Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence and distribution of a cerebrovascular cholinergic system were studied in goats. Regional cerebral blood flow was measured in the parietal cerebral cortex, caudate nucleus, and white matter by the hydrogen clearance technique in unanesthetized goats. Intravenous low doses of physostigmine, but not of neostigmine, significantly increased regional blood flow without changing mean arterial blood pressure or behavior. Increases of blood flow were greater in cerebral cortex and caudate nucleus than in white matter although the vasodilation induced by hypercapnia was similar in the three regions. Intracerebral microvessels were isolated from cerebral cortex, caudate nucleus, and white matter to evaluate choline acetyltransferase activity as a marker for perivascular cholinergic nerves. The enzyme level was higher in vessels from cerebral cortex and caudate nucleus than in vessels from white matter, which is in accordance with the functional data. These results suggest the presence of a cholinergic perivascular innervation system in intracerebral microvessels. Such innervation has a nonhomogeneous distribution throughout the brain and might be implicated in the local regulation of cerebral blood flow.
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PMID:Regional differences in cerebrovascular cholinergic innervation in goats. 337 65

The human arcuate nucleus (ArcN) has been considered akin to the pontine precerebellar nuclei. However, there is anatomical, functional, and clinical evidence that the ArcN may be the homologue of chemosensitive areas of the ventral medullary surface involved in ventilatory responses to hypercarbia and cerebrospinal fluid acidosis. Acetylcholine has been involved in mechanisms of central chemosensitivity. Loss of ArcN neurons has been reported in patients with multiple system atrophy (MSA), a disorder characterized by disturbed automatic ventilation, but the neurochemical identity of these neurons is undetermined. We sought to determine whether the ArcN contains cholinergic neurons and whether these neurons are depleted in patients with MSA. Medullae were obtained from six patients with MSA, five patients with Parkinson's disease (PD) and six sex- and age-matched controls. Fifty-micron transverse sections obtained through the mid-olivary levels were processed for acetylcholinesterase (AchE), choline acetyltransferase (CAT), and alpha-synuclein immunoreactivity. We found that the ArcN contained CAT-positive neurons. There was a significant decrease in density of cholinergic ArcN neurons in MSA but not in PD patients. alpha-Synuclein-containing inclusions were present in the ArcN of MSA patients. Depletion of cholinergic neurons may provide a substrate for disturbances in automatic respiration in MSA patients.
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PMID:Depletion of cholinergic neurons of the medullary arcuate nucleus in multiple system atrophy. 1147 92

Pelizaeus Merzbacher disease is an X-linked dysmyelinating disorder of the CNS, resulting from mutations in the proteolipid protein (PLP) gene. An animal model for this disorder, the myelin-deficient (MD) rat, carries a point mutation in the PLP gene and exhibits a phenotype similar to the fatal, connatal disease, including extensive dysmyelination, tremors, ataxia, and death at approximately postnatal day 21 (P21). We postulated that early death might result from disruption of myelinated neural pathways in the caudal brainstem and altered ventilatory response to oxygen deprivation or hypercapnic stimulus. Using barometric plethysmography to measure respiratory function, we found that the MD rat develops lethal hypoxic depression of breathing at P21, but hypercapnic ventilatory response is normal. Histologic examination of the caudal brainstem in the MD rat at this age showed extensive dysmyelination and downregulation of NMDA and to a lesser extent GABA(A) receptors on neurons in the nucleus tractus solitarius, hypoglossal nucleus, and dorsal motor nucleus of the vagus. Unexpectedly, immunoreactive PLP/DM20 was detected in neurons in the caudal brainstem. Not all biosynthetic functions and structural elements were altered in these neurons, because phosphorylated and nonphosphorylated neurofilament and choline acetyltransferase expression were comparable between MD and wild-type rats. These findings suggest that PLP is expressed in neurons in the developing brainstem and that PLP gene mutation can selectively disrupt central processing of afferent neural input from peripheral chemoreceptors, leaving the central chemosensory system for hypercapnia intact.
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PMID:Proteolipid protein gene mutation induces altered ventilatory response to hypoxia in the myelin-deficient rat. 1265 85

This study tested the hypothesis that during hypercapnia or hypoxia, airway-related vagal preganglionic neurons (AVPNs) of the nucleus ambiguus (NA) release acetylcholine (ACh), which in a paracrine fashion, activates ACh receptors expressed by inspiratory rhythm generating cells. AVPNs in the NA were ablated by injecting a saporin- (SA) cholera toxin b subunit (CTb-SA) conjugate into the extra-thoracic trachea (n=6). Control animals were injected with free CTb (n=6). In CTb treated rats, baseline ventilation and ventilatory responses to hypercapnia (5 and 12% CO(2) in O(2)) or hypoxia (8% O(2) in N(2)) were similar (p>0.05) prior to and 5 days after injection. CTb-SA injected rats maintained rhythmic breathing patterns 5 days post injection, however, tachypneic responses to hypercapnia or hypoxia were significantly reduced. The number of choline acetyltransferase (ChAT) immunoreactive cells in the NA was much lower (p<0.05) in CTb-SA rats as compared to animals receiving CTb only. These results suggest that AVPNs participate in the respiratory frequency response to hypercapnia or hypoxia.
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PMID:Ablation of vagal preganglionic neurons innervating the extra-thoracic trachea affects ventilatory responses to hypercapnia and hypoxia. 1609 24