SciCombinator

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Concept: Nerve

175

Vestimentiferan tubeworms are marine invertebrates that inhabit chemosynthetic environments, and although recent molecular phylogenetic analyses have suggested that vestimentiferan tubeworms are derived from polychaete annelids, they show some morphological features that are different from other polychaetes. For example, vestimentiferans lack a digestive tract and have less body segments and comparative neuroanatomy can provide essential insight into the vestimentiferan body plan and its evolution. In the present study, we investigated the adult nervous system in the vestimentiferan Lamellibrachia satsuma using antibodies against synapsin, serotonin, FMRMamide and acetylated α-tubulin. We also examined the expressions of neural marker genes, elav and synaptotagmin to reveal the distribution of neuronal cell bodies. Brain anatomy shows simple organization in Lamellibrachia compared to other polychaetes. This simplification is probably due to the loss of the digestive tract, passing through the body between the brain and the subesophageal ganglion. In contrast, the ventral nerve cord shows a repeated organizational structure as in the other polychaetes, despite the absence of the multiple segmentation of the trunk. These results suggest that the brain anatomy is variable depending on the function and the condition of surrounding tissues, and that the formation of the rope ladder-like nervous system of the ventral nerve cord is independent from segmentation in polychaetes.

Concepts: Nervous system, Neuron, Brain, Arthropod, Human brain, Axon, Nerve, Siboglinidae

167

BACKGROUND: Tendon transfers are essential for reconstruction of hand function in tetraplegic patients. To transfer the extensor carpi radialis longus (ECRL), the extensor carpi radialis brevis (ECRB) has to be sufficiently strong. However, there is currently no reliable clinical test to individually analyse both muscles. In order to develop a reliable preoperative clinical test, the anatomy of the muscle (innervation) areas of ECRB, ECRL and brachio-radialis (BR) was examined. METHODS: In 20 arms, the ECRB, ECRL and BR were dissected and localised. Subsequently, muscle-innervation points were mapped and categorised. A novel method, computer-assisted surgical anatomy mapping (CASAM), was used to visualise muscle areas and innervation points in a computed arm with average dimensions. RESULTS: For both ECRL and ECRB a 100% area could be identified, a specific area in the computed average arm in which the muscle was present for all 20 arms. For the ECRL, this area was situated at 16% of the distance between the lateral epicondyle and the deltoid muscle insertion. The ECRB 100% area was 5 times bigger than that of the ECRL and was located at 40% of the distance between the lateral epicondyle and the radial styloid process. The ECRL and BR showed one to three innervation points, the ECRB one to four. In 47% of the cases, there was a combined nerve branch innervating both the ECRL and the ECRB. CONCLUSIONS: It is feasible to develop a preoperative test; the 100% areas can be used for needle electromyography (EMG) or local anaesthetic muscle injections.

Concepts: Muscle, Electromyography, Nerve, Upper limb anatomy, Brachioradialis, Flexor carpi radialis muscle, Extensor carpi radialis brevis muscle, Extensor carpi radialis longus muscle

147

The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS.

Concepts: Inflammation, Central nervous system, Nervous system, Brain, Blood vessel, Smooth muscle, Nerve, Meninges

143

Mephedrone (MEPH) is a β-ketoamphetamine stimulant drug of abuse that is often a constituent of illicit bath salts formulations. While MEPH bears remarkable similarities to methamphetamine (METH) in terms of chemical structure, as well as its neurochemical and behavioral effects, it has been shown to have a reduced neurotoxic profile compared to METH. The addition of a β-keto moiety and a 4-methyl ring substituent to METH yields MEPH, and a loss of direct neurotoxic potential. In the present study, 2 analogs of METH, methcathinone (MeCa) and 4-methylmethamphetamine (4MM), were assessed for their effects on mouse dopamine (DA) nerve endings to determine the relative contribution of each individual moiety to the loss of direct neurotoxicity in MEPH. Both MeCa and 4MM caused significant alterations in core body temperature as well as locomotor activity and stereotypy, but 4MM was found to elicit minimal dopaminergic toxicity only at the highest dose. By contrast, MeCa caused significant reductions in all markers of DA nerve ending damage over a range of doses. These results lead to the conclusion that ring substitution at the 4-position profoundly reduces the neurotoxicity of METH, whereas the β-keto group has much less influence on this property. While the mechanism(s) by which the 4-methyl substituent reduces METH-induced neurotoxicity remains unclear, it is speculated that this effect is mediated by a loss of DA-releasing action in MEPH and 4MM at the synaptic vesicle monoamine transporter, an effect that is thought to be critical for METH-induced neurotoxicity.

Concepts: Nervous system, Attention-deficit hyperactivity disorder, Nerve, Stimulant, Cocaine, Methamphetamine, Narcolepsy, Methcathinone

81

Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede (Scolopendra subspinipes mutilans, ∼3 g) can subdue a mouse (∼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede’s venom. The study indicates that centipedes' venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation.

Concepts: Protein, Neuron, Centipede, Arthropod, Nerve, Scolopendra subspinipes, Centipedes, Scolopendra gigantea

81

The prognosis for recovery of motor function in motor complete spinal cord injured (SCI) individuals is poor. Our research team has demonstrated that lumbosacral spinal cord epidural stimulation (scES) and activity-based training can progressively promote the recovery of volitional leg movements and standing in individuals with chronic clinically complete SCI. However, scES was required to perform these motor tasks. Herein, we show the progressive recovery of voluntary leg movement and standing without scES in an individual with chronic, motor complete SCI throughout 3.7 years of activity-based interventions utilizing scES configurations customized for the different motor tasks that were specifically trained (standing, stepping, volitional leg movement). In particular, this report details the ongoing neural adaptations that allowed a functional progression from no volitional muscle activation to a refined, task-specific activation pattern and movement generation during volitional attempts without scES. Similarly, we observed the re-emergence of muscle activation patterns sufficient for standing with independent knee and hip extension. These findings highlight the recovery potential of the human nervous system after chronic clinically motor complete SCI.

Concepts: Central nervous system, Nervous system, Neuron, Nerve, Paralysis

49

Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting.

Concepts: Muscle, Muscular system, Nerve

39

The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.

Concepts: Central nervous system, Nervous system, Action potential, Neuroscience, Axon, Nerve, Spinal nerve, Somatic nervous system

35

We tested the hypothesis that the nervous system, and the cortex in particular, is a critical determinant of muscle strength/weakness and that a high level of corticospinal inhibition is an important neurophysiologic factor regulating force generation. A group of healthy individuals underwent 4-weeks of wrist-hand immobilization to induce weakness. Another group also underwent 4-weeks of immobilization, but they also performed mental imagery of strong muscle contractions five days/wk. Mental imagery has been shown to activate several cortical areas that are involved with actual motor behaviors- including premotor and M1 regions. A control group, who underwent no interventions, also participated in this study. Before, immediately after, and one-week following immobilization, we measured wrist flexor strength, VA, and the cortical silent period (SP; a measure that reflect corticospinal inhibition quantified via transcranial magnetic stimulation). Immobilization decreased strength 45.1±5.0%, impaired VA 23.2±5.8%, and prolonged the SP 13.5±2.6%. Mental imagery training, however, attenuated the loss of strength and VA by ~ 50% (23.8±5.6% and 12.9±3.2% reductions, respectively), and eliminated prolongation of the SP (4.8±2.8% reduction). Significant associations were observed between the changes in muscle strength and VA (r=0.56) and SP (r=-0.39). These findings suggest neurological mechanisms, most likely at the cortical level, contribute significantly to disuse-induced weakness, and that regular activation of the cortical regions via imagery attenuates weakness and VA by maintaining normal levels of inhibition.

Concepts: Nervous system, Brain, Cerebral cortex, Neurology, Muscle contraction, Muscular system, Transcranial magnetic stimulation, Nerve

34

Exercise-related transient abdominal pain (ETAP), commonly referred to as ‘stitch’, is an ailment well known in many sporting activities. It is especially prevalent in activities that involve repetitive torso movement with the torso in an extended position, such as running and horse riding. Approximately 70 % of runners report experiencing the pain in the past year and in a single running event approximately one in five participants can be expected to suffer the condition. ETAP is a localized pain that is most common in the lateral aspects of the mid abdomen along the costal border, although it may occur in any region of the abdomen. It may also be related to shoulder tip pain, which is the referred site from tissue innervated by the phrenic nerve. ETAP tends to be sharp or stabbing when severe, and cramping, aching, or pulling when less intense. The condition is exacerbated by the postprandial state, with hypertonic beverages being particularly provocative. ETAP is most common in the young but is unrelated to sex or body type. Well trained athletes are not immune from the condition, although they may experience it less frequently. Several theories have been presented to explain the mechanism responsible for the pain, including ischemia of the diaphragm; stress on the supportive visceral ligaments that attach the abdominal organs to the diaphragm; gastrointestinal ischemia or distension; cramping of the abdominal musculature; ischemic pain resulting from compression of the celiac artery by the median arcuate ligament; aggravation of the spinal nerves; and irritation of the parietal peritoneum. Of these theories, irritation of the parietal peritoneum best explains the features of ETAP; however, further investigations are required. Strategies for managing the pain are largely anecdotal, especially given that its etiology remains to be fully elucidated. Commonly purported prevention strategies include avoiding large volumes of food and beverages for at least 2 hours prior to exercise, especially hypertonic compounds; improving posture, especially in the thoracic region; and supporting the abdominal organs by improving core strength or wearing a supportive broad belt. Techniques for gaining relief from the pain during an episode are equivocal. This article presents a contemporary understanding of ETAP, which historically has received little research attention but over the past 15 years has been more carefully studied.

Concepts: Muscle, Liver, Abdominal pain, Stomach, Abdomen, Nerve, Thorax, Human abdomen