scholarly journals Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen

2021 ◽  
Vol 15 ◽  
Author(s):  
Cindy G. J. Cleypool ◽  
David J. Brinkman ◽  
Claire Mackaaij ◽  
Peter G. J. Nikkels ◽  
Martijn A. Nolte ◽  
...  
Keyword(s):  
T Cells ◽  
Sympathetic Nerve ◽  
Close Association ◽  
Sympathetic Innervation ◽  
Sympathetic Nerves ◽  
Human Spleen ◽  
Related Variation ◽  
Age Related ◽  
Splenic Parenchyma ◽  
Anti Inflammatory

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution.Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures.Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves.Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.

Pharmacological analysis of sympathetic function in the embryonic chick heart

1977 ◽  
Vol 232 (3) ◽  
pp. R116-R123
Author(s):  
N. G. Culver ◽  
D. A. Fischman
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Innervation ◽  
Sympathetic Nerves ◽  
Nerve Function ◽  
Embryonic Chick ◽  
Neuronal Function ◽  
In Ovo ◽  
Sympathetic Function ◽  
Chick Heart ◽  
Embryonic Chick Heart

Sympathetic nerve cells enter the embryonic chick heart on the fifth day in ovo, but it is uncertain when these nerves become functional. Using pharmacological probes known to affect the embryonic circulation, sympathetic nerve function was examined at various stages of development. Exogenous norepinephrine elicited cardioacceleration in the hearts of embryos with intact extraembryonic circulation both before (stage 20-24) and after (stage 28-32) sympathetic innervation of the heart, and this acceleration could be inhibited by propranolol and practolol. In contrast, ganglionic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) elicited cardioacceleration only after stages 27-28 (i.e., after sympathetic innervation), producing a 25-30% increase in heart rate over the predrug levels of 148.7 +/- 1.8 beats/min. DMPP-elicited positive chronotropy was reduced by beta-receptor antagonists, hexamethonium, guanethidine (GuE), and tetrodotoxin. In preparations of the embryonic thorax in which the innervated heart was separated from brain and adrenal influences, DMPP elicited a GuE-sensitive cardioacceleration. It is concluded that during chick embryonic development, no more than a 1-day interval exists between the appearance of sympathetic nerves in the heart and the onset of neuronal function in that organ.

AGE-RELATED VARIATION IN PROPORTION OF CIRCULATING T CELLS

The Lancet ◽  
1974 ◽  
Vol 304 (7886) ◽  
pp. 922-924 ◽  
Author(s):  
MarilynA. Smith ◽  
Judith Evans ◽  
C.M. Steel
Keyword(s):  
T Cells ◽  
Related Variation ◽  
Age Related ◽  
Circulating T Cells

scholarly journals Animal aging and regulation of sympathetic nerve discharge

2010 ◽  
Vol 109 (4) ◽  
pp. 951-958 ◽  
Author(s):  
Michael J. Kenney
Keyword(s):  
Animal Models ◽  
Sympathetic Nerve ◽  
Animal Studies ◽  
Current Knowledge ◽  
Human Subjects ◽  
Sympathetic Nerves ◽  
Age Related ◽  
Current Knowledge Base ◽  
Age Related Changes ◽  
Nerve Discharge

Studies completed in human subjects have made seminal contributions to understanding the effects of age on sympathetic nervous system (SNS) regulation. Numerous experimental constraints limit the design of studies involving human subjects; therefore, completion of studies in animal models of aging would be expected to provide additional insight regarding mechanisms mediating age-related changes in sympathetic nerve discharge (SND) regulation. The present review assesses the current state of the literature regarding contributions from animal studies on the effects of advancing age on SND regulation, focusing primarily on studies that have used direct recordings of sympathetic nerve outflow. Few studies using direct SND recordings have been completed in animal models of aging, regardless of the fundamental component of SND regulation reviewed (basal levels, acute responsiveness, relationships between the discharges in sympathetic nerves, central neural regulation). SNS responsiveness to various acute stressors is altered in aged compared with young animals; however, mechanisms remain virtually unexplored. There is a marked dearth of studies that have used central neural microinjection techniques in conjunction with SND recordings in aged animals, making it difficult to develop an evidence-based framework regarding potential age-associated effects on central regulation of SND. Determination of age-related changes in mechanisms regulating SND is important for understanding relationships between chronic disease development and changes in SNS function; however, this can only be achieved by substantially extending the current knowledge base regarding the effects of age on SND regulation in animal studies.

Abstract 306: Sympathetic Reinnervation is Required for Mammalian Cardiac Regeneration.

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Ian A White ◽  
Julie Gordon ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Sympathetic Innervation ◽  
Cardiac Regeneration ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Scar Tissue ◽  
Neonatal Mouse ◽  
Autonomic Nerves ◽  
Mouse Heart ◽  
Age Related ◽  
Innate Ability

Rationale: Established animal models of limb and tissue regeneration with re-vascularization demonstrate a critical dependence on concurrent reinnervation by the peripheral nervous system. Objective: Considering the significant abundance of autonomic nerves in the mammalian heart we tested the hypothesis that reinnervation is required for neonatal mouse cardiac regeneration. Methods and Results: Crossing Wnt1:cre transgenic mice with a double-tandem (td) tomato reporter strain identifies all neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. Whole mount epi-fluorescence microscopy facilitated the clear resolution of subepicardial autonomic nerves in the mouse ventricles providing unprecedented detail of the subepicardial neuroanatomy of the mouse heart. Sympathetic nerve bundles envelop the entire heart and extend to the tip of the ventricular apex. Our data demonstrate that during regeneration of the resected ventricular apex of the neonatal mouse heart, sympathetic nerves fibers undergo concurrent re-growth into the injury site resulting in complete sympathetic reinnervation of the regenerated tissue. Sympathectomy of the heart, induced by administration of 6-OHDA, was sufficient to block innate cardiac regeneration in the neonatal mouse. Conclusions: We report that the innate ability of the neonatal mouse heart to undergo regeneration in response to injury is dependent on sympathetic innervation of the ventricular myocardium. Ablation of post-ganglionic sympathetic nerves blocks the innate regenerative capacity of neonatal mouse hearts suggesting that sympathetic reinnervation is critical for ventricular regeneration. This finding has significant implications for adult regeneration following myocardial infarction where nerve growth is hindered by age related influences and scar tissue.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

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