Neurotransmitter and receptor systems in the subthalamic nucleus.

The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown. Few studies have specifically addressed the detection of neurotransmitter systems and their receptors within the structure, and even fewer have investigated their topographical distribution. Here, we have reviewed the scientific literature on neurotransmitters relevant in the STh function of rodents, non-human primates and humans including glutamate, GABA, dopamine, serotonin, noradrenaline with particular focus on their subcellular, cellular and topographical distribution. Inter-species differences were highlighted to provide a framework for further research priorities, particularly in humans.

Two-years of home based functional electrical stimulation recovers epidermis from atrophy and flattening after years of complete Conus-Cauda Syndrome.

To evaluate progression of skin atrophy during 8 years of complete Conus-Cauda Syndrome and its recovery after 2 years of surface Functional Electrical Stimulation a cohort study was organized and implemented.Functional assessments, tissue biopsies, and follow-up were performed at the Wilhelminenspital, Vienna, Austria; skin histology and immunohistochemistry at the University of Padova, Italy on 13 spinal cord injury persons suffering up to 10 years of complete conus/cauda syndrome. Skin biopsies (n. 52) of both legs were analyzed before and after 2 years of home-based Functional Electrical Stimulation delivered by large anatomically shaped surface electrodes placed on the skin of the anterior thigh. Using quantitative histology we analyzed: 1. Epidermis atrophy by thickness and by area; 2. Skin flattening by computing papillae per mm and Interdigitation Index of dermal-epidermal junctions; 3. Presence of Langerhans cells.Linear regression analyses show that epidermal atrophy and flattening worsen with increasing years post- spinal cord injury and that 2 years of skin electrostimulation by large anatomically shaped electrodes reverses skin changes (pre-functional Electrical Stimulation vs post-functional Electrical Stimulation: thickness 39%, P < .0001; area 41%, P < .0001; papillae n/mm 35%, P < 0.0014; Interdigitation index 11%, P < 0.018), producing a significant recovery to almost normal levels of epidermis thickness and of dermal papillae, with minor changes of Langerhans cells, despite 2 additional years of complete Conus-Cauda Syndrome.In complete Conus-Cauda Syndrome patients, the well documented beneficial effects of 2 years of surface h-b Functional Electrical Stimulation on strength, bulk, and muscle fiber size of thigh muscles are extended to skin, suggesting that electrical stimulation by anatomically shaped electrodes fixed to the skin is also clinically relevant to counteract atrophy and flattening of the stimulated skin. Mechanisms, pros and cons are discussed.

New bioresorbable wraps based on oxidized polyvinyl alcohol and leukocyte-fibrin-platelet membrane to support peripheral nerve neurorrhaphy: preclinical comparison versus NeuraWrap.

Nerve wrapping improves neurorrhaphy outcomes in case of peripheral nerve injuries (PNIs). The aim of this preclinical study was to assess the efficacy of two novel biodegradable wraps made of a synthetic 1% oxidized polyvinyl alcohol (OxPVA) and a natural leukocyte-fibrin-platelet membrane (LFPm) versus the commercial product NeuraWrap. After rats sciatic nerve transection and neurorrhaphy, the wraps were implanted and compared for functional outcome, by sciatic function index assessment; structural characteristics, by histological/immunohistochemical analysis; ultrastructural features, by transmission electron microscopy. Moreover, a morphometric study was also performed and collagen distribution was observed by Second Harmonic Generation microscopy. After 12 weeks from implantation, all wraps assured nerve function recovery; no scar tissue/neuromas were visible at dissection. LFPm wraps were completely resorbed, while residues of OxPVA and NeuraWrap were observed. In all groups, biocompatibility was confirmed by the absence of significant inflammatory infiltrate. According to histological/immunohistochemical analysis and morphometric findings, OxPVA and LFPm wraps were both effective in preserving nerve integrity. These results assess that bioengineered OxPVA and LFPm wraps successfully guarantee favorable lesion recovery after PNI/neurorrhaphy and, in future, may be considered an interesting alternative to the commercial NeuraWrap.

In complete SCI patients, long-term functional electrical stimulation of permanent denervated muscles increases epidermis thickness.

Our studies have shown that atrophic Quadriceps muscles from spinal cord injury patients suffering with permanent denervation-induced atrophy and degeneration of muscle fibers, were almost completely rescued to normal size after two years of home-based functional electrical stimulation (h-bFES). Because we used surface electrodes to stimulate the muscle, we wanted to know how the skin was affected by the treatments. Here, we report preliminary data from histological morphometry of Hematoxylin-Eosin-stained paraffin-embedded skin sections harvested from the legs of three SCI patients before and after two years of h-bFES. Despite the heterogeneity of gender and time from SCI, comparing pre vs post h-bFES in these three SCI patients, the data show that: (1) In one subject skin biopsies from both the right and left leg experienced a statistically significant increase in thickness of the epidermis after two years of H-bFES; (2) In the other two subjects, one leg showed a significant increase in epidermis thickness, while in the other leg there was either small positive or negative non-significant changes in epidermis thickness; and (3) more importantly, comparison of grouped data from the three subjects shows that there was a significant 28% increase in the thickness of the epidermis in response to two years of h-bFES rehabilitation. In conclusion, the three educational cases show a long-term positive modulation of epidermis thickness after two years of h-bFES, thus extending to skin the positive results previously demonstrated in skeletal muscle, specifically, a substantial recovery of muscle mass and contractile function after long-term h-bFES.

Hyperbaric air exposure at 2.5 ATA does not affect respiratory mechanics and lung histology in the rat.

BACKGROUND: We previously demonstrated that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances, probably because of increased oxygen tension toxic effects. We presently investigated the possible consequences of a single exposure to 2.5-atmospheres absolute air (hyperbarism) lasting 90 min. METHODS: We used the end-inflation occlusion method on anesthetized rats after about 15 min from previous exposure to hyperbarism. The method allows the measurements of respiratory system elastance and of the ohmic and viscoelastic components of airway resistance, which respectively depend on the Newtonian pressure dissipation due to the ohmic airway resistance to airflow and on the viscoelastic pressure dissipation caused by respiratory system tissue stress relaxation. The expressions of inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) in the lung's tissues were also investigated, together with the histological characteristics of lung tissue. Data were compared with those obtained in control animals and in previously studied animals exposed to hyperoxic hyperbarism. RESULTS: Unlike with hyperoxic hyperbarism, hyperbarism per se did not change significantly the parameters of respiratory mechanics in the control animals (respiratory system elastance and ohmic and viscoelastic resistances were 2.01 ± 0.17 vs. 1.74 ± 0.08 cm H(2)O/ml, and 0.13 ± 0.02 vs. 0.13 ± 0.03 and 0.425 ± 0.04 vs. 0.33 ± 0.03 cm H(2)O/ml s(-1) in control vs. experimental animals, respectively, none significantly different), nor did it induce evident effects on lung histology. An increment of both iNOS and eNOS expressions was documented instead (0.50 ± 0.05 vs. 0.75 ± 0.07 and 1.04 ± 0.1 and 1.4 ± 0.15, respectively). CONCLUSION: Our results indicate that, at variance with hyperoxic hyperbarism, the acute exposure to only hyperbarism does not affect either the elastic or the resistive respiratory system properties, or lung histology.

The effect of acute exposure to hyperbaric oxygen on respiratory system mechanics in the rat.

PURPOSE: This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. METHODS: We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. RESULTS: We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. CONCLUSIONS: Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

RMI study and clinical correlations of ankle retinacula damage and outcomes of ankle sprain.

Recent studies reveal the role of the ankle retinacula in proprioception and functional stability of the ankle, but there is no clear evidence of their role in the outcomes of ankle sprain. 25 patients with outcomes of ankle sprain were evaluated by MRI to analyze possible damage to the ankle retinacula. Patients with damage were subdivided into two groups: group A comprised cases with ankle retinacula damage only, and group B those also with anterior talofibular ligament rupture or bone marrow edema. Both groups were examined by VAS, CRTA and static posturography and underwent three treatments of deep connective tissue massage (Fascial Manipulation technique). All evaluations were repeated after the end of treatment and at 1, 3 and 6 months. At MRI, alteration of at least one of the ankle retinacula was evident in 21 subjects, and a further lesion was also identified in 7 subjects. After treatment, VAS and CRTA evaluations showed a statistically significant decrease in values with respect to those before treatment (p < 0.0001). There were also significant improvements (p < 0.05) in stabilometric platform results. No significant difference was found between groups A and B. The initial benefit was generally maintained at follow-up. The alteration of retinacula at MRI clearly corresponds to the proprioceptive damage revealed by static posturography and clinical examination. Treatment focused on the retinacula may improve clinical outcomes and stabilometric data.

The pectoral fascia: anatomical and histological study.

AIM: Analysis of the pectoral fascia from a macroscopic and histological point of view. RESULTS: The pectoral fascia appears as a thin collagen layer (mean thickness of 297 microm) formed by undulated collagen fibres and many elastic fibres, within which small nerves are highlighted. Numerous septa detach from its internal surface, creating an intimate connection between the fascia and the pectoralis major muscle. DISCUSSION: The pectoral fascia and the pectoralis major muscle should be considered together, given that the anatomical base is effectively a myofascial unit, term that defines the muscles and the fascia of a specific region that have a precise functional organization. The capacity of force transmission between the inferior and superior limbs needs to be attributed to this entire myofascial complex. We hypothesize that the superficial, large muscles of the trunk developed inside the superficial layer of the deep fascia to enhance modulation of tension transmission between the different segments of the body.

Anatomical study of myofascial continuity in the anterior region of the upper limb.

Fifteen unembalmed cadavers were dissected in order to study the "anatomical continuity" between the various muscles involved in the movement of flexion of the upper limb. This study demonstrated the existence of specific myofascial expansions, with a nearly constant pattern, which originate from the flexor muscles and extend to the overlying fascia. The clavicular part of the pectoralis major sends a myofascial expansion, with a mean length of 3.6cm, to the anterior region of the brachial fascia, and the costal part sends one to the medial region of the brachial fascia (mean length: 6.8cm). The biceps brachii presents two expansions: the lacertus fibrosus, oriented medially, with a mean height of 4.7cm and a base of 1.9cm, and a second, less evident, longitudinal expansion (mean length: 4.5cm, mean width: 0.7cm). Lastly, the palmaris longus sends an expansion to the fascia overlying the thenar muscles (mean length: 1.6cm, mean width: 0.5cm). During flexion, as these muscles contract, the anterior portion of the brachial and antebrachial fascia is subject to tension. As the fascia is rich in proprioceptive nerve endings, it is hypothesized that this tension activates a specific pattern of receptors, contributing to perception of motor direction. If the muscular fascia is in a non-physiological state, these mechanisms are altered, and the proprioceptors in the fascia may be incorrectly activated, thus giving rise to many types of extra-articular pain.

Histological study of the deep fasciae of the limbs.

The aim of this study is to analyse the deep fasciae of limbs in order to evaluate the collagen and elastic fibre arrangement and the types of innervation. Histological and immunohistochemical stains were performed in 72 specimens. The deep fascia of the limbs is a sheath presenting a mean thickness of 1mm, formed by two to three layers of parallel collagen fibre bundles. In the adjacent layers, they show different orientations. Each layer is separated from the adjacent one by loose connective tissue, permitting the sliding of the collagen layers. Nerve fibres were found in all specimens, while muscular fibres were evidenced only in one specimen. The described structure permits the fasciae of the limbs to have a strong resistance to traction, even when exercised in different directions. The capacity of the different collagen layers to glide one on the other could be altered in cases of overuse syndrome, trauma, or surgery.