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Brain : a Journal of Neurology Jun 2018Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by...
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by post-ictal central respiratory depression, which could relate to underlying pathology in key respiratory nuclei and/or their neuromodulators. Our aim was to investigate neuronal populations in the ventrolateral medulla (which includes the putative human pre-Bötzinger complex) and the medullary raphe. Forty brainstems were studied comprising four groups: 14 SUDEP, six epilepsy controls, seven Dravet syndrome cases and 13 non-epilepsy controls. Serial sections through the medulla (from obex 1 to 10 mm) were stained for Nissl, somatostatin, neurokinin 1 receptor (for pre-Bötzinger complex neurons) and galanin, tryptophan hydroxylase and serotonin transporter (neuromodulatory systems). Using stereology total neuronal number and densities, with respect to obex level, were measured. Whole slide scanning image analysis was used to quantify immunolabelling indices as well as co-localization between markers. Significant findings included reduction in somatostatin neurons and neurokinin 1 receptor labelling in the ventrolateral medulla in sudden death in epilepsy compared to controls (P < 0.05). Galanin and tryptophan hydroxylase labelling was also reduced in sudden death cases and more significantly in the ventrolateral medulla region than the raphe (P < 0.005 and P < 0.05). With serotonin transporter, reduction in labelling in cases of sudden death in epilepsy was noted only in the raphe (P ≤ 0.01); however, co-localization with tryptophan hydroxylase was significantly reduced in the ventrolateral medulla. Epilepsy controls and cases with Dravet syndrome showed less significant alterations with differences from non-epilepsy controls noted only for somatostatin in the ventrolateral medulla (P < 0.05). Variations in labelling with respect to obex level were noted of potential relevance to the rostro-caudal organization of respiratory nuclear groups, including tryptophan hydroxylase, where the greatest statistical difference noted between all epilepsy cases and controls was at obex 9-10 mm (P = 0.034), the putative level of the pre-Bötzinger complex. Furthermore, there was evidence for variation with duration of epilepsy for somatostatin and neurokinin 1 receptor. Our findings suggest alteration to neuronal populations in the medulla in SUDEP with evidence for greater reduction in neuromodulatory neuropeptidergic and mono-aminergic systems, including for galanin, and serotonin. Other nuclei need to be investigated to evaluate if this is part of more widespread brainstem pathology. Our findings could be a result of previous seizures and may represent a pathological risk factor for SUDEP through impaired respiratory homeostasis during a seizure.
Topics: Adolescent; Adult; Autopsy; Death, Sudden; Epilepsy; Female; Humans; Magnetic Resonance Imaging; Male; Medulla Oblongata; Membrane Proteins; Middle Aged; Nerve Tissue Proteins; Raphe Nuclei; Retrospective Studies; Severity of Illness Index; Young Adult
PubMed: 29608654
DOI: 10.1093/brain/awy078 -
Pulmonary Pharmacology & Therapeutics Dec 2015The dorsal medulla encompassing the nucleus of the tractus solitarius (NTS) and surrounding reticular formation (RF) has an important role in processing sensory... (Review)
Review
The dorsal medulla encompassing the nucleus of the tractus solitarius (NTS) and surrounding reticular formation (RF) has an important role in processing sensory information from the upper and lower airways for the generation and control of airway protective behaviors. These behaviors, such as cough and swallow, historically have been studied in isolation. However, recent information indicates that these and other airway protective behaviors are coordinated to minimize risk of aspiration. The dorsal medullary neural circuits that include the NTS are responsible for rhythmogenesis for repetitive swallowing, but previous models have assigned a role for this portion of the network for coughing that is restricted to monosynaptic sensory processing. We propose a more complex NTS/RF circuit that controls expression of swallowing and coughing and the coordination of these behaviors. The proposed circuit is supported by recordings of activity patterns of selected neural elements in vivo and simulations of a computational model of the brainstem circuit for breathing, coughing, and swallowing. This circuit includes separate rhythmic sub-circuits for all three behaviors. The revised NTS/RF circuit can account for the mode of action of antitussive drugs on the cough motor pattern, as well as the unique coordination of cough and swallow by a meta-behavioral control system for airway protection.
Topics: Animals; Cough; Deglutition; Humans; Medulla Oblongata; Neural Pathways; Neurogenesis; Respiratory System
PubMed: 26549786
DOI: 10.1016/j.pupt.2015.10.012 -
The Journal of Physiology Mar 2015The rostral ventrolateral medulla oblongata (RVLM) contains two functionally distinct types of neurons that control and orchestrate cardiovascular and respiratory... (Review)
Review
The rostral ventrolateral medulla oblongata (RVLM) contains two functionally distinct types of neurons that control and orchestrate cardiovascular and respiratory responses to hypoxia and hypercapnia. One group is composed of the central chemoreceptor neurons of the retrotrapezoid nucleus, which provides a CO₂/H(+) -dependent drive to breathe and serves as an integration centre and a point of convergence of chemosensory information from other central and peripheral sites, including the carotid bodies. The second cluster of RVLM cells forms a population of neurons belonging to the C1 catecholaminergic group that controls sympathetic vasomotor tone in resting conditions and in conditions of hypoxia and hypercapnia. Recent evidence suggests that ATP-mediated purinergic signalling at the level of the RVLM co-ordinates cardiovascular and respiratory responses triggered by hypoxia and hypercapnia by activating retrotrapezoid nucleus and C1 neurons, respectively. The role of ATP-mediated signalling in the RVLM mechanisms of cardiovascular and respiratory activities is the main subject of this short review.
Topics: Animals; Carbon Dioxide; Chemoreceptor Cells; Humans; Medulla Oblongata; Receptors, Purinergic; Sympathetic Nervous System
PubMed: 25524282
DOI: 10.1113/jphysiol.2014.284430 -
Physiology & Behavior Sep 2019Glucose is the required metabolic substrate for the brain. Yet the brain stores very little glucose. Therefore, the brain continuously monitors glucose availability to... (Review)
Review
Glucose is the required metabolic substrate for the brain. Yet the brain stores very little glucose. Therefore, the brain continuously monitors glucose availability to detect hypoglycemia and to mobilize system-wide responses to protect and restore euglycemia. Catecholamine (CA) neurons in the hindbrain are critical elements of the brain's glucoregulatory mechanisms. They project widely throughout the brain and spinal cord, innervating sites controlling behavioral, endocrine and visceral responses. Hence, CA neurons are capable of triggering a rapid, coordinated and multifaceted response to glucose challenge. This article reviews experimental data that has begun to elucidate the importance of CA neurons for glucoregulation, the functions of specific CA subpopulations in the ventrolateral medulla, and the extended circuitry through which they engage other levels of the nervous system to accomplish their essential glucoregulatory task. Hopefully, this review also suggests the vast amount of work yet to be done in this area and the justification for engaging in that effort.
Topics: Animals; Glucose; Medulla Oblongata; Neurons; Rhombencephalon
PubMed: 31173784
DOI: 10.1016/j.physbeh.2019.112568 -
Neurology India 2009
Topics: Aged; Cerebellum; Female; Humans; Intracranial Aneurysm; Magnetic Resonance Imaging; Male; Medulla Oblongata; Middle Aged; Siderosis; Tomography, X-Ray Computed
PubMed: 19934584
DOI: 10.4103/0028-3886.57785 -
ELife Oct 2022Regulation of systemic PCO is a life-preserving homeostatic mechanism. In the medulla oblongata, the retrotrapezoid nucleus (RTN) and rostral medullary Raphe are...
Regulation of systemic PCO is a life-preserving homeostatic mechanism. In the medulla oblongata, the retrotrapezoid nucleus (RTN) and rostral medullary Raphe are proposed as CO chemosensory nuclei mediating adaptive respiratory changes. Hypercapnia also induces active expiration, an adaptive change thought to be controlled by the lateral parafacial region (pF). Here, we use GCaMP6 expression and head-mounted mini-microscopes to image Ca activity in these nuclei in awake adult mice during hypercapnia. Activity in the pF supports its role as a homogenous neuronal population that drives active expiration. Our data show that chemosensory responses in the RTN and Raphe differ in their temporal characteristics and sensitivity to CO, raising the possibility these nuclei act in a coordinated way to generate adaptive ventilatory responses to hypercapnia. Our analysis revises the understanding of chemosensory control in awake adult mouse and paves the way to understanding how breathing is coordinated with complex non-ventilatory behaviours.
Topics: Mice; Animals; Hypercapnia; Carbon Dioxide; Medulla Oblongata; Brain Stem; Respiration
PubMed: 36300918
DOI: 10.7554/eLife.70671 -
Brazilian Journal of Medical and... Jul 2008It is well known that the ventrolateral medulla contains neurons involved in the tonic and reflex control of the cardiovascular system. Two regions within the... (Review)
Review
It is well known that the ventrolateral medulla contains neurons involved in the tonic and reflex control of the cardiovascular system. Two regions within the ventrolateral medulla were initially identified: the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Activation of the RVLM raises arterial blood pressure and sympathetic nerve activity, and activation of the CVLM causes opposite effects. The RVLM premotor neurons project directly to sympathetic preganglionic neurons and are involved in the maintenance of resting sympathetic vasomotor tone. A significant proportion of tonic activity in the RVLM sympathetic premotor neurons is driven by neurons located in a third region of the ventrolateral medulla denominated caudal pressor area (CPA). The CPA is a pressor region located at the extreme caudal part of the ventrolateral medulla that appears to have an important role controlling the activity of RVLM neurons. In this brief review, we will address the importance of the ventrolateral medulla neurons for the generation of resting sympathetic tone related to arterial blood pressure control focusing on two regions, the RVLM and the CPA.
Topics: Animals; Blood Pressure; GABA Agents; Medulla Oblongata; Microinjections; Neural Inhibition; Neurons; Sympathetic Nervous System; Vasomotor System; gamma-Aminobutyric Acid
PubMed: 18719736
DOI: 10.1590/s0100-879x2008000700002 -
Neurologia Medico-chirurgica Nov 2001The occurrence of neurogenic pulmonary edema (NPE) associated with subarachnoid hemorrhage (SAH) due to ruptured aneurysm was analyzed in 48 consecutive patients.... (Review)
Review
The occurrence of neurogenic pulmonary edema (NPE) associated with subarachnoid hemorrhage (SAH) due to ruptured aneurysm was analyzed in 48 consecutive patients. Correlations of the location of the aneurysm, clinical grade, amount of subarachnoid clot, and severity of NPE were examined. NPE was observed in 29.4% of all SAH cases, but the incidence was significantly higher in cases of ruptured vertebral artery (VA) aneurysm. Clinical grade, severity of NPE, and deformation of the medulla oblongata were studied in the five cases of ruptured VA aneurysm. Deformation of the ventrolateral medulla oblongata was observed in all patients. Asymmetry index of the medulla oblongata measured on the axial computed tomography scan was correlated with the severity of NPE. Severity of NPE tended to correlate with deformation of the medulla oblongata. NPE associated with ruptured VA aneurysm is caused by deformation of the ventrolateral site of the medulla oblongata by the localized hemorrhage.
Topics: Adult; Aged; Aged, 80 and over; Aneurysm, Ruptured; Blood Glucose; Catecholamines; Female; Humans; Hypothalamus; Incidence; Intracranial Aneurysm; Male; Medulla Oblongata; Middle Aged; Pulmonary Edema; Rupture, Spontaneous; Subarachnoid Hemorrhage
PubMed: 11758704
DOI: 10.2176/nmc.41.529 -
BMC Neurology May 2021The course of the corticobulbar tract (CBT) to the facial nucleus has been investigated by some previous studies. However, there are some unclear points of the course of...
BACKGROUND
The course of the corticobulbar tract (CBT) to the facial nucleus has been investigated by some previous studies. However, there are some unclear points of the course of the CBT to the facial nucleus. This study aimed to elucidate the detailed course of the CBT to the facial nucleus through the analysis of lateral medullary infarction (LMI) cases.
METHODS
The neurological characteristics and magnetic resonance imaging findings of 33 consecutive patients with LMI were evaluated. The location of the lesions was classified rostro-caudally (upper, middle, or lower) and horizontally. Further, we compared the neurological characteristics between the groups with and without central facial paresis (FP).
RESULTS
Eight (24%) patients with central FP ipsilateral to the lesion were identified. Dysphagia and hiccups were more frequently observed in the group with central FP than in the group without central FP. In patients with central FP, middle medullary lesions and those including the ventral part of the dorsolateral medulla were more frequently observed. Contrastingly, patients with lesions restricted to the lateral and dorsal regions of the dorsolateral medulla did not present with central FP.
CONCLUSION
The results of this study indicate that the CBT to the facial nucleus descends with the corticospinal tract at least to the middle portion of the medulla, and then ascends to the facial nucleus through the medial and ventral areas of the dorsolateral medulla after decussation.
Topics: Facial Paralysis; Humans; Magnetic Resonance Imaging; Medulla Oblongata; Pyramidal Tracts
PubMed: 34058995
DOI: 10.1186/s12883-021-02247-z -
Respiratory Physiology & Neurobiology Jun 2010Recent studies in vivo and in vitro suggest that both respiratory rhythmogenesis and its central chemosensory modulation arise from multiple, mechanistically and/or... (Review)
Review
Recent studies in vivo and in vitro suggest that both respiratory rhythmogenesis and its central chemosensory modulation arise from multiple, mechanistically and/or anatomically distinct networks whose outputs are similar. These observations are consistent with degeneracy, defined as the ability of structurally distinct elements to generate similar function. This review argues that degeneracy is an essential feature of respiratory networks, ensuring the survival of the individual organism over the course of development, and accounting for the transformation of respiratory biomechanics over evolutionary time. At faster timescales, respiration must adapt continuously and rapidly to changes in metabolic demand and ambient conditions to maintain blood-gas homeostasis. Control theory, which formalizes homeostasis, states axiomatically that rapid responsiveness can only be achieved with high gain, but high gain comes at the cost of instability. Homeostatic systems displaying highly optimized tolerance (HOT) mitigate the instability accompanying high gain by incorporating regulatory mechanisms that provide protection against expected perturbations, yet these systems remain fragile to catastrophic failure in response to rare events. Because the multiple mechanisms that are conjectured to mediate respiratory rhythmogenesis and chemosensation have distinct ranges of activity and responses to modulatory input, they provide a richer substrate for respiratory regulation than those of any single mechanism. Respiration, though robust, remains fragile to rare perturbations, matching a key feature of HOT. These observations support the conclusion that degeneracy provides the substrate for respiratory regulation, and that the resulting regulatory system conforms to HOT.
Topics: Animals; Biological Evolution; Chemoreceptor Cells; Homeostasis; Humans; Medulla Oblongata; Models, Biological; Nerve Net; Periodicity; Respiration
PubMed: 20412870
DOI: 10.1016/j.resp.2010.04.013