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W W Blessing

Publications and source records attributed to W W Blessing.

At least 91 records · Page 5Linked to original sources

Localization of vasodepressor neurons in the caudal ventrolateral medulla in the rabbit.

The precise distribution of vasodepressor neurons in the caudal ventrolateral medulla has been mapped in the rabbit using very small injections of L-glutamate (0.5 nmol in 25 nl or 0.1 nmol of 10 nl of Ringer solution). The vasodepressor neurons are discretely located in a circumscribed region of the lateral reticular formation, ventral and ventrolateral to the nucleus ambiguus, from 0.5 mm to 2.5 mm caudal to the obex. The results indicate that the vasodepressor neurons in the caudal ventrolateral medulla are confined to a relatively limited region, not corresponding to any defined nucleus.

Animals↗

Loss of brainstem serotonin- and substance P-containing neurons in Parkinson's disease.

Using postmortem immunohistochemical analysis, we have identified degeneration of several different neuronal cell groups in the brainstem of patients dying with idiopathic Parkinson's disease. We report the first chemically identified loss of presumed serotonin neurons in the median raphe nucleus of the pons and of substance P-containing preganglionic neurons in the dorsal motor vagal nucleus. This evidence is concordant with other evidence that the primary neuropathological process is not confined either to a single pathway or to neurons containing a particular transmitter. Rather it appears that Parkinson's disease affects several classes of neurons in localized areas of the brainstem.

Antibodies, Monoclonal↗

Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease.

Regional loss of immunohistochemically identified neurons in serial sections through the brainstem of 4 patients with idiopathic Parkinson's disease was compared with equivalent sections from 4 age-matched control subjects. In the Parkinson brains, the catecholamine cell groups of the midbrain, pons, and medulla showed variable neuropathological changes. All dopaminergic nuclei were variably affected, but were most severely affected in the caudal, central substantia nigra. The pontine noradrenergic locus ceruleus showed variable degrees of degeneration. There was also a substantial loss of substance P-containing neurons in the pedunculopontine tegmental nucleus. However, the most severely affected cell group in the pons was the serotonin-synthesizing neurons in the median raphe. In the medulla, substantial neuronal loss was found in several diverse cell groups including the adrenaline-synthesizing and neuropeptide Y-containing neurons in the rostral ventrolateral medulla, the serotonin-synthesizing neurons in the raphe obscurus nucleus, the substance P-containing neurons in the lateral reticular formation, as well as the substance P-containing neurons in the dorsal motor vagal nucleus. Lewy bodies were present in immunohistochemically identified neurons in many of these regions, indicating that they were affected directly by the disease process. These widespread but region- and transmitter-specific changes help account for the diversity of motor, cognitive, and autonomic manifestations of Parkinson's disease.

Aged↗

Distribution of glutamate decarboxylase-containing neurons in rabbit medulla oblongata with attention to intramedullary and spinal projections.

Functional studies in the rabbit suggest that GABA is an important inhibitory neurotransmitter in the control of cardiovascular, respiratory and neuroendocrine functions by the medulla oblongata. The present work was undertaken to provide a description of the distribution in the rabbit medulla of neurons containing glutamate decarboxylase, an enzyme present in GABA-synthesizing neurons. Combined retrograde axonal transport and immunohistochemical studies were carried out to determine intramedullary and spinal projections of immunopositive neurons located in regions particularly relevant to the interpretation of functional studies. Neurons containing glutamate decarboxylase, putatively GABA-containing neurons, were found in all nuclei of the rabbit medulla with the exception of somatic cranial nerve nuclei and the lateral reticular nucleus. The immunopositive cells were distributed throughout individual nuclei and their morphological appearance was similar to that of neighbouring immunonegative neurons in the nucleus. An exception was encountered in the dorsal motor nucleus of the vagus where the glutamate decarboxylase-containing neurons belong to a population of small neurons easily distinguished from the larger vagal preganglionic cells. Many immunopositive cells in the raphe nuclei, in the medial reticular formation and in the vestibular nuclei have axonal projections to the spinal cord and presumably represent sources of inhibitory bulbospinal control. Within the medulla there were glutamate decarboxylase-containing neurons in the nucleus tractus solitarius with projections to caudal but not to rostral regions of the ventrolateral medulla. These neurons could provide a GABAergic input to respiratory, cardiovascular and neuroendocrine neurons in the caudal ventrolateral medulla. Immunopositive cells projecting from the caudal to the rostral ventrolateral medulla could form part of the population of inhibitory vasomotor neurons known to be present in the caudal ventrolateral medulla. Some glutamate decarboxylase-containing neurons just medial to the nucleus ambiguous in the rostral medulla, in the region containing the Botzinger group, project to the caudal ventrolateral medulla and could therefore provide an inhibitory input to caudal respiratory cells.

Animals↗

Substance P-containing neurons in the pontomesencephalic tegmentum of the human brain.

We have employed immunohistochemical and computerized morphometric procedures to study substance P-containing neurons in the tegmentum of adult humans. An estimated 192,500 +/- 40,500 substance P-containing neurons were found in three main cytoarchitectural regions: the mesencephalic reticular formation, the central gray, and the pontine reticular formation. The morphology of the immunoreactive neurons varied according to the region in which they were found. On the basis of size alone two types of substance P-containing neurons, large and small, were readily distinguishable by eye and measurement. Within each of the three main regions it was possible to distinguish distinct subgroups using cell size, morphology and position. Large neurons were concentrated in the caudal midbrain (pedunculopontine tegmental nuclei), in the oral pontine reticular nucleus and in the lateral dorsal tegmental nucleus. In contrast, small neurons were concentrated in the rostral mesencephalic reticular formation (cuniform nuclei). Both small and large neurons were found in the midbrain and pontine raphe nuclei. In addition, small neurons were concentrated in discrete midline regions (the periaqueductal gray, the tegmental nuclei of the pontine central gray, and the interpeduncular nucleus). The findings suggest that the majority of neurons in the brainstem tegmental nuclei previously identified as cholinergic also contain substance P in humans.

Aged↗

PNMT-containing neurons in the rostral medulla oblongata (C1, C3 groups) are transneuronally labelled after injection of herpes simplex virus type 1 into the adrenal gland.

Herpes simplex virus type 1 (HSV1) was injected into the rat adrenal gland. After 3 days the rat CNS was processed immunohistochemically to demonstrate viral antigen. In the lower thoracic spinal cord viral antigen was found in neurons in the intermediolateral column. In the medulla oblongata HSV1-positive neurons were found in the raphe pallidus and in the C1 and C3 regions of the rostral medulla. Approximately 50% of HSV1-positive neurons in the C1 and all the HSV1-positive neurons in the C3 area also contained phenylethanolamine N-methyltransferase (PNMT) and were thus identified as C1 and C3 cells. The HSV1-positive neurons in the C1 region which did not contain PNMT were also negative for tyrosine hydroxylase and were therefore not catecholamine-synthesizing neurons. The HSV1-positive neurons in the medulla oblongata were presumably transsynaptically labelled from the adrenal gland and our study therefore provides neuroanatomical evidence supporting the view that some C1 neurons are involved in controlling the function of the adrenal gland.

Adrenal Glands↗

Baroreceptor-vasomotor reflex after N-methyl-D-aspartate receptor blockade in rabbit caudal ventrolateral medulla.

1. Experiments were performed in anaesthetized rabbits to determine whether blockade of N-methyl-D-aspartate receptors in the caudal ventrolateral medulla oblongata prevents the changes in renal sympathetic vasomotor activity which normally occur in response to increases or decreases in arterial pressure. 2. N-Methyl-D-aspartic acid receptor blockade using bilateral injections of either kynurenic acid (5 nmol) or DL-amino-5-phosphonovaleric acid (5 nmol) caused a rise in arterial pressure with a variable change in renal sympathetic nerve activity. 3. The depressor and renal sympathoinhibitory responses normally seen after intramedullary injection of N-methyl-D-aspartic acid (50 pmol) into the caudal ventrolateral medulla were entirely prevented by prior receptor blockade. The corresponding responses to L-glutamate (10 nmol) were not affected. 4. The depressor and renal sympathoinhibitory responses normally seen with electrical stimulation of the aortic depressor nerve were abolished by the receptor blockade. 5. The reflex inhibition of renal sympathetic nerve activity normally seen in response to increasing arterial pressure using a cuff around the descending aorta was not affected by kynurenic acid. The response was reduced by DL-amino-5-phosphonovaleric acid but a significant degree of inhibition was preserved. The reflex increase in renal sympathetic nerve activity normally seen in response to reducing arterial pressure using a cuff occluder around the inferior vena cava was unchanged after injection of DL-amino-5-phosphonovaleric acid and was increased in magnitude after injection of kynurenic acid. 6. The results indicate that blockade of excitatory amino acid receptors in the caudal ventrolateral medulla of the rabbit abolishes the depressor response evoked by electrical stimulation of the aortic nerve but leaves intact the normal baroreceptor-vasomotor responses elicited by raising or lowering arterial pressure.

2-Amino-5-phosphonovalerate↗

Neuropeptide Y-like immunoreactivity is present in boutons synapsing on vasopressin-containing neurons in rabbit supraoptic nucleus.

Ultrastructural immunocytochemical methods were used to examine the relationship between nerve terminals containing neuropeptide Y-like immunoreactivity and vasopressin-containing neurons in the rabbit supraoptic nucleus. Some boutons containing neuropeptide Y-like immunoreactivity formed synapses on the soma and proximal dendrites of vasopressin-containing neurons.

Animals↗

Tyrosine hydroxylase-containing neurons in the supraoptic and paraventricular nuclei of the adult human.

We have studied the distribution of tyrosine hydroxylase-containing neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the adult human hypothalamus. Large numbers of these neurons were seen in these hypothalamic nuclei; approximately 40% of all the cells within the SON and PVN were immunoreactive for tyrosine hydroxylase (TH-ir). Most of these cells were magnocellular. Their distribution was compared to that of arginine-vasopressin-immunoreactive (AVP-ir) cells. In the SON a greater proportion of magnocellular TH-ir cells was found caudally compared to AVP-ir cells. In the PVN the magnocellular TH-ir cells were larger in mean diameter compared to AVP-ir cells. In double-immunofluorescence experiments some TH-ir cells contained oxytocin immunoreactivity but none contained AVP-ir. In the adult human a large number of PVN and SON magnocellular cells appear to synthesize a catecholamine. A subclass of these neurons also synthesize oxytocin but most cells are distinct from the classically described neurosecretory neurons.

Aged↗

Distribution of monoamine-synthesizing neurons in the human medulla oblongata.

We have employed immunohistochemical and morphometric procedures to study the distribution of monoamine-synthesizing neurons in the medulla oblongata of the adult human, utilizing antibodies to tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and phenylalanine hydroxylase (PH8). In the human brain, the antigen with which PH8 reacts occurs within neurons that presumably synthesize serotonin (Haan et al., '87). Neurons containing these antigens were mapped and counted in successive coronal sections with the aid of a computer-assisted procedure. The results indicate that monoamine-synthesizing neurons are distributed in the human brain in patterns broadly similar to those described for other species. TH-immunoreactive cells extended caudorostrally for approximately 32 mm commencing at the spinomedullary junction and ending 8 mm caudal to the pontomedullary junction. In coronal sections these TH-immunoreactive neurons were seen in the lateral medulla dorsal to the inferior olive extending in a continuous band to the dorsomedial medulla. Above the obex the majority of these cells apparently synthesize adrenaline since many PNMT-immunoreactive cells were also found in this region. There were few or no PNMT-immunoreactive cells caudal to the obex, indicating that the TH-immunoreactive cells in this region synthesize either noradrenaline or dopamine. Approximately 65% of these TH-immunoreactive neurons contained melanin pigment, whereas few or no PNMT-immunoreactive cells contained melanin pigment. PH8-immunoreactive cells extended throughout the rostrocaudal extent of the medulla oblongata (approximately 40 mm). In coronal sections the majority were found in the medullary raphe nuclei. However, many cells throughout the rostrocaudal extent of the medulla were found laterally intermingled with catecholamine-synthesizing neurons. Occasional neurons in the lateral medulla appeared to contain both PH8- and TH-immunoreactivity.

Aged↗

Distribution of substance P-like immunoreactive neurons in the human medulla oblongata: co-localization with monoamine-synthesizing neurons.

The raphe nuclei also contained SP-like immunoreactivity (up to 30%) while few monoamine-synthesizing neurons in the lateral and dorsomedial medulla contained SP-like immunoreactivity (approximately 5% of presumed serotonin-, noradrenaline-, and adren- the adult human. The majority of SP-like immunoreactive neurons were found in four main regions: the lateral medulla, the dorsomedial medulla, the spinal trigeminal nucleus, and the raphe nuclei. The morphology of immunoreactive cells varied according to the region in which they were found. In contrast to previous studies, we found large numbers (90,000) of SP-like immunoreactive neurons throughout the adult human medulla oblongata. The distribution of these SP-like immunoreactive neurons appears to be significantly different from those described in the rat and cat. These results were compared to the distributions of monoamine-synthesizing and neuropeptide Y (NPY)-like immunoreactive neurons in the human medulla previously reported (Halliday et al.: Neuroscience, in press, 1988a; J. Comp. Neurol., in press, 1988b). Colocalization studies revealed that many presumed serotonin-synthesizing neurons in the raphe nuclei also contained SP-like immunoreactivity (up to 30%) while few monoamine-synthesizing neurons in the lateral and dorsomedial medulla contained SP-like immunoreactivity (approximately 5% of presumed serotonin-, noradrenaline-, and adrenaline-synthesizing neurons). The distributions of SP- and NPY-like immunoreactive neurons were similar, although SP-like immunoreactive neurons were concentrated in the lateral regions of the same structures. We have found that the distributions of monoamine-synthesizing, NPY-, and SP-like immunoreactive neurons significantly overlap, particularly in the lateral medulla of the adult human. There is a large increase in the number of these cells in this region compared to other species, emphasizing the neuroanatomical differences between humans and other species.

Aged↗

Origin of tonic GABAergic inputs to vasopressor neurons in the subretrofacial nucleus of the rabbit.

The aims of this study were to determine (1) whether the vasomotor effects reflexly elicited by baroreceptor stimulation are dependent upon gamma-aminobutyric acid (GABA) receptors in the subretrofacial (SRF) nucleus in the rostral ventrolateral medulla; (2) the extent to which inputs other than those arising from peripheral baroreceptors, or transmitted via the nucleus tractus solitarius (NTS), contribute to the tonic GABAergic inhibition of SRF vasopressor cells. Following bilateral injection of a mixture of the GABA antagonist bicuculline methiodide (500 pmol) and GABA agonist muscimol (500 pmol) into the SRF nucleus, the sympathoinhibitory response normally evoked by a rise in arterial pressure (induced by inflating an aortic cuff) was abolished in 4 out of 8 rabbits and reduced in the remainder. For the whole group, the mean reduction in this response was 71%. In other experiments, the pressor response produced by injection of bicuculline methiodide into the SRF nucleus was still present after (1) destruction of the intermediate portion of the NTS, and (2) complete removal of the brain rostral to the pons. We conclude that (1) an inhibitory GABAergic input into the SRF nucleus is an important component of the central pathways mediating baroreceptor inhibition of sympathetic vasomotor tone; (2) the SRF nucleus also receives tonic GABAergic inputs that are intrinsic to the lower brainstem and are independent of baroreceptor or other cardiovascular inputs relayed by the NTS.

Animals↗

The distribution of neuropeptide Y-like immunoreactive neurons in the human medulla oblongata.

We have described the distribution of neuropeptide Y-like immunoreactive neurons in the medulla oblongata of the adult human. The majority of neuropeptide Y-like immunoreactive cells were found in four regions of the medulla: the ventrolateral reticular formation, the dorsomedial medulla, the secondary sensory nuclei and the rostral raphe nuclei. The morphology of neuropeptide Y-like immunoreactive cells varied in each of these regions. In the ventrolateral reticular formation, the labelled neurons were round and pigmented caudal to the obex but elongated and non-pigmented rostral to the obex; in the dorsomedial medulla, they were triangular and pigmented caudal to but not rostral to the obex; in the secondary sensory nuclei, they were multipolar, non-pigmented and significantly smaller than in the other areas; in the rostral raphe nuclei, they were bipolar and non-pigmented. Colocalization studies revealed that many neuropeptide Y-like immunoreactive cells also synthesize monoamines, consistent with conclusions based on a quantitative comparison of their distributions. Neuropeptide Y-like immunoreactivity was present in about 25% of presumed noradrenaline-synthesizing cells in the caudal ventrolateral medulla (corresponding to the A1 region); about 50% of adrenaline- and 70% of presumed serotonin-synthesizing cells in the rostral ventrolateral medulla (C1 and B2-3 regions); 90-100% of presumed noradrenaline-synthesizing cells in the dorsomedial medulla at and above the obex (A2 region); about 50% of adrenaline-synthesizing cells in the rostral dorsomedial medulla (C2 region); about 5% of presumed serotonin-synthesizing cells in the rostral raphe nuclei (B2-3 region). The largest of these groups was the presumed serotonin-synthesizing cells that contained neuropeptide Y-like immunoreactivity in the rostral ventrolateral medulla. This is the first report of such a cell group in the medulla of any mammal, and emphasizes the neuroanatomical differences between humans and other species.

Aged↗

Depressor neurons in rabbit caudal medulla act via GABA receptors in rostral medulla.

Experiments were conducted in urethan-anesthetized rabbits to determine whether vasomotor effects elicited by activation or inhibition of the caudal ventrolateral medulla depend on gamma-aminobutyric acid (GABA)ergic, glycinergic, or alpha-adrenergic receptors in the region of the rostral ventrolateral medulla, which contains the bulbospinal sympathoexcitatory neurons. Bilateral injection of bicuculline methiodide into the rostral medulla caused a dose-related reduction in the fall in arterial pressure and in the inhibition of renal sympathetic nerve activity normally elicited by chemical stimulation of neurons in the caudal medulla using local injection of L-glutamate. When both bicuculline and muscimol were injected into the rostral medulla at the same time, resting arterial pressure was maintained at base-line levels, and the sympathoexcitatory neurons remained normally excitable by local injection of L-glutamate into the rostral medulla. In the presence of this mixed antagonist-agonist GABAergic blockade, both decreases and increases in arterial pressure elicited by excitation or inhibition of neuronal function in the caudal medulla were abolished. Similar effects were not observed after blockade of glycinergic or alpha-adrenergic receptors in the rostral ventrolateral medulla. Results suggest that the depressor neurons in the caudal ventrolateral medulla alter peripheral sympathetic vasomotor activity almost entirely by an action on GABAergic receptors in the rostral ventrolateral medulla.

Animals↗

Vestibulospinal pathway in rabbit includes GABA-synthesizing neurons.

When Fast blue is injected into the rabbit spinal cord it is retrogradely transported into nerve cell bodies located in the medial and the descending vestibular nuclei. Approximately 50% of the Fast blue-positive cells also contain glutamic acid decarboxylase-like immunoreactivity. These neurons presumably synthesize gamma-aminobutyric acid (GABA) and the rabbit vestibulospinal pathway therefore contains a substantial inhibitory component.

Amidines↗

Inhibition of vasodepressor neurons in the caudal ventrolateral medulla of the rabbit increases both arterial pressure and the release of neuropeptide Y-like immunoreactivity from the spinal cord.

The role of bulbospinal neuropeptide Y (NPY)-containing neurons of the rostral ventrolateral medulla in the rabbit in mediating the increase in blood pressure that occurs during inhibition of cells in the caudal ventrolateral medulla was investigated in urethane-anaesthetized rabbits. In the present experiments bilateral injections of the GABA agonist, muscimol, into the caudal ventrolateral medulla elicited a slowly-developing rise in arterial pressure that was maximal 15 min after the injection. Accompanying this increase in arterial pressure was an increase in the release of NPY-like immunoreactivity (NPY-LI) into the spinal subarachnoid space. This pattern of response is similar to that seen after direct chemical stimulation of the NPY-containing cells of the rostral ventrolateral medulla. Taken together, these findings suggest that tonically active neurons in the caudal ventrolateral medulla exert their effects by inhibiting sympathoexcitatory NPY-containing neurons whose cell bodies are situated in the rostral ventrolateral medulla.

Animals↗

Neurons in the area postrema are the only catecholamine-synthesizing cells in the medulla or pons with projections to the rostral ventrolateral medulla (C1-area) in the rabbit.

We have identified, in the rabbit medulla and pons, neurons which project to the C1-region of the rostral ventrolateral medulla. By combining tyrosine hydroxylase immunohistochemistry with retrograde transport of Fluoro-Gold we determined whether any of the retrogradely labelled neurons synthesize catecholamines. The only doubly labelled cells were located in the area postrema. No other group of catecholamine-synthesizing neurons in either the medulla or the pons was found to project to the C1-area of the rostral ventrolateral medulla. Pharmacological agents which lower arterial pressure by stimulating adrenoceptors in the rostral ventrolateral medulla may act on receptors which are not innervated by catecholamine-synthesizing perikarya located outside the C1-region.

Animals↗