Apart from motor and sensory function loss, an injury to the spinal cord can cause sympathetic dysfunction, which has been shown to affect immune responses. In this thesis, data from five experimental studies have been collected to compare physiological and psychophysiological exercise responses between wheelchair athlete subgroups with different disabilities (tetraplegic, paraplegic, and non-spinal cord-injured). In two preparatory studies, physiological exercise responses to exhaustive (Chapter 4) and submaximal exercise (Chapter 5) were investigated in all three disability subgroups. Whilst reliability measures for peak oxygen uptake (VO2peak) were in a range observed previously in able-bodied athletes, the variation in tetraplegic athletes was larger when expressed relative to their VO2peak, questioning the use of this variable to track small changes in aerobic capacity in athletic populations. Submaximal physiological and psychophysiological exercise responses were found to be similar between disability subgroups when expressed as a percentage of VO2peak, justifying the protocol used in the laboratory study on mucosal immune function, which was based on the same percentages of VO2peak for all disability subgroups. The most extensive study of this thesis, detailed in Chapter 6, showed that single laboratory-controlled 60-min exercise sessions increase both salivary secretory immunoglobulin A (sIgA), a marker of mucosal immunity, and α-amylase, a marker of sympathetic activation in all three disability subgroups. However, the impaired sympathetic nervous system in tetraplegic athletes seemed to influence the fine-tuning of their sIgA response when compared with paraplegic and non-spinal cord-injured athletes, resulting in a larger exercise-induced increase of sIgA secretion rate when compared to paraplegic and non-spinal cord-injured athletes. Based on these results, the study detailed in Chapter 7 investigated sIgA responses in tetraplegic athletes during wheelchair rugby court training. Despite their disability, these athletes showed responses thought to be governed by the sympathetic nervous system, such as reductions of saliva flow rate as a result of strenuous exercise. Similarly, the responses observed in Chapter 8 imply a comparable trend of chronic sIgA exercise responses in tetraplegic athletes as found in the able-bodied population, namely a decrease in sIgA secretion rate during periods of heavy training. These are the first studies in wheelchair athlete populations to investigate mucosal immune responses. Interestingly, despite the disruption of their sympathetic nervous system, some responses in tetraplegic athletes are comparable with findings in able-bodied populations. It is possible that due to their highly trained nature, these tetraplegic individuals are able to compensate for their loss of central sympathetic innervation. This may be by way of adapted spinal reflex or parasympathetic nervous system activity, or increased sensitivity of receptors involved in autonomic pathways. Therefore, sympathetic nervous function in tetraplegic athletes may be qualitatively altered, but in parts still be functional.

Bifidobacterium infantis (BI) and other probiotics are non-pathogenic living organisms that have recently gained attention for their possible therapeutic implications on the health of the digestive tract. The mechanisms by which probiotics exert their effects are largely unknown. This study explored the protective and regulatory effect of oral BI on the enteric nervous system (ENS) in the TNBS-induced colitis rats. Electrical field stimulation and chemical stimulation by serotonin (5-HT) were used to elicit changes in the short-circuit current (Isc) response of the colonic rat tissue. BI-fed colitis rats expressed trends of higher secretomotor activity and revealed signs of decreased macroscopic inflammatory damage when compared to sham-fed colitis rats, suggesting a protective and preventative role of oral BI. These findings may provide additional insights for understanding the prophylactic and therapeutic value of specific probiotics in intestinal inflammatory disorders, offering the possibility of a noninvasive alternative to toxic and immune-compromising drugs. / Access to thesis permanently restricted to Ball State community only / Department of Physiology and Health Science

Central mechanisms involving aldosterone - mineralocorticoid receptor (MR) activation mediate the increase in sympathetic tone after myocardial infarction (MI). We hypothesized that an increase in cardiac sympathetic activity (CSA) post MI facilitates cardiac sympathetic axonal sprouting, and that central MR blockade attenuates CSA and reduces cardiac sympathetic hyperinnervation post MI. Western blotting and qRT-PCR were used to assess protein and gene expression, and fluorescent immunohistochemistry was used to study changes in sympathetic innervation. Tyrosine hydroxylase (TH) and Norepinephrine transporter protein content in the non-infarcted base of the heart remained unaltered. In contrast, protein gene product (PGP 9.5) protein was significantly increased 2 fold in the base of the heart, and 6 fold in the peri-infarct area at 1 wk post MI, and associated with increased ubiquitin expression. Cardiac myocytes rather than sympathetic axons were identified as the main source of elevated PGP 9.5 expression. At the infarct border sympathetic hyperinnervation was observed with a 4 fold increase in growth associated protein 43 (GAP 43), a 2 fold increase in TH and a 50% increase in PGP 9.5 positive fibers when compared to the epicardial side of the left ventricle in sham rats. Central infusion of the MR blocker eplerenone at 5 ug/day for 9 days post MI markedly attenuated the increase in TH, GAP 43 and PGP 9.5 nerve densities at the infarct border. Central MR blockade may attenuate sympathetic hyperinnervation by several mechanisms, including decreasing CSA post MI, or affecting expression or function of nerve growth factor protein. Marked PGP 9.5 expression occurs in cardiomyocytes early post MI, which may contribute to the increase in ubiquitin and the early cardiac remodeling post MI.

Additional appendix (5 p.) is pasted onto back end-paper. / Bibliography: leaves 219-244. / v, 244, [14] p., 67 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the complexity of the vagal reflexes arising from the upper gastrointestinal tract by recording single unit vagal afferents and efferents in the ferret. The potential involvement of various neurotransmitters in mediating and modulating gastrointestinal tract inputs is also explored. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999

Bibliography: leaves 282-354 / 354 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1986

Additional appendix (5 p.) is pasted onto back end-paper. Bibliography: leaves 219-244. Investigates the complexity of the vagal reflexes arising from the upper gastrointestinal tract by recording single unit vagal afferents and efferents in the ferret. The potential involvement of various neurotransmitters in mediating and modulating gastrointestinal tract inputs is also explored.

Asthma is a chronic inflammatory lung disease characterized by recurrent wheezing, coughing and difficulties in breathing. Asthma affects 25.7 million people in the USA including 8 million children. Asthma is often associated with early-life exposure to environmental insults. However, mechanisms that link early-life insults to persistent airway dysfunction are unknown. Our previous studies in mice showed that early-life allergen exposure increases the levels of neurotrophin 4 (NT4) causing airway smooth muscle (ASM) hyper innervation and persistent airway hyper reactivity (AHR). I show that early-life allergen exposure selectively increases cholinergic innervation. Notably, cholinergic nerves release acetylcholine, a potent airway constrictor that signals through the M3 receptor in ASM. Building upon these findings, my thesis encompasses two components. Firstly, how is NT4 expression aberrantly up regulated following early-life allergen exposure? Secondly, what is the effect of enhanced cholinergic innervation on the neonatal ASM? I find that NT4 is selectively expressed by ASM and mast cells in mice, nonhuman primates and humans. We show in mice that while NT4 expression in ASM remains unchanged upon allergen exposure, mast cells expand in number and degranulate to release NT4 thereby increasing NT4 levels in the lung. Adoptive transfer of wild-type mast cells, but not NT4-/- mast cells restores ASM innervation and AHR in KitW-sh/W-sh mice following early-life insults. In an infant primate model of asthma, the increased ASM innervation is also associated with the expansion and degranulation of mast cells. Therefore, pulmonary mast cells are a key source of aberrant NT4 expression following early-life insults in both mice and possibly primates. Next, I speculated that an increased cholinergic output in the neonatal lung might lead to persistent AHR. Using recurrent methacholine exposure and M3 receptor blocker, 4-DAMP, I show that enhanced cholinergic signaling in neonatal mice leads to persistent AHR without inflammation. In contrast, methacholine exposure in adult mice has no prolonged effects on airway reactivity. Together, my findings support a model in which deregulated neural activities following early-life insults cause persistent ASM hyper contractility. Thus, early-life interventions to block mast cell degranulation and the cholinergic pathway may benefit children with recurrent wheezing. / 2016-12-15T00:00:00Z

Quinze cabeças de tubarões Carcharias taurus (Rafinesque, 1810), pertencentes à Ordem Lamniformes e Família Odontaspididae, foram utilizadas para a realização desse estudo. O material destinado à análise foi obtido junto ao Terminal de Pesca de Santos, localizado em Santos, São Paulo, e descartado pelos pescadores por não apresentar valor comercial. A dissecação das cabeças visou caracterizar os músculos mandibulares, bem como descrever sua inervação realizada pelo ramo mandibular do nervo trigêmeo. Os músculos mandibulares de C. taurus são representados por: músculo pré-orbital, músculo levantador do palatoquadrado, músculo quadrado-mandibular e músculo intermandibular. O nervo trigêmeo de C. taurus origina-se em uma porção lateral da medula oblonga e ramifica-se na órbita para originar o ramo mandibular responsável pela inervação dos músculos derivados do arco mandibular. Os ramos proximais do ramo mandibular do nervo trigêmeo inervam o músculo levantador do palatoquadrado, o músculo pré-orbital e o músculo quadrado-mandibular recebem fibras dos ramos intermediários do ramo mandibular do nervo trigêmeo e a ramificação distal do mesmo é visualizada no músculo intermandibular. / During this study were used fifteen of Carcharias taurus (Rafinesque, 1810) (Odontaspididae, Lamniformes, Elasmobranchii) shark heads. The analised material was obteined in Terminal de Pesca de Santos, located in Santos, São Paulo. The material was descarded by the fishers because it hasn´t none comercial value. The heads dissection is foccated in the caracterization of the mandibular muscles and to discrebed the mandibular branch of the trigeminal nerve innervation as well. The C. taurus mandibular muscles are represented by: muscle pré-orbital, muscle levantador do palatoquadrado, muscle quadrado-mandibular and muscle intermandibular. The origin of the trimeginal nerve of C. taurus is located in a lateral portion of the medula oblonga. In the orbita it ramificates to originate de mandibular branch that inervates the muscles which is derived from the mandibular arch. The mandibular branch of the trigeminal nerve\'s proximal branches inervetes the muscle levantador do palatoquadrado, the muscles pré-orbitall and quadrado-mandibular receives fibers from the intermediate branches of the mandibular branch of the trigeminal nerve and the distal ramification of the mandibular branch are visualised in the muscle intermandibularis.

A facoemulsificação é, atualmente, considerada a técnica de eleição no tratamento da catarata, uma das principais causas de perda de visão, em cães. O procedimento demanda a realização de incisões na córnea para acesso à câmara anterior. Tais incisões, a despeito da extensão reduzida, podem lesar a inervação da córnea, comprometendo sua sensibilidade e, consequentemente, influenciar a produção lacrimal. Objetivando-se avaliar tais intercorrências, concebeu-se aferir a sensibilidade corneana e a produção lacrimal aquosa em cães submetidos à facoemulsificação. Para tanto, tais parâmetros foram investigados em 20 cães com idade, sexo, raça e peso variáveis. Os procedimentos cirúrgicos foram realizados em um único olho (OT), sendo o olho não operado utilizado como controle (OC). A sensibilidade da córnea foi mensurada com o estesiômetro de Cochet-Bonnet® e a produção lacrimal pelos testes do fenol vermelho e de Schirmer, em ambos os olhos. Os parâmetros foram aferidos previamente ao procedimento cirúrgico (M0 - valores basais) e, posteriormente, após sete dias (M1), 15 dias (M2), 30 dias (M3), 90 dias (M4) e 180 dias (M5). Os valores da produção lacrimal aferida com o teste do fenol vermelho, em M1, não diferiram dos obtidos previamente à cirurgia (M0), nos OT e OC; diferenças significativas foram observadas de M2 a M5, com valores superiores aos basais (M0), em ambos os olhos. Os resultados da mensuração lacrimal com o teste de Schirmer e da sensibilidade corneana à estesiometria (em cm e mm/g2) não diferiram dos basais (M0) em quaisquer dos períodos de avaliação (M1 a M5), em ambos os olhos. Os resultados obtidos ao estudo permitiram verificar que a realização da cirurgia de catarata por facoemulsificação, como fora proposto, não resulta em diminuição da sensibilidade corneana e produção lacrimal aquosa. / Phacoemulsification is considered the technique of choice for surgical extraction of cataracts, which is a leading cause of blindness in dogs. The procedure requires corneal incisions to enter the anterior chamber. These incisions, despite their reduced extensions, may damage the corneal innervation, compromising its sensitivity and, also, the tear production. Aiming to evaluate these consequences, this study intended to measure the corneal sensitivity and aqueous tear production in dogs undergoing phacoemulsification. These parameters were evaluated in 20 dogs, with different ages, genders, breeds and weights. Surgical procedures were performed in one eye (OT), and the fellow eye was used as a control (OC). Corneal sensitivity was measured with the Cochet-Bonnet® aesthesiometer and tear production by the phenol thread red test and Schirmer tear test, in both eyes. The parameters were measured prior to the surgery (M0 - baseline values) and after seven days (M1), 15 days (M2), 30 days (M3), 90 days (M4) and 180 days (M5). Tear production values measured with the phenol red test, in M1, were not different from the values measured prior to the surgery (M0), in OT and OC; significant differences were noticed from M2 to M5, with higher values when compared to baseline values (M0), in both eyes. Schirmer tear test and corneal sensitivity (in cm and mm/g2) values were not different from basal values (M0) in any of the evaluation times (M1 to M5), in both eyes. Our study outcomes suggest that phacoemulsification, as proposed previously, does not decrease the corneal sensitivity and aqueous tear production.

Central mechanisms involving aldosterone - mineralocorticoid receptor (MR) activation mediate the increase in sympathetic tone after myocardial infarction (MI). We hypothesized that an increase in cardiac sympathetic activity (CSA) post MI facilitates cardiac sympathetic axonal sprouting, and that central MR blockade attenuates CSA and reduces cardiac sympathetic hyperinnervation post MI. Western blotting and qRT-PCR were used to assess protein and gene expression, and fluorescent immunohistochemistry was used to study changes in sympathetic innervation. Tyrosine hydroxylase (TH) and Norepinephrine transporter protein content in the non-infarcted base of the heart remained unaltered. In contrast, protein gene product (PGP 9.5) protein was significantly increased 2 fold in the base of the heart, and 6 fold in the peri-infarct area at 1 wk post MI, and associated with increased ubiquitin expression. Cardiac myocytes rather than sympathetic axons were identified as the main source of elevated PGP 9.5 expression. At the infarct border sympathetic hyperinnervation was observed with a 4 fold increase in growth associated protein 43 (GAP 43), a 2 fold increase in TH and a 50% increase in PGP 9.5 positive fibers when compared to the epicardial side of the left ventricle in sham rats. Central infusion of the MR blocker eplerenone at 5 ug/day for 9 days post MI markedly attenuated the increase in TH, GAP 43 and PGP 9.5 nerve densities at the infarct border. Central MR blockade may attenuate sympathetic hyperinnervation by several mechanisms, including decreasing CSA post MI, or affecting expression or function of nerve growth factor protein. Marked PGP 9.5 expression occurs in cardiomyocytes early post MI, which may contribute to the increase in ubiquitin and the early cardiac remodeling post MI.