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W W Blessing

Publications and source records attributed to W W Blessing.

At least 55 records · Page 3Linked to original sources
PubMed1997

Inadequate frameworks for understanding bodily homeostasis.

Separate nervous systems, somatic and autonomic, were proposed to regulate the portion of the individual's life that is concerned with the external environment and the portion that is concerned with internal homeostasis. Regulation of the autonomic system by the CNS was assigned to the limbic system. Brainstem circuitry, between limbic and autonomic systems, was assigned to the supposedly nonspecific reticular formation. In fact, daily survival depends on integrated control of behavior and internal physiology. In mammals only the brain has the inbuilt programming for patterned co-ordination of these activities. The terms autonomic nervous system, limbic system and reticular formation are at odds with this patterned co-ordination. They should be abandoned and replaced with the term visceral neurons (afferent and efferent) and with reference to relevant specific-neural circuitry in the brain.

Animals↗
PubMed1997

Cutaneous vasoconstriction in conscious rabbits during alerting responses detected by hippocampal theta-rhythm.

We determined whether alerting stimuli cause cutaneous vasoconstriction in conscious rabbits. We compared ear blood flow with renal, mesenteric, and femoral flows at rest and in response to nonnoxious alerting stimuli, which induced theta-rhythm (4-9 Hz) in the simultaneously recorded hippocampal electroencephalogram (EEG). theta-Inducing stimuli (e.g., whistles and fur touches) reduced ear flow by 95 +/- 6%, commencing 1-2 s after the EEG change and lasting 45 s. Renal flow did not significantly change with alerting stimuli, mesenteric and femoral flows slightly decreased, arterial pressure transiently rose (+10 +/- 3 mmHg), and heart rate fell (+43 +/- 9 beats/min). At rest, the coefficient of variation for ear flow (62 +/- 6%) was greater than for other flows (P < 0.01). Phentolamine (1 mg/kg iv) reduced this coefficient to 29 +/- 4% (P < 0.01). Our study demonstrates that alerting responses in conscious rabbits are associated with selective cutaneous vasoconstriction, without increase in flow to skeletal muscle.

Adrenergic alpha-Antagonists↗
PubMed1996

Nitric oxide synthesising neurons in the central subnucleus of the nucleus tractus solitarius in humans.

The central subnucleus of the nucleus tractus solitarius is an important central structure mediating esophago-esophageal reflexes. In experimental animals it contains a discrete group of nitric oxide synthase (NOS) neurons. The central subnucleus has not been described in the human. In the present study we mapped the distribution of NO synthesising neurons in the human nucleus tractus solitarius, using the NADPH diaphorase reaction and an antibody against NOS. We found a distinct group of small ovoid NO synthesising neurons, dorsomedial to the solitary tract and ventral to the gelatinous subnucleus, extending from 1 to 5 mm rostral to the obex, thus corresponding closely to the central subnucleus in experimental animals. Our study defines the anatomical location of the central subnucleus in the human nucleus tractus solitarius, and suggests the possible involvement of nitric oxide in the central regulation of esophageal reflexes in humans.

Aged↗
PubMed1996

Preganglionic parasympathetic salivatory neurons in the brainstem contain markers for nitric oxide synthesis in the rabbit.

The present study investigated the possible presence of markers for nitric oxide synthesis in brainstem preganglionic parasympathetic neurons involved in control of the submandibular and sublingual salivary glands of rabbits and rats. Retrograde axonal tracing was performed with biotinylated dextran to identify preganglionic parasympathetic salivatory neurons and combined with NADPH diaphorase histochemistry or nitric oxide synthase immunohistochemistry. The results of the double-labelling experiments demonstrated that most of the retrogradely labelled preganglionic parasympathetic neurons in rabbits contained the markers for nitric oxide synthesis, whereas, in rats most retrogradely labelled neurons lacked the markers for nitric oxide synthesis. These observations suggest that nitric oxide could influence ganglionic transmission in parasympathetic pathways controlling salivary secretion in the rabbit, but not in the rat.

Animals↗
PubMed1996

Microtubule-associated protein 5 is a component of Lewy bodies and Lewy neurites in the brainstem and forebrain regions affected in Parkinson's disease.

Ubiquitin-positive Lewy neurites and Lewy bodies are found in idiopathic Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). We found that, in three patients with PD and one with DLBD, microtubule-associated protein 5 (MAP5) immunostaining was consistently present in both Lewy neurites and Lewy bodies throughout the brainstem and forebrain regions affected in the disease. In contrast, other cytoskeletal markers (neurofilaments and MAP2) could be demonstrated in only a small fraction of Lewy bodies and neurites. Confocal microscopy demonstrated that MAP5 immunolabeling was located around the perimeter of the ubiquitin-positive labeling which occupied the central region of the neurite and Lewy body, with some overlap between MAP5 and ubiquitin staining. In contrast, in those Lewy bodies and neurites immunopositive for phosphorylated and non-phosphorylated neurofilament proteins, the neurofilament labeling was quite peripheral to the ubiquitin staining, with little or no overlap. Our results suggest MAP5 is more closely associated with the ubiquitinated proteins of Lewy bodies and neurites than other cytoskeletal proteins.

Aged↗
PubMed1996

Human brainstem preganglionic parasympathetic neurons localized by markers for nitric oxide synthesis.

Identification of human parasympathetic preganglionic neurons in pontomedullary regions has been largely based on studies using cholinesterase histochemical procedures, and so far there is no adequate account of the location of these cells. Nitric oxide synthase (NOS) is present in brainstem parasympathetic preganglionic salivatory neurons in the rabbit (Zhu et al., 1996). In the present study we have used histochemical and immunohistochemical staining for NOS to examine possible preganglionic parasympathetic neurons in the human brainstem. We examined, in five human brains, the distribution, through the caudal pons and rostral medulla, of NOS-positive neurons in serial sections stained with NADPH diaphorase for histochemistry, and with antibodies against neuronal NOS peptide for immunohistochemistry. In scattered pontomedullary regions (rostral to the dorsal motor nucleus and the nucleus ambiguus) known to contain parasympathetic preganglionic neurons in animals, we observed groups of NOS-positive neurons which correspond in morphology and distribution with NOS-positive parasympathetic preganglionic neurons in rabbits. These neurons are probably parasympathetic preganglionic neurons in the human brainstem, involved in the control of lacrimation, salivation, oral and nasopharyngeal secretion, as well as the control of the dilation of extra- and intracranial blood vessels.

Aged↗
PubMed1996

Continuous measurement of changes in internal carotid and vertebral arterial blood flow with chronically implanted ultrasonic Doppler probes in anesthetized and conscious rabbits.

Chronically implanted ultrasonic Doppler flowmeters were used to obtain simultaneously recorded flow velocity signals from internal carotid and vertebral arteries, and the sagittal sinus, in rabbits. All three signals increased to 144 +/- 7-215 +/- 35% of baseline during hypercapnia (arterial Pco2 55 mmHg) in both anesthetized and conscious animals. During the period of change in inspired CO2, the relationship between simultaneously recorded mean internal carotid and mean sagittal sinus signals was linear, with the correlation ranging from 0.83 to 0.96. Since forebrain arterial inflow must approximate forebrain venous outflow, the high correlation between internal carotid and sagittal sinus signals indicates that these measures provide reliable and valid indices of cerebral blood flow (CBF). Vertebral and internal carotid angiography confirmed the location of Doppler probe. Chronically implanted ultrasonic Doppler flowmeters can, thus, provide continuous noninvasive measurements of cerebral arterial flow in both anesthetized and conscious rabbits.

Anesthesia↗
PubMed1995

Nitric oxide-synthesising neurons in the central subnucleus of the nucleus tractus solitarius provide a major innervation of the rostral nucleus ambiguus in the rabbit.

We describe an intramedullary nitric oxide synthase (NOS) neural pathway that projects from the nucleus tractus solitarius (NTS) to the rostral nucleus ambiguus (NA) in the rabbit. With the use of NADPH diaphorase histochemistry and NOS immunohistochemistry, a compact group of NOS-positive perikarya was identified in the central subnucleus of the NTS dorsomedial to the tractus solitarius and rostral to the obex. A dense network of NOS terminals was seen in the rostral NA. We investigated whether NOS terminals in the NA derive from NOS perikarya in the central NTS and whether the central NOS pathway links esophageal afferents and efferents. In some rabbits, the central NTS was unilaterally lesioned. In others, Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected into the central NTS, or cholera toxin-gold was injected into the NA, or cholera toxin-horseradish peroxidase (HRP) was injected into the wall of the esophagus. The medulla was subsequently processed to demonstrate PHA-L, cholera toxin-gold, HRP, and NOS reactivity. Seven days after the NTS lesion, we observed a marked decrease in the density of NOS terminals in the ipsilateral NA. After injection of PHA-L into the central NTS, a dense group of PHA-L fibres was seen in the rostral NA, principally ipsilaterally. Afferent fibres from the esophagus were found around the NOS cell bodies in the central NTS, and many of these NOS neurons were double labeled with cholera toxin-gold after injection of this tracer into the NA. NOS terminals were found around NA neurons that were retrogradely labelled from the esophagus. We conclude that the NOS neurons in the central NTS act as interneurons in a central pathway connecting esophageal afferents and efferents.

Amino Acid Oxidoreductases↗
PubMed1995

Fos-determined distribution of neurons activated during the Bezold-Jarisch reflex in the medulla oblongata in conscious rabbits and rats.

Experiments were performed in unanaesthetized rabbits and rats to investigate the distribution, within the medulla oblongata, of neurons activated during the Bezold-Jarisch reflex. Repeated intravenous injections of phenylbiguanide evoked depressor and bradycardic responses in both rabbits and rats. Fos-positive neurons were present in the nucleus tractus solitarius and in the caudal ventrolateral medulla oblongata. Double-label tyrosine hydroxylase (TH) immunohistochemical studies in the ventrolateral medulla showed that most Fos-positive neurons in the caudal ventrolateral medulla were TH-negative neurons scattered between A1 noradrenaline cells, in the rabbit and in the rat. Approximately 20% of neurons in the caudal ventrolateral medulla in rabbits, and 50% in rats, were immunoreactive for both Fos and TH. Some Fos-positive, TH-negative neurons in the caudal ventrolateral medulla were retrogradely labelled with cholera toxin B-Gold after injection of this tracer into the sympathoexcitatory region of the rostral ventrolateral medulla. Our data suggests that neurons in the nucleus tractus solitarius, and rostrally projecting TH-negative neurons in the caudal ventrolateral medulla, are part of the pathway by which stimulation of cardiopulmonary receptors inhibits sympathetic vasomotor tone to decrease blood pressure during the Bezold-Jarisch reflex.

Animals↗
PubMed1995

Herpes simplex virus induces Fos expression in rat brainstem neurons.

After the injection of Herpes Simplex Virus type 1 into the rat cervical vagus nerve, transneuronally labelled virus-containing neurons and glial cells were present in the medulla oblongata. Fos-containing nuclei were present in the same regions of the brain. A double-labelling procedure revealed that most of the virus-positive neurons also contained Fos-positive nuclei. Appearance of HSV1 antigen within the CNS is associated with Fos expression in neurons and glial cells.

Animals↗
PubMed1995

Abdominal vagal stimulation excites bulbospinal barosensitive neurons in the rostral ventrolateral medulla.

We used extracellular recordings to examine the central pathway whereby electrical stimulation of abdominal vagal afferents elevates arterial pressure in the rabbit. Bulbospinal neurons in the rostral ventrolateral medulla were identified by antidromic activation from the dorsolateral funiculus of the thoracic spinal cord. Their barosensitivity was assessed by their response to intravenous phenylephrine and by their cardiac cycle-related rhythmicity. We used peristimulus histogram procedures to assess the effect of electrical stimulation of abdominal vagal afferents on the discharge rate of these neurons. Electrical stimulation (one to three pulses) activated 98 of 123 neurons tested (80%), had no effect on 22 neurons (18%) and inhibited the remaining three neurons. Latency to peak excitation was 228 +/- 3 ms, indicating that the conduction velocity of the vagal afferents was about 0.6 m/s, in the unmyelinated fibre range. Lower oesophageal distension with a balloon excited 22 of 48 neurons (46%), inhibited 12 neurons (25%) and had no effect on the remaining 14 cells (29%). Vagally induced excitation was reduced by aortic depressor nerve stimulation in nine of 13 neurons. Lightly touching the animal's back and legs had no effect on 56 of 60 neurons. Nociceptive stimuli failed to affect 47 of 60 neurons tested. No excitation was seen with electrical stimulation of the sciatic or central ear nerves. Our study identifies a robust excitatory input from the abdominal vagus to bulbospinal barosensitive neurons in the rostral ventrolateral medulla. Relevant physiological stimuli include lower oesophageal distension. The pathways may be relevant to cardiovascular changes which accompany upper gastrointestinal function.

Abdomen↗
PubMed1995

Ubiquitin-positive degenerating neurites in the brainstem in Parkinson's disease.

Characteristic ubiquitin-positive, tau-negative, degenerating neurites were present in brainstem regions known to be involved in idiopathic Parkinson's disease. Corresponding changes were entirely absent from controls and from the brainstems obtained from patients who had died with Alzheimer's disease, motor neuron disease and multiple system atrophy. In Parkinson's disease cases degenerating neurites were particularly striking in the dorsal motor nucleus of the vagus. In this nucleus the density of degenerating neurites was inversely related to the duration of Parkinson's disease symptoms. Some ubiquitin-positive degenerating neurites also contained neurofilament immunoreactivity. However, confocal microscopy revealed that ubiquitin and neurofilament reactivities were located in separate regions of the degenerating neurite, suggesting that proteins other than neurofilaments may be important in the process of ubiquitination. The demonstration of ubiquitin-positive degenerating neurites in routinely prepared paraffin-embedded material, particularly in the dorsal motor nucleus of the vagus, could become diagnostically useful in those Parkinson's disease cases in which Lewy bodies are difficult to find. Demonstration of extensive ubiquitin-positive degenerating neurites might provide a clue to disease activity at the time of death.

Aged↗
PubMed1994

Vasoconstriction induced by inhalation of irritant vapour is associated with appearance of Fos protein in C1 catecholamine neurons in rabbit medulla oblongata.

The medulla oblongata was examined with Fos and tyrosine hydroxylase (TH) immunohistochemistry after 2 h of intermittent nasopharyngeal stimulation with formaldehyde vapour in the conscious rabbit. The stimulation caused apnoea, bradycardia and a rise in blood pressure known to be associated with vigorous vasoconstriction. Fos-positive neurons occurred in the spinal trigeminal nucleus, the nucleus tractus solitarius, the raphe nuclei and the ventrolateral medulla. In the rostral ventrolateral medulla, 68% of the Fos-positive neurons were TH-positive C1 cells. Our data indicate that nasopharyngeally-evoked peripheral vasoconstriction is associated with activation of C1 neurons.

Administration, Inhalation↗
PubMed1994

Fos-containing neurons in medulla and pons after unilateral stimulation of the afferent abdominal vagus in conscious rabbits.

Vagal afferents originating in abdominal viscera initiate numerous centrally-mediated responses, including behavioural, cardiovascular and hormonal changes associated with satiety, and nausea and vomiting. The present work was undertaken to map the pontomedullary distribution of neurons expressing Fos immunoreactivity following unilateral electrical stimulation of abdominal vagal afferents in conscious unanaesthetized rabbits. After 2 h of stimulation of the anterior trunk of the abdominal vagus nerve (20 Hz, 0.5 mA, 0.5 ms duration, 4.5 min on, 0.5 min off), Fos-positive neurons were found in the area postrema, the nucleus tractus solitarius, the spinal nucleus of the trigeminal nerve, the caudal and the rostral ventrolateral medulla, the locus coeruleus, the subcoeruleus and the lateral parabrachial nucleus. In all these regions, more than 70% of Fos-containing neurons occurred on the ipsilateral side. In control animals only occasional Fos-immunoreactive neurons were observed, usually very faintly labelled. Simultaneous staining for both Fos and tyrosine hydroxylase revealed Fos immunoreactivity in catecholamine neurons, including A1, A2, C1, A5, subcoeruleus and locus coeruleus (A6) groups. Our findings complement functional studies in the rabbit, identifying A1 neurons as part of the central pathway by which afferent abdominal vagal stimulation increases plasma vasopressin, and C1 neurons as part of the central pathway, whereby afferent abdominal vagal stimulation increase arterial pressure.

Afferent Pathways↗
PubMed1994

Loss of non-phosphorylated neurofilament immunoreactivity, with preservation of tyrosine hydroxylase, in surviving substantia nigra neurons in Parkinson's disease.

The distribution of neurofilament immunoreactivity in the substantia nigra was examined by immunohistochemistry in five patients dying with Parkinson's disease and six control patients dying without neurological disease. In controls, pigmented neurons in the substantia nigra were intensively labelled by SMI32, a monoclonal antibody to non-phosphorylated neurofilament protein. In the substantia nigra from patients who had Parkinson's disease, there was a pronounced reduction of SMI32 labelling intensity in surviving pigmented neurons. By contrast, tyrosine hydroxylase immunoreactivity in surviving pigmented neurons was normal. SMI32 labelling was normal in regions of the brainstem not affected by the neuropathological process of Parkinson's disease. Findings with either antibodies to phosphorylated neurofilament, or enzymatic dephosphorylation followed by SMI32 labelling, indicated that loss of SMI32 immunostaining in Parkinson's disease was not due to masking of the neurofilament epitopes by phosphorylation. Our results indicate that neurofilament proteins are particularly likely to be disrupted or destroyed by the neuropathological process of Parkinson's disease. Nevertheless, the normal appearance of tyrosine hydroxylase indicates that protein synthesising systems may be intact in surviving neurons. Loss of neurofilament immunoreactivity may prove a sensitive neuropathological marker for characterisation of degenerating neurons in Parkinson's disease.

Aged↗
PubMed1994

Vasopressin secretion after stimulation of abdominal vagus in rabbit: role of A1 norepinephrine neurons.

We determined whether electrical stimulation of the abdominal vagus nerve causes secretion of vasopressin in the rabbit and whether inhibition of neuronal function in the A1 region of the medulla oblongata impairs this secretion. In urethan-anesthetized rabbits, electrical stimulation of the abdominal vagus (5-min train of cathodal pulses, 0.5 ms duration, 20 Hz, 0.5-1 mA) increased plasma vasopressin from 37 +/- 8 to 133 +/- 19 pg/ml (P < 0.01, n = 11). Prior section of the cervical vagus completely prevented the increase seen with stimulation of the abdominal vagus. Injecting the inhibitory agent muscimol (1 nmol) 2 mm dorsal to the A1 area did not significantly reduce the vasopressin response to abdominal vagal stimulation. However, when muscimol was injected into the A1 area, the vagally mediated increase in plasma vasopressin was completely prevented. Our results show that stimulation of abdominal vagal afferents causes secretion of vasopressin in the rabbit via a central pathway that includes neurons in the A1 area.

Abdomen↗