The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons.

Baroreflex Control of Heart Rate in Mice Overexpressing Human SOD1: Functional Changes in Central and Vagal Efferent Components.

Excessive reactive oxygen species (ROS) (such as the superoxide radical) are commonly associated with cardiac autonomic dysfunctions. Though superoxide dismutase 1 (SOD1) overexpression may protect against ROS damage to the autonomic nervous system, superoxide radical reduction may change normal physiological functions. Previously, we demonstrated that human SOD1 (hSOD1) overexpression does not change baroreflex bradycardia and tachycardia but rather increases aortic depressor nerve activity in response to arterial pressure changes in C57B6SJL-Tg (SOD1)2 Gur/J mice.

Deletion of TRPC6 Attenuates NMDA Receptor-Mediated Ca Entry and Ca-Induced Neurotoxicity Following Cerebral Ischemia and Oxygen-Glucose Deprivation.

Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na and Ca and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death.

Distribution and morphology of calcitonin gene-related peptide and substance P immunoreactive axons in the whole-mount atria of mice.

The murine model has been used to investigate the role of cardiac sensory axons in various disease states. However, the distribution and morphological structures of cardiac nociceptive axons in normal murine tissues have not yet been well characterized. In this study, whole-mount atria from FVB mice were processed with calcitonin gene-related peptide (CGRP) and substance P (SP) primary antibodies followed by secondary antibodies, and then examined using confocal microscopy.

Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus.

Large-conductance Ca2(+)-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7-9 days.

Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

Background: Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy.

Respiratory muscle pacing with chronically implanted intramuscular Permaloc electrodes: A feasibility study.

We tested the feasibility of stimulating upper-intercostal and abdominal muscles plus the diaphragm by using chronically implanted intramuscular electrodes.During two survival surgeries with six dogs, intramuscular electrodes were implanted bilaterally in the three respiratory muscles. Standard stimulation of the diaphragm was conducted.

Maternal diabetes increases large conductance Ca2+-activated K+ outward currents that alter action potential properties but do not contribute to attenuated excitability of parasympathetic cardiac motoneurons in the nucleus ambiguus of neonatal mice.

Previously, we demonstrated that maternal diabetes reduced the excitability and increased small-conductance Ca(2+)-activated K(+) (SK) currents of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA). In addition, blockade of SK channels with apamin completely abolished this reduction. In the present study, we examined whether maternal diabetes affects large-conductance Ca(2+)-activated K(+) (BK) channels and whether BK channels contribute to the attenuation of PCMN excitability observed in neonates of diabetic mothers.

Small conductance Ca2+-activated K+ channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus.

Small conductance Ca(2+)-activated K(+) channels (SK) regulate action potential (AP) firing properties and excitability in many central neurons. However, the functional roles of SK channels of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal days 7-9.

Maternal diabetes increases small conductance Ca2+-activated K+ (SK) currents that alter action potential properties and excitability of cardiac motoneurons in the nucleus ambiguus.

Parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) play a key role in regulating cardiac functions. In this study, we examined the effects of maternal diabetes on excitability, action potential (AP) properties, and small conductance Ca(2+)-activated K(+) (SK) currents of PCMNs. Neonatal mice from diabetic (OVE26 female, NMDM) and normal (FVB female, control) mothers that had been mated with nondiabetic fathers (FVB male) were used.

Structural remodeling of vagal afferent innervation of aortic arch and nucleus ambiguus (NA) projections to cardiac ganglia in a transgenic mouse model of type 1 diabetes (OVE26).

Diabetes-induced structural changes of vagal aortic afferent and cardiac efferent axons are not well understood. FVB control and OVE26 diabetic mice at different ages received injections of the tracer tetramethylrhodamine dextran (TMR-D) into the nodose ganglion to label vagal aortic afferents (at 3 and 6 months), or DiI injections into the nucleus ambiguus to label vagal cardiac efferents (at 3, 6, and 9 months). The aortic arch and atria were examined by using confocal microscopy.

Stimulating multiple respiratory muscles with intramuscular Permaloc electrodes.

Objective: To test the feasibility of implanting intramuscular electrodes (Permaloc, Synapse Biomedical Inc, Oberlin OH) with self-securing polypropylene anchors to stimulate upper-intercostal and abdominal muscles plus the diaphragm.

Methods/results: In 6 anesthetized dogs, 12 Permaloc electrodes were implanted in the 3 respiratory muscles (4 in each muscle group). Tidal volume with diaphragmatic stimulation was 310 +/- 38 mL (mean +/- SE); with upper intercostal stimulation, it was 68 +/- 18 mL; and with combined diaphragm intercostal stimulation, it was 438 +/- 78 mL.

Impairment of baroreflex control of heart rate and structural changes of cardiac ganglia in conscious streptozotocin (STZ)-induced diabetic mice.

Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model.

Effects of electrical stimulation and gonadal steroids on rat facial nerve regenerative properties.

Purpose: The neurotherapeutic effects of nerve electrical stimulation and gonadal steroids have independently been demonstrated. The purpose of this study was to investigate the therapeutic potential of a combinatorial treatment strategy of electrical stimulation and gonadal steroids on peripheral nerve regeneration.

Methods: Following a facial nerve crush axotomy in gonadectomized adult male rats, testosterone propionate (TP), dihydrotestosterone (DHT), or estradiol (E(2)) was systemically administered with/without daily electrical stimulation of the proximal nerve stump.

Balloon-tipped catheter for measuring urethral pressures.

Background: Better methods are needed for recording urethral function for complex urologic problems involving the bladder, urethra, and pelvic floor.

Objective: To evaluate a balloon catheter for recording urethral pressure and function using bench-top testing and evaluation in an animal model.

Methods: Balloon pressure-recording methods included slightly inflating the balloon with water and placing the pressure transducer on the distal end of the catheter.

Impairment of baroreflex control of heart rate in conscious transgenic mice of type 1 diabetes (OVE26).

Baroreflex control of heart rate (HR) is impaired in human type 1 diabetes mellitus. The goal of this study is to use a transgenic mouse model of type 1 diabetes (OVE26) to assess the diabetes-induced baroreflex impairment in the conscious state. OVE26 transgenic mice (which develop hyperglycemia within the first three weeks after birth due to the specific damage of beta cells) and normal control mice (FVB) 5-6months of age were anesthetized, and the left femoral artery and both veins were catheterized.

Diabetes induces neural degeneration in nucleus ambiguus (NA) and attenuates heart rate control in OVE26 mice.

Baroreflex sensitivity is impaired by diabetes mellitus. Previously, we found that diabetes induces a deficit of central mediation of baroreflex-mediated bradycardia. In this study, we assessed whether diabetes induces degeneration of the nucleus ambiguus (NA) and reduces heart rate (HR) responses to l-Glutamate (L-Glu) microinjection into the NA.

Nitric oxide and carbon monoxide synthesizing enzymes and soluble guanylyl cyclase within neurons of adult human cardiac ganglia.

Nitric oxide and carbon monoxide are diffusible gas messengers, synthesized by nitric oxide synthase or heme oxygenase 2, respectively, that can activate soluble guanylyl cyclase in adjacent cells. Nitric oxide and carbon monoxide neuromodulation in cardiac ganglia has been demonstrated. However, identification of nitric oxide or carbon monoxide in human cardiac ganglia needs to be confirmed as suggested from animal model studies.

Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguous of F344 rats.

Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the nucleus ambiguous (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3-4 mo) were exposed to room air (RA) or CIH for 35-50 days (n = 18/group).

Effective methods of pelvic plexus nerve and bladder stimulation in anesthetized animal model.

Urinary retention is a serious urological problem associated with spinal cord injuries (SCIs) and other pelvic disorders. Effective methods of pelvic nerve stimulation were investigated for this problem. Following anesthesia in five dogs, the bladder was surgically exposed.

Electrical stimulation facilitates rat facial nerve recovery from a crush injury.

Objective: To study the effect of electrical stimulation on accelerating facial nerve functional recovery from a crush injury in the rat model.

Study Design: Experimental.

Method: The main trunk of the right facial nerve was crushed just distal to the stylomastoid foramen, causing right-sided facial paralysis in 17 Sprague-Dawley rats.

Accelerating functional recovery after rat facial nerve injury: Effects of gonadal steroids and electrical stimulation.

Objective: We investigated the combined effects of electrical stimulation and testosterone propionate on overall recovery time in rats with extracranial crush injuries to the facial nerve.

Study Design: Male rats underwent castration 3 to 5 days prior to right facial nerve crush injury and electrode implantation. Rats were randomly assigned to two groups: crush injury + testosterone or crush injury with electrical stimulation + testosterone.

Structural remodeling of nucleus ambiguus projections to cardiac ganglia following chronic intermittent hypoxia in C57BL/6J mice.

The baroreflex control of heart rate (HR) is reduced following chronic intermittent hypoxia (CIH). Since the nucleus ambiguus (NA) plays a key role in baroreflex control of HR, we examined whether CIH remodels vagal efferent projections to cardiac ganglia. C57BL/6J mice (3-4 months of age) were exposed to either room air (RA) or CIH for 3 months.

Chronic suppressive therapy with calcium channel antagonists for refractory meningiomas.

In this article, the authors review the research supporting the use of calcium channel antagonists (CCAs) in the treatment of recurrent or unresectable meningiomas. Calcium channel antagonists (for example, diltiazem and verapamil) are known to augment the effects of chemotherapy drugs (for example, vincristine) in multiple cancers. Although it was initially thought that this occurred by interference with calcium-dependent secondary messenger systems, it appears that other mechanisms account for this effect.

Microstimulators and intramuscular hook electrodes for the stimulation of respiratory muscles.

Background/objectives: We determined the feasibility of stimulating the major muscles of respiration with different types of electrodes. Intramuscular hook electrodes, model microstimulators (M-Micro) developed in our laboratory, and commercial radiofrequency microstimulators (RFM) (Alfred Mann Foundation, Valencia, CA), were employed in this investigation.

Methods: In 8 anesthetized dogs, M-Micro were placed bilaterally on the diaphragm and in the abdominal muscles, and hook electrodes were placed in the 3rd and 5th intercostal regions adjacent to the intercostal nerves known to support inspiration.