Brainstem and Cranial Nerves: Longitudinal Pathways of the Brainstem

This chapter reviews pathways that are not at a single level of the brainstem but rather involve multiple areas with supratentorial input. The chapter highlights autonomic pathways, the reticular formation and chemically defined groups, and coordination of eye movements. Sympathetic fibers travel from the hypothalamus to the intermediolateral column in the spinal cord through the lateral brainstem. Patients with a unilateral lesion of the lateral brainstem may have ipsilateral Horner syndrome. The ventrolateral medulla, also a sympathetic region of the brainstem, projects to the spinal cord and is involved in the innervation of blood vessels in the limbs.

The Effect of Castration on Peripheral Autonomic Neurons Supplying Mammalian Male Genitourinary System

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed.

Autonomic and cholinergic mechanisms mediating cardiovascular and temperature effects of donepezil in conscious mice

Donepezil is a centrally-acting acetylcholinesterase (AChE) inhibitor with therapeutic potential in inflammatory diseases; however, the underlying autonomic and cholinergic mechanisms remain unclear. Here, we assessed effects of donepezil on mean arterial pressure (MAP), heart rate (HR), HR variability, and body temperature in conscious adult male C57BL/6 mice to investigate the autonomic pathways involved. Central vs. peripheral cholinergic effects of donepezil were assessed using pharmacological approaches including comparison with the peripherally-acting AChE inhibitor, neostigmine. Drug treatments included donepezil (2.5 or 5 mg/kg s.c.), neostigmine methyl sulfate (80 or 240 μg/kg i.p.), atropine sulfate (5 mg/kg i.p.), atropine methyl bromide (5 mg/kg i.p.), or saline. Donepezil, at 2.5 and 5 mg/kg, decreased HR by 36±4 and 44±3% compared to saline (n=10, P<0.001). Donepezil, at 2.5 and 5 mg/kg, decreased temperature by 13±2 and 22±2% compared to saline (n=6, P<0.001). Modest (P<0.001) increases in MAP were observed with donepezil after peak bradycardia occurred. Atropine sulfate and atropine methyl bromide blocked bradycardic responses to donepezil, but only atropine sulfate attenuated hypothermia. The pressor response to donepezil was similar in mice co-administered atropine sulfate; however, co-administration of atropine methyl bromide potentiated the increase in MAP. Neostigmine did not alter HR or temperature but did result in early increases in MAP. Despite the marked bradycardia, donepezil did not increase normalized high frequency HR variability. We conclude that donepezil causes marked bradycardia and hypothermia in conscious mice via activation of muscarinic receptors while concurrently increasing MAP via autonomic and cholinergic pathways that remain to be elucidated.

The Subnuclear Distribution of 5-HT1A Receptors in the Human Nucleus of the Solitary Tract and Selected Structures of the Caudal Medulla

The distribution of 5-HT1A receptors in the subnuclei of the human caudal nucleus of solitary tract and adjacent structures in the dorsal vagal complex was studied using [3H]8-OH-DPAT, a highly selective 5-HT1A receptor agonist. The highest binding of the labeled ligand was found in the dorsal motor nucleus of the vagus, followed by the medial, intermediate, and subpostremal subnuclei of the nucleus of solitary tract. Previous animal studies suggest an important role for these structures in the regulation of visceral function, particularly for the gastrointestinal and cardiovascular systems. The results of this study suggest the possibility of an analogous role for 5-HT1A receptors in the regulation of these autonomic pathways in humans as well.

Central Command and the Regulation of Exercise Heart Rate Response in Heart Failure with Preserved Ejection Fraction

Background: Chronotropic incompetence (CI) is common in HFpEF and is linked to impaired aerobic capacity. Whether upstream autonomic signaling pathways responsible for raising exercise heart rate (HR) are impaired in HFpEF is unknown. We investigated the integrity of central command and muscle metaboreceptor function, two predominant mechanisms responsible for exertional increases in HR, in HFpEF and senior control subjects. Methods: Fourteen healthy, senior controls (7M,7F) and 20 carefully screened HFpEF patients (8M,12F) underwent cardiopulmonary exercise testing (peak VO 2 ) and static handgrip exercise at 40% of maximal voluntary contraction (MVC) to fatigue with post-exercise circulatory arrest (PECA) for 2 minutes to assess central command and metaboreceptor function respectively. Results: Peak VO 2 (13.1 ± 3.4 vs 22.7 ± 4.0 ml/kg/min; p<0.001) and HR (122 ± 20 vs 155 ± 14 bpm; p<0.001) were lower in HFpEF than senior controls. There were no significant differences in peak HR response during static handgrip between groups (HFpEF vs controls: 90 ± 13 vs 93 ± 10 bpm; p=0.49). Metaboreceptor function defined as mean arterial blood pressure at the end of PECA was also not significantly different between groups. Conclusions: Central command (vagally mediated) and metaboreceptor function (sympathetically mediated) in patients with HFpEF were not different from healthy senior controls despite significantly lower peak whole-body exercise heart rates. These results demonstrate key reflex autonomic pathways regulating exercise heart rate responsiveness are intact in HFpEF.