Jérôme Laurin

Repair of the injured spinal cord by implantation of a synthetic degradable block copolymer in rat

The present study is designed to assess the properties of a new degradable PLA-b-PHEMA block copolymer hydrogel and its therapeutic effectiveness after implantation following a thoracic spinal cord hemisection on rats. Degradable characteristics and porous aspect of the scaffold are respectively analyzed by the evaluation of its mass loss and by electron microscopy. The biomaterial toxicity is measured through in vitro tests based on motoneuron survival and neurite growth on copolymer substrate. Functional measurements are assessed by the Basso, Beattie and Bresnahan (BBB) and the Dynamic Weight Bearing (DWB) tests during 8 weeks post-surgery. Histological analyses are achieved to evaluate the presence of blood vessels and axons, the density of the glial scar, the inflammatory reaction and the myelination at the lesion site and around it. The results indicate that the synthetic PLA-b-PHEMA block copolymer is a non-toxic and degradable biomaterial that provides support for regenerating axons and seems to limit scar tissue formation. Additionally, the implantation of the porous PLA-b-PHEMA scaffold enhances locomotor improvement. The observed functional recovery highlights the potential benefits of plain tissue engineering material, which can further be optimized by bioactive molecule functionalization or transplanted cell encapsulation.

Physical Exercise as a Diagnostic, Rehabilitation, and Preventive Tool: Influence on Neuroplasticity and Motor Recovery after Stroke.

Stroke remains a leading cause of adult motor disabilities in the world and accounts for the greatest number of hospitalizations for neurological disease. Stroke treatments/therapies need to promote neuroplasticity to improve motor function. Physical exercise is considered as a major candidate for ultimately promoting neural plasticity and could be used for different purposes in human and animal experiments. First, acute exercise could be used as a diagnostic tool to understand new neural mechanisms underlying stroke physiopathology. Indeed, better knowledge of stroke mechanisms that affect movements is crucial for enhancing treatment/rehabilitation effectiveness. Secondly, it is well established that physical exercise training is advised as an effective rehabilitation tool. Indeed, it reduces inflammatory processes and apoptotic marker expression, promotes brain angiogenesis and expression of some growth factors, and improves the activation of affected muscles during exercise. Nevertheless, exercise training might also aggravate sensorimotor deficits and brain injury depending on the chosen exercise parameters. For the last few years, physical training has been combined with pharmacological treatments to accentuate and/or accelerate beneficial neural and motor effects. Finally, physical exercise might also be considered as a major nonpharmacological preventive strategy that provides neuroprotective effects reducing adverse effects of brain ischemia. Therefore, prestroke regular physical activity may also decrease the motor outcome severity of stroke.

The Use of Poly(N-[2-Hydroxypropyl]-Methacrylamide) Hydrogel to Repair a T10 Spinal Cord Hemisection in Rat: A Behavioural, Electrophysiological and Anatomical Examination

There have been considerable interests in attempting to reverse the deficit because of an SCI (spinal cord injury) by restoring neural pathways through the lesion and by rebuilding the tissue network. In order to provide an appropriate micro-environment for regrowing axotomized neurons and proliferating and migrating cells, we have implanted a small block of pHPMA [poly N-(2-hydroxypropyl)-methacrylamide] hydrogel into the hemisected T10 rat spinal cord. Locomotor activity was evaluated once a week during 14 weeks with the BBB rating scale in an open field. At the 14th week after SCI, the reflexivity of the sub-lesional region was measured. We also monitored the ventilatory frequency during an electrically induced muscle fatigue known to elicit the muscle metaboreflex and increase the respiratory rate. Spinal cords were then collected, fixed and stained with anti-ED-1 and anti-NF-H antibodies and FluoroMyelin. We show in this study that hydrogel-implanted animals exhibit: (i) an improved locomotor BBB score, (ii) an improved breathing adjustment to electrically evoked isometric contractions and (iii) an H-reflex recovery close to control animals. Qualitative histological results put in evidence higher accumulation of ED-1 positive cells (macrophages/monocytes) at the lesion border, a large number of NF-H positive axons penetrating the applied matrix, and myelin preservation both rostrally and caudally to the lesion. Our data confirm that pHPMA hydrogel is a potent biomaterial that can be used for improving neuromuscular adaptive mechanisms and H-reflex responses after SCI.

Group III and IV muscle afferent discharge patterns after repeated lengthening and shortening actions.

The purpose of this study was to test the hypothesis that group III and IV muscle afferent activity would differ after concentric‐ and eccentric‐type fatiguing tasks. Tibialis anterior afferent activities from adult rats were measured in three conditions: before and after a rest period (C), and after concentric (CC) or eccentric (EC) exercise. Specific activators were used to elicit increases in afferent discharge rates, i.e., electrically induced fatigue (EIF), or potassium chloride (KCl) and lactic acid (LA) injections. After the rest period (POST‐condition), the control group displayed a pattern of response to stimuli similar to that obtained in baseline condition (PRE‐condition). However, responses were significantly different in the exercise groups: afferent responses were blunted in the CC group and were almost suppressed in the EC group. These results demonstrate that the type of muscular contraction involved in the fatiguing task can affect group III and IV afferent fiber activity differently and, potentially, can differentially affect the regulation of central motor command. Muscle Nerve, 2009

Group III and IV muscle afferents: Role on central motor drive and clinical implications

The present review is focused on neural mechanisms responsible of group III and IV muscle afferent actions on central motor drive during physical exercise in both healthy and pathological populations. It seems that these mechanisms contribute to improve muscle performance by regulating the peripheral fatigue development and by avoiding excessive muscle impairments. Therefore, a great deal of attention is paid to their influences on motor unit activation during fatiguing exercise both in human and animal models. Recent evidence indicated that these afferents from a given active muscle could contribute to regulate the motor activity of the homonymous as well as surrounding skeletal muscles by acting at both spinal and supraspinal levels. In addition, given that the recovery of the sensory feedback plays a key role in the improvement of motor function following numerous neuromuscular traumas, the role of these afferents in preclinical and clinical situations is also explored in animal and human models. It is supposed that studying the motor and autonomic functions of group III and IV afferents might help healthcare professionals in the future to find appropriate treatments and rehabilitation programs.

Neuromuscular recovery pattern after medial collateral ligament disruption in rats

The medial collateral ligament (MCL) is one of the most injured ligaments during sport activities. The resulting joint damage effects on neuromuscular system remain unclear. Thus this study was designed to assess the changes in neuromuscular properties of vastus medialis muscle after MCL transection. Complete rupture of MCL was performed on rats, and dynamic functional assessment during locomotion was achieved before and once a week from 1-5 wk postlesion. Twitch properties and metabo- and mechanosensitive afferent fiber responses to specific stimuli were measured 1, 3, and 5 wk after MCL transection. Results indicated that maximum knee angle measured during the stance phase of the gait cycle was decreased during 3 wk after MCL injury and then recovered. Minimum knee angle measured during the stance phase was decreased during 2 wk and showed compensatory effects at week 5. A stepwise decrease in maximum relaxation rate-to-amplitude ratio concomitant with a stepwise increase in half-relaxation time were observed following MCL injury. Variations in metabosensitive afferent response to chemical (KCl and lactic acid) injections were decreased at week 1 and recovered progressively from week 3 to week 5 postlesion. Recovery of the mechanosensitive afferent response to vibrations was not totally complete after 5 wk. Our data indicate that alteration of the sensory pathways from the vastus medialis muscle could be considered as a source of neuromuscular deficits following MCL transection. Our results should be helpful in clinical purpose to improve the knowledge of the influence exerted by ligament rupture on the motor system and permit development of rehabilitation protocols and exercises more appropriate for recovery of functional stability.

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.

Recovery pattern of motor reflex after a single bout of neuromuscular electrical stimulation session.

We aimed at determining the recovery pattern of neural properties of soleus muscle after a single bout of neuromuscular electrical stimulation (NMES) session. Thirteen subjects performed an NMES exercise (75 Hz, 40 contractions, 6.25 s per contraction). Maximal voluntary contraction (MVC), H‐reflex at rest and during voluntary contraction fixed at 60% of MVC (respectively, Hmax and Hsup) and volitional (V) wave were measured before and during the recovery period following this exercise [i.e., immediately after, 2 h (H2), 2 days (D2) and 7 days (D7)]. MVC exhibited an immediate and a delayed declines at 2 days (respectively, −29.8±4.6%, P<0.001; −13.0±3.4%, P<0.05). Likewise, V/Msup was decreased immediately and 2 days after NMES session (respectively, −43.3±11.6%, P<0.05; 35.3±6.6%, P<0.05). The delayed decrements in MVC and V‐wave occurred concomitantly with muscle soreness peak (P<0.001). It could be concluded that motor command alterations after an NMES resistance session contributed to the immediate and also to the delayed decreases in MVC without affecting resting and active H‐reflex excitability. These results suggested that spinal circuitry function of larger motoneurons was inhibited by NMES (as indicated by the depressed V‐wave responses) contrary to the smaller one (indicated by the unchanged H‐reflex responses).

Neuromuscular recovery after medial collateral ligament disruption and eccentric rehabilitation program.

PURPOSE Medial collateral ligament (MCL) rupture of the knee joint frequently occurs during sport activities. However, the optimal rehabilitation strategy after such lesion is unknown. The aim of this study was to assess the effects of progressive eccentric rehabilitation program on neuromuscular deficits induced by MCL transection. METHODS Rats were randomized as follows: (i) control group (C, n = 10) without any surgery; (ii) lesion groups in which neuromuscular measurements were made 1 (L1, n = 10) and 3 wk (L3, n = 9) after MCL transection by a 15- to 20-min surgery (this group was designed to determine changes induced by the MCL transection); and (iii) eccentric group (ECC, n = 7) in which rats performed a progressive 2-wk eccentric rehabilitation program beginning 1 wk after MCL transection surgery. Dynamic functional assessments were performed at weeks 1 and 3 after the MCL transection by measuring the maximal and minimal knee angles during the stance phase of the gait cycle. Neuromuscular measurements included 1) modulation of H-reflex in response to a 10-mM KCl injection, 2) analysis of the twitch relaxation properties of the quadriceps muscle, and 3) recording of metabosensitive and mechanosensitive afferents activity in response to chemical injections and to tendon patellar vibrations, respectively. RESULTS Our results indicated that H-reflex modulation induced by metabosensitive afferents was disturbed by MCL transection without any recovery despite rehabilitation program. Responses of both metabosensitive and mechanosensitive muscle afferents, as well as the muscle relaxation properties, were fully recovered after the eccentric rehabilitation program. CONCLUSIONS Our results directly indicated an influence of progressive eccentric program on muscle afferents response after MCL section but apparently not for spinal reflex modulation.

Modulation of the Spinal Excitability by Muscle Metabosensitive Afferent Fibers

The aim of this study was to identify the effect of chemical activation of muscle metabosensitive afferent fibers from groups III and IV on Hoffmann (H‐) reflex modulation in the vastus medialis muscle. The experiment was conducted in rats and was divided into two experiments. The first experiment consisted of recording the metabosensitive afferent activity from femoral nerve in rats in response to KCl intraarterial injections in nontreated adults and adults treated neonatally with capsaicin. Thus, the dose‐response curve was determined. The second experiment consisted of eliciting the H‐ and M‐waves before and after KCl injection in nontreated adult animals and those treated neonatally with capsaicin. Thus, the Hmax/Mmax ratio was measured. Results indicated that, 1) in nontreated animals, afferent fibers peak discharge was found after 10 mM KCl injection; 2) no significant increase in afferent discharge rate was found in capsaicin‐treated animal after KCl injections, confirming that capsaicin is an excitotoxic agent that had destroyed the thin metabosensitive nerve fibers; 3) in nontreated animals, Hmax/Mmax ratio was significantly attenuated after a 10 mM KCl injection activating metabosensitive afferent fibers; and 4) in capsaicin‐treated animals, no significant change in Hmax/Mmax ratio was observed after the KCl injection. These results reinforce the hypothesis that the spinal reflex response was influenced by metabosensitive muscle fibers and provide direct evidence that activation of these fibers could partially explain the reported decrease in H‐reflex when metabolites are released in muscle.