incremental treadmill exercise protocol during the last eight weeks preceding the recordings. At the end of the experiment, the muscle mass and/or body mass ratio was calculated. Results indicated that the H-reflex depression of the tibialis anterior and soleus muscles were present until age of 6 and 12 months, respectively. For the tibialis anterior muscle, results also pointed out a decrease in the relative muscle mass with age and that the exercise allowed to restore the rate-sensitive depression of the H-reflex and to increase the relative muscle mass in comparison with sedentary animals. These findings clearly demonstrate that neural alteration of the spinal cord is prevented by activity in aged rats.

Titanium Implant Impairment and Surrounding Muscle Cell Death Following High-Salt Diet: An In Vivo Study.

AIM OF THE STUDY: High-salt consumption has been widely described as a risk factor for cardiovascular, renal and bone functions. In the present study, the extent to which high-salt diet could influence Ti6Al4V implant surface characteristic, its adhesion to rat tibial crest, and could modify muscle cell viability of two surrounding muscles, was investigated in vivo. These parameters have also been assessed following a NMES (neuro-myoelectrostimulation) program similar to that currently used in human care following arthroplasty. RESULTS: After a three-week diet, a harmful effect on titanium implant surface and muscle cell viability was noted. This is probably due to salt corrosive effect on metal and then release of toxic substance around biologic tissue. Moreover, if the use of NMES with high-salt diet induced muscles damages, the latter were higher when implant was added. Unexpectedly, higher implant-to-bone adhesion was found for implanted animals receiving salt supplementation. CONCLUSION: Our in vivo study highlights the potential dangerous effect of high-salt diet in arthroplasty based on titanium prosthesis. This effect appears to be more important when high-salt diet is combined with NMES.

Functional and Neuromuscular Changes after Anterior Cruciate Ligament Rupture in Rats.

PURPOSE: This study was designed to highlight the functional impairments and the neuromuscular adaptations following an anterior cruciate ligament (ACL) injury in rat. METHODS: Animals were randomized into five groups: control (n = 8), SHAM-1wk (n = 6), SHAM-5wk (n = 8), ACL-1wk (n = 8), and ACL-5wk (n = 8). Rats performed three behavioral tests (the ladder-climbing test, the dynamic weight-bearing distribution, and the dynamic function assessment during locomotion) before the surgery (PRE) and at day (D) 1 (D1), D2, D3, D5, D7, D14, D21, D28, and D35 after ACL transection. Electrophysiological recordings, including responses of muscle metabosensitive afferents to a combination of specific chemical activators, namely, lactic acid and potassium chloride, and the quadriceps motor reflex activity, were performed at D7 (ACL-1wk) and at D35 (SHAM and ACL-5wk). RESULTS: Behavioral results indicated an alteration of both weight-bearing distribution over the four paws and fine motor skills (ladder-climbing test) for the injured animals. Maximal motor reflex amplitude was higher after ACL injury compared with the other groups. Moreover, the regulation of motor reflex induced by metabosensitive afferents was perturbed from the first week after ACL transection, without affecting the response of these muscle afferents to their specific stimuli. CONCLUSIONS: This study brings some new evidence about the motor dysfunctions and spinal adaptations after ACL rupture in rats. Such information might be needed for assessing, in our animal model, the effectiveness of the diverse functional rehabilitation strategies used in human clinic after knee injuries.