Numerous Nerve Research Articles

The Significance of Somatosensory Stimulation to the Hand: Implications for Occupational Therapy Practice

The hands contain numerous nerve endings that are intimately connected to the brain. Mounting evidence supports the concept that willful manipulation of objects contributes to expansion or reorganization of the somatosensory cortex and can produce therapeutic outcomes. In the past decade, research has demonstrated that cortical plasticity can continue throughout adulthood. Brain plasticity is a core principle that demonstrates the ability of the central nervous system to respond to stimuli and modify its structural organization and function as an adaptive response. Occupation-based interventions, which engage the use of the hands, are conceived in this article as a “mindbody” experience because of the vast potential for perceptual learning and neurologic reorganization. Many types of neuroplasticity have been identified, but “activity-dependent neuroplasticity” is an essential concept for occupational therapy practice. In addition, the concept of “cross-modal plasticity” will also be delineated with regard to implications to clinical practice. Guidelines for tactile or somatosensory stimulation will be derived from a systematic review of the neuroscience literature.

Telocytes subtypes in human urinary bladder.

Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and connective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy (TEM) and immunohistochemistry. At this latter aim, we used CD34, PDGFRα, αSMA, c-Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC) characteristics, we identified as TC; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their location. PDGFRα/calret-positive, CD34/c-Kit-negative TC were located in the sub-urothelium and distinct in two subtypes whether, similarly to myofibroblasts, they were αSMA-positive and had attachment plaques. The sub-urothelial TC formed a mixed network with myofibroblasts and were close to numerous nerve endings, many of which nNOS-positive. A third TC subtype, PDGFRα/αSMA/c-Kit-negative, CD34/calret-positive, ultrastructurally typical, was located in the submucosa and detrusor. Briefly, in the human bladder, we found three TC subtypes. Each subtype likely forms a network building a 3-D scaffold able to follow the bladder wall distension and relaxation and avoiding anomalous wall deformation. The TC located in the sub-urothelium, a region considered a sort of sensory system for the micturition reflex, as forming a network with myofibroblasts, possessing specialized junctions with extracellular matrix and being close to nerve endings, might have a role in bladder reflexes. In conclusions, the urinary bladder contains peculiar TC able to adapt their morphology to the organ activity.

Innervation of sinoatrial nodal cardiomyocytes in mouse. A combined approach using immunofluorescent and electron microscopy

Fluorescent immunohistochemistry on the cardiac conduction system in whole mount mouse heart preparations demonstrates a particularly dense and complex network of nerve fibres and cardiomyocytes which are positive to the hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4-positive cardiomyocytes) in the sinoatrial node region and adjacent areas around the root of right cranial vein. The present study was designed to investigate the morphologic and histochemical pattern of nerve fibres and HCN4-positive cardiomyocytes using fluorescent techniques and/or electron microscopy. Adrenergic and cholinergic nerve fibres together with HCN4-positive cardiomyocytes were identified using primary antibodies for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), and the HCN4 channel respectively. Amid HCN4-positive cardiomyocytes, fluorescence and electron microscopy data demonstrated a dense distribution of nerve fibres immunoreactive for ChAT and TH. In addition, novel electron microscopy data revealed that the mouse sinoatrial node contained exclusively unmyelinated nerve fibres, in which the majority of axons possess varicosities with clear mediatory vesicles that can be classified as cholinergic. Synapses occurred without any clear terminal connection with the effector cell, i.e. these synapes were of "en passant" type. In general, the morphologic pattern of innervation of mouse HCN4-positive cardiomyocytes identified using electron microscopy corresponds well to the dense network of nerve fibres demonstrated by fluorescent immunohistochemistry in mouse sinoatrial node and adjacent areas. The complex and extraordinarily dense innervation of HCN4-positive cardiomyocytes in mouse sinoatrial node underpins the importance of neural regulation for the cardiac conduction system. Based on the present observations, it is concluded that the occurrence of numerous nerve fibres nearby atrial cardiomyocytes serves as a novel reliable extracellular criterion for discrimination of SA nodal cardiomyocytes using electron microscopy.

Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus.

Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a role in esophageal function. However, the distribution of TRPV1 nerve fibers in the esophagus is currently not well understood. In the present study, we investigated the distribution of TRPV1 and neurotransmitters released from TRPV1 nerve fibers in the mouse lower esophagus. Furthermore, we investigated changes in the presence of TRPV1 in the mouse model of esophagitis. Numerous TRPV1-immunoreactive nerve fibers were seen in both the submucosal layer and myenteric plexus of the lower esophagus and colocalized with calcitonin gene-related peptide (CGRP). TRPV1 colocalized with substance P in axons in the submucosal layer and myenteric plexus. TRPV1 colocalized with neuronal nitric oxide synthase in the myenteric plexus. We observed some colocalization of CGRP with the vesicular acetylcholine (ACh) transporter, packaging of ACh into synaptic vesicles after its synthesis in terminal cytoplasm, in the submucosal layer and myenteric plexus. In the esophagitis model, the number of the TRPV1 nerve fibers did not change, but their immunoreactive intensity increased compared with sham-operated mice. Inhibitory effect of exogenous capsaicin on electrically stimulated twitch contraction significantly increased in esophagitis model compared with the effect in sham-operated mice. Overall, these results suggest that TRPV1 nerve fibers projecting to both the submucosal and muscle layer of the esophagus are extrinsic spinal and vagal afferent neurons. Furthermore, TRPV1 nerve fibers contain CGRP, substance P, nitric oxide, and ACh. Therefore, acid influx-mediated TRPV1 activation may play a role in regulating esophageal relaxation.

Gene profiling in the dynamic regulation of the lifespan of the myelin sheath structure in the optic nerve of rats.

Aging of the nervous system leads to impairments in cognition and motor skills, and is a major risk factor for several neurological disorders. Recently, numerous nerve function deficits that appear with aging have been found to be a consequence of myelin abnormalities; however, the genetic mechanism of the age‑related alterations in the myelin sheath has not yet been fully elucidated. In the present study, the morphology of the myelin sheath in the optic nerve of rats was analyzed at 10 time‑points throughout life. Marked alterations in the myelin sheath were observed in aging and aged optic nerves, and these became progressively more severe with time. To determine the biological processes affected by aging in the myelin sheath, the age‑related profiling of the myelin sheath in rat optic nerves was established using microarray hybridization at 10 time‑points throughout life, between birth and senescence. From the results, 3,826transcripts associated with the age‑related alterations in the myelin sheath of the optic nerve were identified. It was found that the biological processes most significantly altered by aging were lipid metabolism, the immune response and transmitter transport. This suggests that the downregulation of lipid synthesis genes and the upregulation of immune and neurotransmitter transport genes in aging may be the genetic basis for the age‑related alterations observed in the myelin sheath.

Distribution of TRPVs, P2X3, and parvalbumin in the human nodose ganglion.

Immunohistochemistry for several neurochemical substances, the transient receptor potential cation channel subfamily V member 1 (TRPV1) and 2 (TRPV2), P2X3 receptor, and parvalbumin (PV), was performed on the nodose ganglion, pharynx, and epiglottis in human cadavers. The nodose ganglion was situated beneath the jugular foramen, and had a spindle shape with the long rostrocaudal axis. The pharyngeal branch (PB) issued from a rostral quarter of the nodose ganglion, whereas the superior laryngeal nerve (SLN) usually originated from a caudal half of the ganglion. In the nodose ganglion, sensory neurons were mostly immunoreactive for TRPV1 (89 %) or P2X3 (93.9 %). About 30 % of nodose neurons contained TRPV2 (35.7 %)-or PV (29.9 %)-immunoreactivity (-IR). These neurons mainly had small to medium-sized cell bodies, and were distributed throughout the ganglion. Neurodegenerative profiles such as shrinkage or pyknosis could not be detected in the examined ganglion. Occasionally, TRPV2-IR nerve fibers surrounded blood vessels in the epiglottis as well as in the nasal and oral parts of the pharynx. Isolated TRPV2-IR nerve fibers were also located beneath the epithelium. TRPV1-, P2X3-, or PV-IR nerve endings could not be detected in the pharynx or epiglottis. In the PB and SLN, however, numerous nerve fibers contained TRPV1-, TRPV2-, P2X3-, and PV-IR. The present study suggests that TRPV1-, TRPV2-, P2X3-, and PV-IR neurons in the human nodose ganglion innervate the pharynx and epiglottis through the PB and SLN. These neurons may respond to chemical, thermal, and mechanical stimuli during respiration and swallowing.

Innervation of cardiac ventricles: an immunohistochemical study in bats (LB46)

Neuroanatomy of cardiac ventricles in bats that are adapted for 5‐7 month long hibernation was not identified so far. We used fluorescent immunolabeling for PGP9.5, TH, ChAT, nNOS, SP, and CGRP in order to detect general, sympathetic, vagal and sensory neural structures on ventricles of three species of hibernating bats. We found ventricles in bats to be highly innervated by a dense ganglionated nerve plexus scattered up to heart apex. Ventricular neurons were mostly positive (+) for ChAT, fewer – for TH or nNOS. Small intensely fluorescent cells, strongly TH(+), were identified as well. Epicardial nerves possessed the CGRP(+) and SP(+) nerve fibers. Employing immunohistochemistry for PGP9.5, we revealed numerous sensory nerve endings distributed widely beneath the mesothelium. These nerve endings were solely positive for PGP 9.5 and possessed a complex morphology that was not demonstrated previously. The present findings offer insights into further studies of the hibernating myocardial cells that are fully resistant to long term hypoxia and apparently controlled by autonomic nervous system in perfection.Grant Funding Source: Supported by the Research Council of Lithuania (MIP‐031/2013)

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517-2788; aged) vs. 2118 ± 108 (range 1513-2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well-developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans.

Pacinian neuromas presenting as soft tumors on the volar aspect of the fingertips.

Dear Editor: Pacinian neuroma is a rare benign skin tumor characterized by the proliferation of normal-sized or enlarged Pacinian corpuscles1, presenting as a tender, flesh-colored, single papule or nodule that usually occurs on the volar aspect of the fingertip. To the best our knowledge, multiple soft tumor-like Pacinian neuromas have never been reported in the English-language literature. We report a case of flesh-colored soft masses in the digits of a 55-year-old Korean man. The masses had been slowly growing during a 4-year period. He was a butcher by profession, and therefore, he had used a knife to dress meat for a long time. Considering his medical history, he had experienced right-sided hemiplegia after a cerebral hemorrhage 2 years ago. Therefore, he felt no sensation from the skin lesions. Physical examination revealed ill-demarcated, 1.5 cm, flesh-colored, protruding soft masses on the volar aspect of the right fourth and fifth fingertips (Fig. 1A). Skin biopsies were performed, and the pathologic findings were consistent with Pacinian neuromas having increased dermal fibrosis and adnexal structures (Fig. 1B). Fig. 1 (A) Flesh-colored, protruding, 1.5-cm soft tumor-like masses on the volar aspect of the right fourth and fifth fingertips. (B) Multiple (left) or enlarged (top right) Pacinian corpuscles in the subcutaneous tissue surrounded by numerous nerve fibers. ... The patient did not want any treatment; therefore, he had only been observed closely. Pacinian corpuscles are the largest sensory nerve-end organs located in the deep dermis and subcutis, and they function as tactile receptors2. Pacinian neuroma occurs mainly in middle-aged adults and can occur in any finger. According to previous reports, Pacinian neuroma clinically appears as a tiny papule or nodule, and it is usually accompanied by local tenderness. Sometimes, patients have no visible skin lesions3,4. The etiology of Pacinian neuroma is unclear; however, some reports have proposed that repetitive trauma may be among the important precipitating factors5. Our patient had a clear history of repetitive trauma; therefore, this case strongly supports that hypothesis. Rhode and Jennings3 described 4 types of Pacinian neuroma histologically, which are as follows: (1) a single enlarged Pacinian corpuscle, (2) a grape-like structure of normalsized Pacinian corpuscles, (3) slightly enlarged Pacinian corpuscles arranged in tandem, and (4) hyperplastic Pacinian corpuscles arranged along the entire length of the digital nerve. Later, Reznik et al.1 considered types C and D as the same category. Important considerations within the differential diagnoses include neural-origin tumors such as schwannoma and glomus tumor. However, sometimes, other benign skin tumors such as mucoid cysts and fibromas could be considered as a differential diagnosis. The treatment of choice is surgical excision including the deep dermis and subcutis. In this case, the Pacinian neuromas appeared as exceptionally large, protruding masses, and we believe that they may have been induced by the accompanying dermal fibrosis and proliferation of the adnexal tissues. A literature review produced no reports of multiple and soft tumor-like Pacinian neuromas. Therefore, we herein report a case of uniquely presenting multiple Pacinian neuromas.

Expression and distribution of GABA and GABAB-receptor in the rat adrenal gland.

The inhibitory effects of gamma-aminobutyric acid (GABA) in the central and peripheral nervous systems and the endocrine system are mediated by two different GABA receptors: GABAA-receptor (GABAA-R) and GABAB-receptor (GABAB-R). GABAA-R, but not GABAB-R, has been observed in the rat adrenal gland, where GABA is known to be released. This study sought to determine whether both GABA and GABAB-R are present in the endocrine and neuronal elements of the rat adrenal gland, and to investigate whether GABAB-R may play a role in mediating the effects of GABA in secretory activity of these cells. GABA-immunoreactive nerve fibers were observed in the superficial cortex. Some GABA-immunoreactive nerve fibers were found to be associated with blood vessels. Double-immunostaining revealed GABA-immunoreactive nerve fibers in the cortex were choline acetyltransferase (ChAT)-immunonegative. Some GABA-immunoreactive nerve fibers ran through the cortex toward the medulla. In the medulla, GABA-immunoreactivity was seen in some large ganglion cells, but not in the chromaffin cells. Double-immunostaining also showed GABA-immunoreactive ganglion cells were nitric oxide synthase (NOS)-immunopositive. However, neither immunohistochemistry combined with fluorescent microscopy nor double-immunostaining revealed GABA-immunoreactivity in the noradrenaline cells with blue-white fluorescence or in the adrenaline cells with phenylethanolamine N-methyltransferase (PNMT)-immunoreactivity. Furthermore, GABA-immunoreactive nerve fibers were observed in close contact with ganglion cells, but not chromaffin cells. Double-immunostaining also showed that the GABA-immunoreactive nerve fibers were in close contact with NOS- or neuropeptide tyrosine (NPY)-immunoreactive ganglion cells. A few of the GABA-immunoreactive nerve fibers were ChAT-immunopositive, while most of the GABA-immunoreactive nerve fibers were ChAT-immunonegative. Numerous ChAT-immunoreactive nerve fibers were observed in close contact with the ganglion cells and chromaffin cells in the medulla. The GABAB-R-immunoreactivity was found only in ganglion cells in the medulla and not at all in the cortex. Immunohistochemistry combined with fluorescent microscopy and double-immunostaining showed no GABAB-R-immunoreactivity in noradrenaline cells with blue-white fluorescence or in adrenaline cells with PNMT-immunoreactivity. These immunoreactive ganglion cells were NOS- or NPY-immunopositive on double-immunostaining. These findings suggest that GABA from the intra-adrenal nerve fibers may have an inhibitory effect on the secretory activity of ganglion cells and cortical cells, and on the motility of blood vessels in the rat adrenal gland, mediated by GABA-Rs.

Lymphatic and nerve distribution throughout the parametrium

BackgroundOur objective was to concomitantly assess distribution of lymphatic and nerve structures in the parametrium. MethodsTwenty hemipelvises from ten fresh cadavers were dissected to differentiate between, three different parts of the parametrium: the lateral parametrium, the proximal and the distal part of the posterior parametrium. Histologic and immunofluorescence analyses of nerve and lymphatic structures were performed using NSE and LYVE-1 staining, respectively. The percentage of structures was independently scored as 0 (0%), 1 (1–20%), 2 (20–50%), 3 (50–80%), 4 (>80%). ResultsThe lateral parametrium and the proximal part of the posterior parametrium contained both nerve (scored 2.25 and 2.50, respectively) and lymphatic (scored 2.50 and 2.00, respectively) structures. The distal part of the posterior parametrium also contained numerous nerve structures (scored 2.00) but lymphatic structures were rare (scored 0.88). No difference in nerve distribution was found according to the parts of parametrium while a significantly lower distribution of lymphatic vessels was observed in the distal part of the posterior parametrium (p=0.03). ConclusionThe distal part of the posterior parametrium is of high nerve density and low lymphatic density raising the issue as to whether it should be removed during radical hysterectomy.

The new wave of Carpal Tunnel Syndrome (CTS) Surgery

Carpal tunnel syndrome (CTS) is the most common hand disease. The clinical prevalence in the general popula- 1 tion is 3.8%. From a study of Australian population, peo- ple younger than 25 had a 2.4% prevalence compared to an ex- tremely high prevalence in 45 to 65 year-olds who had a 45.5% prevalence.2 In all carpal tunnel syndrome cases, in patients who developed numbness, and experienced symptoms for more than 6 months or did not receive adequate conservative treatment needed further treatment of surgery (Figure 1). The incidence of surgery is high: up to 31% to 40% of patients with carpal tunnel syndrome.3,4 If the patients had severe compression and develop thenar muscle atrophy, the treatment has to be performed and ur- gent decompression is necessary to enable potential full recovery.5 Because carpal tunnel syndrome is the most common hand disease with the highest functional recovery of treatments, patients need to know and look for an update on treatment information. Nowa- days, surgical treatment had been in continuous development in terms of minimal invasive surgery. There has been a great para- digm shift from standard large open surgery to minimal invasive surgery based on patients benet and recovery. Also CTS is one of the benecial changes with the concept of minimal incision because of minimal dissection of highly sensitive numerous nerve areas, minimal trauma, rapid recovery and less complications.

Alarista succina gen. et sp. nov. (Poaceae: Bambusoideae) in Dominican amber

Alarista succina gen. et sp. nov. (Poaceae) is described from a single floret preserved in amber of Tertiary age originating from the Dominican Republic. The new genus is characterised by (1) a narrow-winged lemma awn, (2) numerous (as many as 17) lemma nerves, (3) a lengthy rachilla internode (implying a lax spikelet), (4) sinuous-margined long cells, (5) silica cells arranged transversely, (6) stomatal subsidiaries low domed and (7) papillae. The epidermal features are characteristic of the abaxial leaf blade surface of members of the Bambusoideae and the fossil is placed in this group. htp://zoobank.org/033FCBF4-CD61-4C85-97E4-8418C9ABA5E6

Co-expression pattern of dopamine beta-hydroxylase (DβH) and neuropeptide Y (NPY) within sympathetic innervation of ovary and umbilical cord of the European bison (Bison bonasus L.)

Co-expression of dopamine β-hydroxylase (DβH) and neuropeptide Y (NPY) has never been examined in ovary (OV) and umbilical cord (UC) of the European bison (Eb), the endangered wild species. The OV and UC samples were harvested from seasonally eliminated Eb females (45-120 days post coitum). Frozen histological sections were examined by double fluorescent immunohistochemistry (dF-IHC), using the primary mouse anti-DβH monoclonals and rabbit anti-NPY polyclonals and then the immunocomplexes were visualized with FITC and CY3 fluorophores, respectively. Numerous DβH immunoreactive nerve fibers (DβH-IRs) and a little less frequent NPY-IRs were found in the bundle-like structures, innervating mainly perivascular regions of the OV. The NPY-IRs constantly co-expressed DβH, while some DβH-IRs did not express NPY. This specific pattern of innervation was observed both in the stromal and cortical regions of the OV. The simultaneous co-expression of DβH and NPY were also detected in the UC, in which specific single or bundle-like structures ran along the smooth muscles of blood vessels. The spatial-specific co-expression of DβH and NPY in OV and UC, may suggest that these markers are involved in the control of vascularization that regulates nourishing blood circulation required for proper pregnancy maintenance and efficient embryo/fetus development in the Eb.

Innervation pattern at the undersurface of the extensor carpi radialis brevis tendon in recalcitrant tennis elbow

PurposeWe investigated the general, sensory, and sympathetic innervation patterns at the undersurface of the extensor carpi radialis brevis (ECRB) origin in patients with recalcitrant tennis elbow. MethodsEight elbows in eight consecutive patients (6 females and 2 males) with tennis elbow who underwent arthroscopic surgery were included in this study. The mean age was 45years (38–66years), and the mean duration of symptoms before surgery was 23months (13–52months). Operative treatment consisted of an arthroscopic inspection and debridement of the ECRB origin. Control tissues were obtained from biopsy of the ECRB capsule in two patients with osteochondritis dissecance of the capitellum who underwent arthroscopic resection of loose bodies. The tissue specimens were investigated immunohistochemically with antibodies delineating general (PGP9.5), sensory (SP/CGRP), and sympathetic (NPY) nerve patterns. ResultsIn the non-tendinosis control tissue, SP/CGRP and NPY immunoreactions were heterogeneously distributed in association with blood vessels. Pathologic evaluation of the biopsy tissue showed atypical fibrous granulation containing numerous vessels and nerve structures in all eight patients. Marked reactions to PGP 9.5 took the form of nerve fibers associated with arteries and arterioles in the atypical granulation. Most of the perivascular innervation was found to express NPY. The immunoreactions for SP and CGRP were invariably weak. ConclusionIncreased perivascular sympathetic innervation accompanied with loss of sensory innervation at the undersurface of the ECRB tendon may play a role in chronic pain generation in recalcitrant tennis elbow. Level of evidenceDiagnostic, Level IV.

Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism

Neuropeptide Y is a novel bioactive substance that plays a role in the modulation of neurogenesis and neurotransmitter release, and thereby exerts a protective influence against neurodegeneration. Using a sensitive immunohistochemical method with a tyramide signal amplification protocol, we performed a post-mortem analysis to determine the striatal localization profile of neuropeptide Y in neurologically normal individuals and in patients with X-linked dystonia-parkinsonism, a major representative of the neurodegenerative diseases that primarily involve the striatum. All of the patients examined were genetically verified as having X-linked dystonia-parkinsonism. In normal individuals, we found a scattered distribution of neuropeptide Y-positive neurons and numerous nerve fibres labelled for neuropeptide Y in the striatum. Of particular interest was a differential localization of neuropeptide Y immunoreactivity in the striatal compartments, with a heightened density of neuropeptide Y labelling in the matrix compartment relative to the striosomes. In patients with X-linked dystonia-parkinsonism, we found a significant decrease in the number of neuropeptide Y-positive cells accompanied by a marked loss of their nerve fibres in the caudate nucleus and putamen. The patients with X-linked dystonia-parkinsonism also showed a lack of neuropeptide Y labelling in the subventricular zone, where a marked loss of progenitor cells that express proliferating cell nuclear antigen was found. Our results indicate a neostriatal defect of the neuropeptide Y system in patients with X-linked dystonia-parkinsonism, suggesting its possible implication in the mechanism by which a progressive loss of striatal neurons occurs in X-linked dystonia-parkinsonism.

Gamma‐aminobutyric acid B Receptor Immunoreactivity in the Mouse Adrenal Medulla

The present study examined gamma-aminobutyric acid B (GABAB ) receptor, GABA, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS) immunoreactivities in the mouse adrenal medulla. GABAB receptor immunoreactivity was seen in numerous chromaffin cells and in a few ganglion cells of the adrenal medulla. By using a formaldehyde-induced fluorescence (FIF) method, GABAB receptor immunoreactivity was observed in numerous adrenaline (A) cells, but not in noradrenaline (NA) cells showing blue-white fluorescence. This suggests that GABAB receptors may be present in the A cells and be related to the secretory activity of A cells but not NA cells in the mouse adrenal medulla. GABAB receptor immunoreactive ganglion cells were shown to be nNOS immunopositive by using a double immunostaining method. Weak GABA immunoreactivity was visible in some chromaffin cells and in the numerous nerve fibers of the medulla. By using the FIF method, weak GABA-immunoreactive chromaffin cells were shown to be in the NA cells showing blue-white fluorescence. GABA-immunoreactive nerve fibers were in dense contact in A cells, but not NA cells. GABA-immunoreactive nerve fibers closely contacted a few ganglion cells. Numerous GABA-immunoreactive nerve fibers in the medulla showed ChAT immunoreactive. This result suggests that GABA and acetylcholine may be released from the same nerve fibers and may have a secretory effect on the A cells of the medulla.

The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin.

Innervation of the mammalian pineal gland during prenatal development is poorly recognized. Therefore, immunofluorescence studies of the pineals of 70- and 90-day-old foetuses of the domestic pig were performed using antibodies against tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON). The investigated glands were supplied by numerous nerve fibres containing TH and DβH. The density of these fibres was higher in the distal and middle parts of the gland than in the proximal one. NPY and CPON were identified in the majority of DβH-positive fibres as well as in a small population of DβH-negative fibres localized mainly in the proximal part of the pineal. The immunoreactive fibres were more numerous in 90-day-old foetuses than in 70-day-old ones. The effect of norepinephrine on melatonin secretion by the foetal pineals in the short-term organ culture was studied to determine the role of DβH-positive fibres during prenatal life. For the same purpose melatonin was measured in the blood in the umbilical cords and in the jugular vein of the mother. The pineals of both groups of foetuses did not secrete melatonin in the organ culture, independently of the presence or absence of norepinephrine in the medium. Melatonin concentrations in the blood in the umbilical cords of foetuses from the same litter and in the jugular vein of their mother were similar. The presence of adrenergic nerve fibres in the pig pineal during gestation does not seem to be associated with the control of melatonin secretion.

Catheter-based renal denervation: a word of caution

Hypertension is a major cardiovascular risk factor, and despite the availability of effective antihypertensive drugs the percentage of patients with blood pressure at target values remains low. Especially patients who cannot be controlled by conventional drug treatment are at increased risk of cardiovascular events, which supports the need for greater efforts toward improving hypertension outcomes in this population 1 . Recently, catheter-based renal denervation has been introduced into the market as a new and promising technology to reduce sympathetic activity and blood pressure in patients with resistant hypertension 2 . The first-in man (FIM) study was performed using a radiofrequency-based approach (Symplicity, Ardian/Medtronic, Mountain View, CA, USA) and provided evidence for the concept of renal nerve ablation as an antihypertensive treatment 3 . Numerous new percutaneous renal nerve ablation systems are currently being tested and will soon be released into the market. Already in 2012 five CE-marked renal denervation systems using different treatment strategies are available: Medtronic’s Symplicity, St. Jude’s EnligHTN, Vessix’s V2, Covidien’s OneShot and Recor’s Paradise. Most of these systems use radiofrequency energy to target renal sympathetic nerves except for the Recor’s Paradise system which uses ultrasound 4 . Up to now, the largest – albeit in patient numbers still limited – clinical experience with the longest follow-up has been obtained with the Symplicity catheter system. In this issue of EuroIntervention, Ormiston and colleagues present a first-in-man report of a 75-year-old woman with resistant hypertension who underwent renal denervation using a low-pressure balloon (1 atm) with a mono-polar silver electrode (helical configuration) system (9 Fr), allo wing a straightforward radiofrequency ablation. One and six months after the procedure both office and ambulatory 5 Article, see page 1090 blood pressure significantly decreased, in line with the reductions reported in trials using other devices. As mentioned by the authors, the patient was treated as part of the Maya Renal Hypertension Ablation System trial (NCT01520506), aimed at investigating the safety and effectiveness of renal denervation in 40 patients with resistant hypertension. However, neither this study on a larger cohort of patients nor preclinical studies in porcine models have been published so far. In the light of the huge market for renal denervation systems all over the world a word of caution is required. Despite the request to optimise the interventional profile, reduce the treatment time and thereby radiation exposure, all devices, and especially those using new treatment modalities, have to show favourable safety and efficacy profiles in a larger cohort of patients with subsequent followup before general use can be recommended. Recently, concerns have been raised that renal denervation might induce renal artery stenosis. Two case reports have been published describing a secondary rise in blood pressure after renal denervation caused by a progression of a renal artery stenosis 6,7 . It remains unanswered to

Cephalic sensory influence on forelimb movement in newborn opossums, Monodelphis domestica

Like other marsupials, the opossum Monodelphis domestica is born very immature and crawls, unaided by the mother, from the urogenital opening to a nipple where it attaches and pursues its development. If the alternate, rhythmic movements of the forelimbs which allow this locomotion are generated by the developing spinal motor networks, sensory information is nonetheless needed to guide the newborn to a nipple. Behavioral, anatomical and physiological studies suggest that the auditory and the visual systems are insufficiently developed in newborn opossums to influence spinal motor centers, while the vestibular, trigeminal, and olfactory systems are likelier candidates. The trigeminal, vestibular and olfactory regions of the brain were electrically stimulated to test their relative effectiveness at eliciting forelimb movement in newborn opossums, using in vitro preparations of brain-spinal cord with the limbs attached. The minimal stimulation of the cervical spinal cord needed to induce forelimb movement was considered as threshold (T). Stimulations of the trigeminal ganglion (5G) at ∼2T and of the vestibular complex at ∼20T could induce the same movement, and were not statistically different, in contrast to the ∼600T necessary for the olfactory bulb (OB). Neurofilament-200 immunohistochemistry and retrograde tracing with Texas-Red conjugated Dextran Amines were used to study trigeminal innervation of the facial skin and pathways by which trigeminal inputs may be relayed to the spinal cord. Numerous nerve fibers were observed in the snout dermis, especially in the maxillary region, but also elsewhere in the head skin. Some 5G cells project to the upper spinal cord, but more project to the caudal medulla where they could contact secondary trigeminal neurons or reticular cells projecting to the spinal cord. These results support a significant influence of the trigeminal and the vestibular systems, but not of olfaction, on forelimb movement of neonatal opossums.