Detergent-free Decellularized Nerve Grafts for Long-gap Peripheral Nerve Reconstruction.

Background: Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks.

Peripheral nerve repair through multi-luminal biosynthetic implants.

Peripheral nerve damage is routinely repaired by autogenic nerve grafting, often leading to less than optimal functional recovery at the expense of healthy donor nerves. Alternative repair strategies use tubular scaffolds to guide the regeneration of damaged nerves, but despite the progress made on improved structural materials for the nerve tubes, functional recovery remains incomplete. We developed a biosynthetic nerve implant (BNI) consisting of a hydrogel-based transparent multichannel scaffold with luminar collagen matrix as a 3-D substrate for nerve repair.

Early interfaced neural activity from chronic amputated nerves.

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use.

Carbon nanotube coating improves neuronal recordings.

Implanting electrical devices in the nervous system to treat neural diseases is becoming very common. The success of these brain-machine interfaces depends on the electrodes that come into contact with the neural tissue. Here we show that conventional tungsten and stainless steel wire electrodes can be coated with carbon nanotubes using electrochemical techniques under ambient conditions.

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease.

Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway.

Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease.

The mechanisms that trigger or contribute to loss of dopaminergic (DA) neurons in Parkinson's disease (PD) remain unclear and controversial. Elevated levels of tumor necrosis factor (TNF) in CSF and postmortem brains of PD patients and animal models of PD implicate this proinflammatory cytokine in the pathophysiology of the disease; but a role for TNF in mediating loss of DA neurons in PD has not been clearly demonstrated. Here, we report that neutralization of soluble TNF (solTNF) in vivo with the engineered dominant-negative TNF compound XENP345 (a PEGylated version of the TNF variant A145R/I97T) reduced by 50% the retrograde nigral degeneration induced by a striatal injection of the oxidative neurotoxin 6-hydroxydopamine (6-OHDA).

Activation of type-identified motor units during centrally evoked contractions in the cat medial gastrocnemius muscle. III. Muscle-unit force modulation.

1. The aim of this study was to examine the extent of muscle-unit force modulation due to motoneuron firing-rate variation in type-identified motor units of the cat medial gastrocnemius (MG) muscle, and to investigate the contribution of muscle-unit force modulation to whole-muscle force regulation. The motoneuron discharge patterns recorded from 8 pairs of motor units during 12 smoothly graded muscle contractions evoked by stimulation of the mesencephalic locomotor region (MLR) were used to reactivate those units in isolation to estimate what their force profiles would have been like during the evoked whole-muscle contractions.

Activation of type-identified motor units during centrally evoked contractions in the cat medial gastrocnemius muscle. II. Motoneuron firing-rate modulation.

1. The aim of this study was to examine the nature of motoneuron firing-rate modulation in type-identified motor units during smoothly graded contractions of the cat medial gastrocnemius (MG) muscle evoked by stimulation of the mesencephalic locomotor region (MLR). Motoneuron discharge patterns, firing rates, and the extent of firing-rate modulation in individual units were studied, as was the extent of concomitant changes in firing rates within pairs of simultaneously active units.

Activation of type-identified motor units during centrally evoked contractions in the cat medial gastrocnemius muscle. I. Motor-unit recruitment.

1. The recruitment order of 64 pairs of motor units, comprising 21 type-identified units, was studied during centrally evoked muscle contractions of the cat medial gastrocnemius (MG) muscle in an unanesthetized, high decerebrate preparation. Motor units were functionally isolated within the MG nerve by intra-axonal (or intramyelin) penetration with conventional glass microelectrodes.

Task-dependent nature of fatigue in single motor units.

The loss of force production during sustained activity presents the CNS a unique control problem. Different tasks stress the neuromuscular system at different sites and times, and involve different cellular mechanisms. The functional organization of muscles and their motor units has evolved to avoid fatigue processes that impair motor performance.

Nonuniform fatigue characteristics of slow-twitch motor units activated at a fixed percentage of their maximum tetanic tension.

1. The endurance of slow-twitch motor units from the soleus (SOL) and medial gastrocnemius (MG) muscles of the cat were tested by determining the length of time (endurance time, Et) that a unit could maintain its tension output at 85% of maximum. Motor-unit tension was clamped at the target level by altering the stimulation rate of a unit's motor axon through computer feedback control.

Control of motor-unit tension by rate modulation during sustained contractions in reinnervated cat muscle.

1. The aim of this study was to describe the control of tension by rate modulation of single motor units in reinnervated muscle. 2.

Acute effects of spinal transection on EPSPs produced by single homonymous Ia-fibers in soleus alpha-motoneurons in the cat.

1. Excitatory postsynaptic potentials (EPSPs) generated in soleus motoneurons by single homonymous Ia-fibers were measured using intracellular recording and the spike-triggered averaging technique. Two groups of barbiturate-anesthetized adult cats were studied: one with the spinal cord intact and the other with the spinal cord severed at thoracic segment 13 (T13) several hours prior to recording.

Maximum tension predicts relative endurance of fast-twitch motor units in the cat.

1. The relationships between maximum tetanic tension (P0), endurance time, and axonal conduction velocity (CV) were investigated in fast-twitch motor units of the cat flexor carpi radialis (FCR) and medial gastrocnemius (MG) muscles, and in one flexor digitorum longus (FDL) muscle. Endurance time was the length of time that a unit could maintain 25% of its maximum tetanic tension during a sustained contraction.

Motor-unit stimulation patterns during fatiguing contractions of constant tension.

1. Through computer feedback control, muscle-unit tension was maintained by altering the stimulation rate of a functionally isolated motor axon. The required stimulation patterns and fatigue properties of motor units from the flexor carpi radialis (FCR), flexor digitorum longus (FDL), and medial gastrocnemius (MG) muscles of the cat were studied when tension was maintained or "clamped" at a constant average level (25% of maximum tetanic tension).

Gradation of isometric tension by different activation rates in motor units of cat flexor carpi radialis muscle.

Single motor units of the flexor carpi radialis (FCR) muscle were activated with a series of constant-rate stimulus trains to study the relation between the frequency of activation and isometric tension development (F-T relation). The tension produced by each stimulus train was expressed as a percentage of the maximum tension-time area (Amax) found for a given unit. Between 25 and 75% Amax a clear separation was seen in the rates needed to produce the same relative tension for the F-T curves of slow-twitch (type S) and fast-twitch (type F) units.

Discharge properties of motoneurons supplying distal forelimb muscles in the cat.

Discharge properties of cat cervical motoneurons innervating distal forelimb muscles were investigated by intracellular current injection. Values for rheobase current, afterhyperpolarization duration and several measures of repetitive discharge characteristics were in most respects similar to those obtained for hindlimb motoneurons.

Classification of motor units in flexor carpi radialis muscle of the cat.

Motor units in the cat flexor carpi radialis (FCR) muscle, one of two primary wrist flexors, were classified into three groups: slow twitch, fatigue resistant (S); fast twitch, fatigue resistant (FR); and fast twitch, fatigue sensitive (FF). Classification was based on 1) the ratio of the tension-time area produced by a train of stimuli delivered at 40 pps and the maximum tension-time area (A40/Amax), and 2) the cumulative force index (CFI), calculated from a series of trains (40 pps) delivered intermittently for a period of 4 min. The CFI is defined as the ratio between the force accumulated in the last 2 min of stimulation to the first 2 min of stimulation.

Pressor reflex evoked by muscular contraction: contributions by neuraxis levels.

The pressor reflex evoked by muscular contraction (exercise pressor reflex) is one important model of cardiovascular adjustments during static exercise. The central nervous system (CNS) structures mediating this reflex have remained largely obscure. Therefore, we examined the contribution of selected levels of the neuraxis in mediating the pressor reflex evoked by muscular contraction from stimulation of ventral roots.

Peripheral factors influencing expression of pressor reflex evoked by muscular contraction.

The effect of evoked muscle tension, active muscle mass, and fiber-type composition on the pressor reflex evoked by muscular contraction was examined in decerebrate and anesthetized cats. Muscular contraction was induced by stimulating the L7 and S1 ventral roots with 0.1-ms duration pulses three times motor threshold at various frequencies.

Activation of caudal brainstem cell groups during the exercise pressor reflex in the cat as elucidated by 2-[14C]deoxyglucose.

Cell groups of the caudal brainstem were labeled with 2-[14C]deoxyglucose during the pressor response evoked by contraction of hindlimb muscles (exercise pressor reflex). The nuclear groups which were labeled in excess of control levels included: the lateral reticular nucleus, the inferior olive (medial accessory olive), and the lateral tegmental field (adjacent to the lateral reticular nucleus).

The exercise pressor reflex: evidence for an afferent pressor pathway outside the dorsolateral sulcus region.

Pressor reflexes evoked by muscle contraction following stimulation of the cut distal portions of the L7 and S1 ventral roots were studied in decerebrate unanesthetized cats. Reflex responses evoked by this simulated exercise persisted after lesions were made in the dorsolateral sulcus region of the T13-L1 spinal cord, indicating that this area is not essential for mediation of these reflexes. Additional evidence suggested that the pathway responsible for the exercise pressor reflex located in the surviving spinal cord is most likely bilateral.

Localization of monosynaptic Ia excitatory post-synaptic potentials in the motor nucleus of the cat biceps femoris muscle.

Evidence is presented for the existence of a localization of monosynaptic Ia excitatory post-synaptic potentials (e.p.s.

Distribution of monosynaptic Ia excitatory post-synaptic potentials in the motor nucleus of the cat semitendinosus muscle.

Evidence is presented for a lack of localization of monosynaptic Ia excitatory post-synaptic potentials (e.p.s.

Discharge from total populations of Ia and II afferent fibers in the cat's deefferented medial gastrocnemius muscle during static stretch.

Estimates were made of the changing volumes of discharge arising from the total populations of Ia and II spindle afferent fibers in the cat's deefferented medial gastrocnemius as the muscle was extended stepwise over its excursion range. The estimates were based on values reported elsewhere for (i) the incidence of active units and (ii) their rates of discharge at static muscle lengths normalized against the excursion range of the particular muscle, together with (iii) the numbers of Ia and II afferent fibers in the medial gastrocnemius as derived from a critical review of published information. Curves representing the total discharge of the two afferent types are similar and show three phases: an initial level of spontaneous activity, a somewhat curvilinear rise associated with early recruitment of units during stretch, and rectilinear increase after full recruitment.