Ventrolateral Medulla Oblongata Research Articles

Laterality of Skin Temperature and Magnetic Resonance Imaging in Patients with Wallenberg Syndrome

Background: Recently, lateral differences in body surface temperature (BST) have been reported as a symptom of Wallenberg syndrome (WS), resulting from disturbances in the sympathetic nerve pathway. This study aimed to investigate the relationship between the laterality of BST and brain magnetic resonance imaging (MRI) findings in 12 patients with WS.Methods: BST was measured using an infrared thermal camera at 7±3 days and 90±30 days after symptom onset. The MRI findings were categorized as rostral, middle, and caudal medulla rostrocaudally and typical, ventral, large, dorsal, and lateral types in the horizontal direction.Results: MRI revealed medullary lesions on the right in five patients and on the left in seven patients. Two patients without lateralized BST had lateral caudal medullary infarction, and one patient had a dorsal middle medullary infarction. One patient with lateralized BST had a rostral medullary infarction and the other had a typical or large middle medulla infarction. Lateralized BST in patients with WS may disturb the sympathetic nervous system pathway that descends from the rostral ventrolateral medulla oblongata. Deficits in sweating and skin blood flow may cause BST laterality.Conclusion: This study showed that lateralized BST in patients with WS may be associated with disturbances in the sympathetic nervous pathway descending from the rostral ventrolateral medulla. These results support the assumption that autonomic dysfunction may be related to abnormal sensory symptoms in patients with WS.

Transmastoid Trautman's Triangle Combined Low Retrosigmoid Approach for Foramen Magnum Meningiomas: Surgical Anatomy and Technical Note.

Objective This study was aimed to assess the potential of utilizing a transmastoid Trautman's triangle combined low retrosigmoid approach for ventral and ventrolateral foramen magnum meningiomas (FMMs) surgical treatment. Methods We simulated this transmastoid Trautman's triangle combined low retrosigmoid approach using five adult cadaveric heads to explore the associated anatomy in a step-by-step fashion, taking pictures of key positions as appropriate. We then employed this approach in a single overweight patient with a short neck who was suffering from large ventral FMMs and cerebellar tonsillar herniation. Results Through cadaver studies, we were able to confirm that this transmastoid Trautman's triangle combined with low retrosigmoid approach achieves satisfactory cranial nerve and vasculature visualization while also offering a wide view of the whole of the ventrolateral medulla oblongata. We, additionally, have successfully employed this approach to treat a single patient suffering from large ventral FMMs with cerebellar tonsillar herniation. Conclusion This transmastoid Trautman's triangle combined low retrosigmoid approach may represent a complement to treatment strategies for ventral and ventrolateral FMMs, particularly in patients with the potential for limited surgical positioning due to their being overweight, having a short neck and suffering from cerebellar tonsillar herniation.

The Role Of Parafacial Neurons In The Control Of Breathing During Exercise

Neuronal cell groups residing within the retrotrapezoid nucleus (RTN) and C1 area of the rostral ventrolateral medulla oblongata contribute to the maintenance of resting respiratory activity and arterial blood pressure, and play an important role in the development of cardiorespiratory responses to metabolic challenges (such as hypercapnia and hypoxia). In rats, acute silencing of neurons within the parafacial region which includes the RTN and the rostral aspect of the C1 circuit (pFRTN/C1), transduced to express HM4D (Gi-coupled) receptors, was found to dramatically reduce exercise capacity (by 60%), determined by an intensity controlled treadmill running test. In a model of simulated exercise (electrical stimulation of the sciatic or femoral nerve in urethane anaesthetised spontaneously breathing rats) silencing of the pFRTN/C1 neurons had no effect on cardiovascular changes, but significantly reduced the respiratory response during steady state exercise. These results identify a neuronal cell group in the lower brainstem which is critically important for the development of the respiratory response to exercise and, determines exercise capacity.

Release of ATP by pre-Bötzinger complex astrocytes contributes to the hypoxic ventilatory response via a Ca2+ -dependent P2Y1 receptor mechanism.

The ventilatory response to reduced oxygen (hypoxia) is biphasic, comprising an initial increase in ventilation followed by a secondary depression. Our findings indicate that, during hypoxia, astrocytes in the pre-Bötzinger complex (preBötC), a critical site of inspiratory rhythm generation, release a gliotransmitter that acts via P2Y1 receptors to stimulate ventilation and reduce the secondary depression. In vitro analyses reveal that ATP excitation of the preBötC involves P2Y1 receptor-mediated release of Ca2+ from intracellular stores. By identifying a role for gliotransmission and the sites, P2 receptor subtype, and signalling mechanisms via which ATP modulates breathing during hypoxia, these data advance our understanding of the mechanisms underlying the hypoxic ventilatory response and highlight the significance of purinergic signalling and gliotransmission in homeostatic control. Clinically, these findings are relevant to conditions in which hypoxia and respiratory depression are implicated, including apnoea of prematurity, sleep disordered breathing and congestive heart failure. The hypoxic ventilatory response (HVR) is biphasic, consisting of a phase I increase in ventilation followed by a secondary depression (to a steady-state phase II) that can be life-threatening in premature infants who suffer from frequent apnoeas and respiratory depression. ATP released in the ventrolateral medulla oblongata during hypoxia attenuates the secondary depression. We explored a working hypothesis that vesicular release of ATP by astrocytes in the pre-Bötzinger Complex (preBötC) inspiratory rhythm-generating network acts via P2Y1 receptors to mediate this effect. Blockade of vesicular exocytosis in preBötC astrocytes bilaterally (using an adenoviral vector to specifically express tetanus toxin light chain in astrocytes) reduced the HVR in anaesthetized rats, indicating that exocytotic release of a gliotransmitter within the preBötC contributes to the hypoxia-induced increases in ventilation. Unilateral blockade of P2Y1 receptors in the preBötC via local antagonist injection enhanced the secondary respiratory depression, suggesting that a significant component of the phase II increase in ventilation is mediated by ATP acting at P2Y1 receptors. In vitro responses of the preBötC inspiratory network, preBötC inspiratory neurons and cultured preBötC glia to purinergic agents demonstrated that the P2Y1 receptor-mediated increase in fictive inspiratory frequency involves Ca2+ recruitment from intracellular stores leading to increases in intracellular Ca2+ ([Ca2+ ]i ) in inspiratory neurons and glia. These data suggest that ATP is released by preBötC astrocytes during hypoxia and acts via P2Y1 receptors on inspiratory neurons (and/or glia) to evoke Ca2+ release from intracellular stores and an increase in ventilation that counteracts the hypoxic respiratory depression.

The role of GαO-mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability.

The heart is controlled by the sympathetic and parasympathetic limbs of the autonomic nervous system with inhibitory signaling mechanisms recruited in both limbs. The aim of this study was to determine the role of inhibitory heterotrimeric G proteins in the central nervous mechanisms underlying autonomic control of the heart and its potential role in arrhythmogenesis. Mice with conditional deletion of the inhibitory heterotrimeric G protein Gα O in the presympathetic area of the rostral ventral lateral medulla (RVLM) were generated to determine the role of GαO‐mediated signalling in autonomic control and electrophysiological properties of the heart. Gα O deletion within the RVLM was not associated with changes in heart rate (HR) or the arterial blood pressure at rest (home cage, normal behavior). However, exposure to stressful conditions (novel environment, hypoxia, or hypercapnia) in these mice was associated with abnormal HR responses and an increased baroreflex gain when assessed under urethane anesthesia. This was associated with shortening of the ventricular effective refractory period. This phenotype was reversed by systemic beta‐adrenoceptor blockade, suggesting that Gα O depletion in the RVLM increases central sympathetic drive. The data obtained support the hypothesis that Gα O‐mediated signaling within the presympathetic circuits of the RVLM contributes to the autonomic control of the heart. Gα O deficiency in the RVLM has a significant impact on cardiovascular responses to stress, cardiovascular reflexes and electrical properties of the heart.

Glia, sympathetic activity and cardiovascular disease.

New Findings What is the topic of this review? In this review, we discuss recent findings that provide a novel insight into the mechanisms that link glial cell function with the pathogenesis of cardiovascular disease, including systemic arterial hypertension and chronic heart failure. What advances does it highlight? We discuss how glial cells may influence central presympathetic circuits, leading to maladaptive and detrimental increases in sympathetic activity and contributing to the development and progression of cardiovascular disease. Increased activity of the sympathetic nervous system is associated with the development of cardiovascular disease and may contribute to its progression. Vasomotor and cardiac sympathetic activities are generated by the neuronal circuits located in the hypothalamus and the brainstem. These neuronal networks receive multiple inputs from the periphery and other parts of the CNS and, at a local level, may be influenced by their non‐neuronal neighbours, in particular glial cells. In this review, we discuss recent experimental evidence suggesting that astrocytes and microglial cells are able to modulate the activity of sympathoexcitatory neural networks in disparate physiological and pathophysiological conditions. We focus on the chemosensory properties of astrocytes residing in the rostral ventrolateral medulla oblongata and discuss signalling mechanisms leading to glial activation during brain hypoxia and inflammation. Alterations in these mechanisms may lead to heightened activity of sympathoexcitatory CNS circuits and contribute to maladaptive and detrimental increases in sympathetic tone associated with systemic arterial hypertension and chronic heart failure.

Neurovascular compression of medulla oblongata – Association for gestation-induced hypertension

Patients with essential hypertension may show neurovascular compression (NVC) at the rostral ventrolateral medulla oblongata (RVLM). Ectatic loops of the vertebral artery (VA) or the inferior posterior cerebellar artery (PICA) cause NVC. This study aims to show the existence and morphology of NVC in patients with gestation-induced hypertension. 17 females were prospectively examined between 19+0 and 35+6weeks of gestation. 3 patients with chronic hypertension (group A), 10 patients with preeclampsia (group B), 3 patients with superimposed preeclampsia (chronic hypertension with preeclampsia; group C) and one normotensive patient were included. Groups B and C represented patients with gestation-induced hypertension. All 17 patients underwent imaging by high resolution magnetic resonance imaging (MR-CISS, constructive interference in the steady state). Image processing was done with segmentation and three-dimensional (3D)-visualization was implemented with direct volume rendering of the individual neurovascular details of each patient. 9 of 17 patients (53%) showed NVC of the RVLM. Right-sided NVC was seen in 7 patients (41%). Left-sided NVC was seen in 6 patients (35%). Bilateral NVC was seen in 4 patients (24%). NVC was missing in 8 of the examined 17 patients (47%). The existence of NVC with high-resolution MRI was analyzed in gestation-induced hypertensive pregnant females for the first time. Neurovascular conflicts were seen in hypertensive pregnants. It is possible that NVC is potentially associated in patients with gestation-induced hypertension.

Brainstem hypoxia contributes to the development of hypertension in the spontaneously hypertensive rat.

Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O2 sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal PO2 in the spontaneously hypertensive rat was found to be ≈15 mm Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower PO2 of brainstem parenchyma may be associated with higher levels of ambient ATP and l-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure.

Independent purinergic mechanisms of central and peripheral chemoreception in the rostral ventrolateral medulla.

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.

Effect of edaravone on acute brainstem–cerebellar infarction with vertigo and sudden hearing loss

We report 2 cases with acute brainstem and brainstem-cerebellar infarction showed improvement of their signs and symptoms after administration of edaravone. Case 1, a 74-year-old woman who experienced sudden vertigo, also had dysarthria and left hemiplegia. Magnetic resonance imaging (MRI) showed an abnormal region in the right ventrolateral medulla oblongata. The patient's vertigo and hemiplegia improved completely after treatment. Case 2, a 50-year-old man who experienced sudden vertigo and sensorineural hearing loss (SNHL), developed dysarthria after admission. MRI revealed acute infarction in the right cerebellar hemisphere. Magnetic resonance angiography revealed dissection of the basilar artery and occlusion of the right anterior inferior cerebellar artery. The patient's vertigo and hearing remarkably improved. We have described 2 patients whose early symptoms were vertigo and sudden SNHL, but who were later shown to have ischemic lesions of the central nervous system. Edaravone is neuroprotective drug with free radical-scavenging actions. Free radicals in the ear are responsible for ischemic damage. Edaravone, a free radical scavenger, may be useful in the treatment of vertigo and SNHL.

The role of GalphaO-mediated signalling in the central nervous mechanisms controlling sympathetic outflow to the heart

Purpose: Inhibitory G proteins are known to mediate vagal influences on the heart. However, their role in the central nervous mechanisms of cardiovascular control remain unclear. We hypothesised that in mice, conditional deletion of GalphaO (GαO) in the rostral ventrolateral medulla oblongata (RVLM), which contains sympathoexcitatory (pre-sympathetic) neurones, will have a significant impact on autonomic cardiac reflexes. Methods: Using the Cre/LoxP approach, GαO was deleted in the RVLM of GαO flx/flx mice aged between 8 to 12 weeks (CKO) by stereotaxic delivery of an adenoviral (AdV) vector to trigger expression of Cre and GFP driven by a CMV promoter. Littermates injected with a GFP-only-expressing AdV served as controls. After 1 week, these mice (under urethane anaesthesia, 1.3 g/kg IP) were given alternating doses of phenylephrine (0.5-2mg/kg, IV) and sodium nitroprusside (0.1-1mg/kg, IV) and the obtained heart rate (HR) and blood pressure (BP) data were used to individually fit sigmoidal baroreflex curves (Fig 1). The animals were then sacrificed and transgene expression was confirmed histologically. Results: Compared to controls, CKO mice (n=4 in each group) were tachycardic (median minimum HR 608 bpm, IQR 604-639 vs 580 bpm, IQR 576-598) and displayed an increased baroreflex gain (mean BR gain 0.65 bpm/mmHg, 95% CI 0.46-0.83 vs 0.35 bpm/mmHg, 95% CI 0.33-0.37, p=0.03). Figure 1: Baroreflex curves Figure 1: Baroreflex curves Conclusion: Mice with conditional deletion of GαO within the sympathoexcitatory circuits of the brainstem display enhanced baroreflex sensitivity consistent with an increased sympathetic tone. This suggests an important role for GαO-mediated signalling in the central nervous inhibitory mechanisms controlling sympathetic outflow.

Expression of phospho-Ca2+ /calmodulin-dependent protein kinase II in the pre-Bötzinger complex of rats

The pre-Bötzinger complex (pre-BötC) in the ventrolateral medulla oblongata is a presumed kernel of respiratory rhythmogenesis. Ca(2+) -activated non-selective cationic current is an essential cellular mechanism for shaping inspiratory drive potentials. Ca(2+) /calmodulin-dependent protein kinase II (CaMKII), an ideal 'interpreter' of diverse Ca(2+) signals, is highly expressed in neurons in mediating various physiological processes. Yet, less is known about CaMKII activity in the pre-BötC. Using neurokinin-1 receptor as a marker of the pre-BötC, we examined phospho (P)-CaMKII subcellular distribution, and found that P-CaMKII was extensively expressed in the region. P-CaMKII-ir neurons were usually oval, fusiform, or pyramidal in shape. P-CaMKII immunoreactivity was distributed within somas and dendrites, and specifically in association with the post-synaptic density. In dendrites, most synapses (93.1%) examined with P-CaMKII expression were of asymmetric type, occasionally with symmetric type (6.9%), whereas in somas, 38.1% were of symmetric type. P-CaMKII asymmetric synaptic identification implicates that CaMKII may sense and monitor Ca(2+) activity, and phosphorylate post-synaptic proteins to modulate excitatory synaptic transmission, which may contribute to respiratory modulation and plasticity. In somas, CaMKII acts on both symmetric and asymmetric synapses, mediating excitatory and inhibitory synaptic transmission. P-CaMKII was also localized to the perisynaptic and extrasynaptic regions in the pre-BötC.

196 ATP-MEDIATED SIGNALLING IN THE PRE-SYMPATHETIC AREA OF THE BRAINSTEM IS CRITICAL FOR THE DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

Introduction Increased sympathetic drive is associated with the development and progression of essential hypertension. Pharmacological studies have shown a direct stimulatory effect of ATP on bulbospinal sympathoexcitatory (pre-sympathetic) neurones of the rostral ventrolateral medulla oblongata (RVLM), leading to marked increases in sympathetic nerve activity and arterial blood pressure (BP). The aim of this study was to determine whether ATP actions within the RVLM contribute to the control of arterial BP in normotensive and hypertensive rats. Methods We developed a lentiviral vector (LVV) to drive the expression of a potent membrane-bound ectonucleotidase “transmembrane prostatic acid phosphatase (TMPAP) for facilitated breakdown of extracellular ATP. LVV-TMPAP or control LVV-GFP were injected stereotaxically into the RVLM of pre-hypertensive (8-weeks-old) spontaneously hypertensive rats (SHRs) and age-matched Wistar rats. BP measurements were performed by occlusive tail cuff method. Measurements were commenced 1 week after the injections and repeated weekly for 4 weeks. Results Expression of TMPAP in the RVLM of SHRs resulted in a significant reduction in arterial BP. Three weeks after the injections, SHRs transduced to express TMPAP in the RVLM had mean arterial BP of 115.6±8.8 mmHg (n=7), which was significantly (p=0.009) lower than that in SHRs transduced to express GFP (152.9±8.4 mmHg, n=9). In comparison, TMPAP expression in the RVLM had no significant effect on the mean arterial BP of control Wistar rats (91.4±4.5 vs 92.6±3.5 mmHg, p=0.836, n=8 in both groups). Conclusion Increased breakdown of extracellular ATP in the brainstem area where the key sympathoexcitatory neurones reside reduces the degree of hypertension in the SHR. These data suggest that ATP-mediated signalling has a significant impact on brain pre-sympathetic circuits and appears to be critical for the development of essential hypertension.

223 THE ROLE OF INHIBITORY G PROTEIN GALPHAO-MEDIATED SIGNALLING IN THE CENTRAL NERVOUS MECHANISMS CONTROLLING SYMPATHETIC OUTFLOW TO THE HEART

<h3>Introduction</h3> Inhibitory G proteins are known to mediate vagal influences on the heart. However, their role in the central nervous mechanisms of cardiovascular control remain unclear. Previous data have shown mice with global deletion of GalphaO (GαO) exhibit tachycardia, loss of diurnal variation and fairly selective loss of LF component of HRV with preserved total power suggestive of increased sympathetic tone, likely to be of central origin. We hence hypothesised that in mice, conditional deletion of GalphaO (GαO) in the rostral ventrolateral medulla oblongata (RVLM), which contains sympathoexcitatory (pre-sympathetic) neurones, will have a significant impact on autonomic cardiac reflexes. <h3>Methods</h3> Using the Cre/LoxP approach, GαO was deleted in the RVLM of GαO flx/flx mice aged between 8 to 12 weeks (CKO) by stereotaxic delivery of an adenoviral (AdV) vector to trigger expression of Cre and GFP driven by a CMV promoter. Littermates injected with a GFP-only-expressing AdV served as controls. After 1 week, these mice (under urethane anaesthesia, 1.3 g/kg IP) were given alternating doses of phenylephrine (0.5-2mg/kg, IV) and sodium nitroprusside (0.1-1mg/kg, IV) and the obtained heart rate (HR) and blood pressure (BP) data were used to individually fit sigmoidal baroreflex curves (Figure&nbsp;1). The animals were then sacrificed and transgene expression was confirmed histologically. <h3>Results</h3> Compared to controls, CKO mice (n=4 in each group) were tachycardic (median minimum HR 608 bpm, IQR 604-639 vs 580 bpm, IQR 576-598) and displayed an increased baroreflex gain (mean BR gain 0.65 bpm/mmHg, 95% CI 0.46-0.83 vs 0.35 bpm/mmHg, 95%CI 0.33-0.37, p=0.03). <h3>Conclusion</h3> Mice with conditional deletion of GαO within the sympathoexcitatory circuits of the brainstem display enhanced baroreflex sensitivity consistent with an increased sympathetic tone. This suggests an important role for GαO-mediated signalling in the central nervous inhibitory mechanisms controlling sympathetic outflow.

Chiari I malformation with neurogenic hypertension: case report

Chiari I malformation presents with pain, headache, dizziness, loss of thermal sensitivity, and changes in strength in the limbs. This occurs due to the involvement of the anatomical structures underlying the occipitocervical junction such as the lower cranial nerves, cerebellum, and major ascending and descending pathways. There is a lack of studies that investigate the association between neurogenic hypertension and Chiari I malformation [1]. The studies that exist have shown the connection between hypertension and vascular compression of neural structures at the brainstem, particularly the rostral ventrolateral medulla oblongata. This association suggests that other compressions of the medulla oblongata can present with elevated blood pressure by a similar mechanism [2, 3]. We report a case of a patient with chronic arterial hypertension without classic signs of Chiari with resolution after decompressive surgery. It seems to be the first case reported in Brazil.

Synaptic relationship between somatostatin‐ and neurokinin‐1 receptor‐immunoreactive neurons in the pre‐Bötzinger complex of rats

The pre-Bötzinger complex (pre-BötC) in the ventrolateral medulla oblongata is critical for the generation of respiratory rhythm in mammals. Somatostatin (SST) and neurokinin 1 receptor (NK1R) immunoreactivity have been used as markers of the pre-BötC. SST immunoreactivity almost completely overlaps with small fusiform NK1R-immunoreactive (ir) neurons, the presumed rhythmogenic neurons, but not with large multipolar NK1R-ir neurons. Understanding the neurochemical characteristics, especially the synaptic relationship of SST/NK1R-ir neurons within the pre-BötC network is essential in providing cellular and structural bases for understanding their physiological significance. This work has not been documented so far. We found that SST immunoreactivity was highly expressed in terminals, somas, and primary dendrites in the pre-BötC. Besides the small fusiform neurons, a small population of medium-sized NK1R-ir neurons also colocalized with SST. Large NK1R-ir neurons were not SST-ir, but received somatostatinergic inputs. SST-ir terminals were glutamatergic or GABAergic, and synapsed with NK1R-ir neurons. Most of synapses between them were of the symmetric type, indicating their inhibitory nature. Asymmetric synapses were evident between SST-ir terminals and NK1R-ir dendrites, strongly suggesting an excitatory innervation from the presumed rhythmogenic neurons as these neurons are glutamatergic. We speculate that SST-mediated excitatory and inhibitory synaptic transmission onto NK1R-ir rhythmogenic and follower neurons synchronizes their activity to contribute to respiratory rhythmogenesis and control.

Nuclear organization of the serotonergic system in the brain of the rock cavy (Kerodon rupestris)

Serotonin, or 5-hydroxytryptamine (5-HT), is a substance found in many tissues of the body, including as a neurotransmitter in the nervous system, where it can exert different post-synaptic actions. Inside the neuro-axis, 5-HT neurons are almost entirely restricted to the raphe nuclei of the brainstem. As such, 5-HT-immunoreactivity has been considered a marker of the raphe nuclei, which are located in the brainstem, at or near the midline. The present study investigated distribution of serotonergic neurons in the brain of the rock cavy (Kerodon rupestris), a rodent species inhabiting the Brazilian Northeast. The cytoarchitectonic location of serotonergic neurons was established through a series of 5-HT immunostained sections, compared with diagrams obtained from adjacent coronal and sagittal sections stained by the Nissl method. The following nuclei were defined: the rostral group, consisting of rostral linear raphe, caudal linear raphe, median and paramedian raphe, dorsal raphe, and pontine raphe nuclei, and the caudal group composed of raphe magnus, raphe pallidus and raphe obscurus nuclei. Other serotonergic neuronal clusters, such as the supralemniscal group and the rostral and caudal ventrolateral medulla oblongata clusters, were found outside the midline. Rare 5-HT-producing neurons were identified in the lateral parabrachial nucleus and in the pontine reticular formation, mostly along fibers of the lateral lemniscus. Despite exhibiting some specializations, the picture outlined for serotonergic groups in the rock cavy brain is comparable to that described for other mammalian species.

Brainstem galanin‐synthesizing neurons are differentially activated by chemoreceptor stimuli and represent a subpopulation of respiratory neurons

The ventrolateral medulla oblongata (VLM) of the brainstem contains neurochemically heterogeneous neurons that have a critical role in cardiovascular and respiratory regulation. Previous anatomical studies have shown the existence of galanin immunoreactivity in the medulla oblongata, but a detailed characterization is lacking. In this study, we demonstrate three populations of preprogalanin mRNA (PPG)-expressing neurons in the VLM of the adult, male Sprague-Dawley rat: a retrotrapezoid nucleus (RTN) group, a group in the rostral ventral respiratory group (rVRG), and a subpopulation of A1 neurons. PPG(+) neurons express tyrosine hydroxylase (TH) only in the A1 region of the VLM, where approximately 56% of PPG(+) neurons contain TH (79 ± 14; n = 4). PPG(+) neurons do not express vesicular acetylcholine transporter (vAChT) in the VLM (n = 3). However, 33% of PPG(+) neurons contain neurokinin-1 receptor (NK1R) in the rVRG (126 ± 12; n = 12), accounting for ∼28% of all NK1R(+) neurons in the region. Retrogradely transported cholera toxin B injected into the thoracic spinal cord (T1) revealed that bulbospinal PPG(+) neurons are present in the rVRG (n = 3; ∼26% of PPG(+) neurons). PPG(+) neurons in the RTN and locus coeruleus are selectively activated (Fos) following 2 hours of exposure to hypercapnia, but not by hypoxia. Neurons in the A1, nucleus of the solitary tract, and dorsomedial hypothalamus are activated by both chemoreceptor stimuli. The results suggest that PPG(+) neurons represent a population of brainstem neurons that play a critical and differential role in the chemoreflex responses to hypoxia and hypercapnia.

Primary hypertension and neurovascular compression: a meta-analysis of magnetic resonance imaging studies

Several studies have suggested that neurovascular compression (NVC) of the brainstem might be a cause of hypertension. Because this compression syndrome might be demonstrated by MR imaging studies, several authors have tried to assess its prevalence in small series of patients with hypertension. This article presents a meta-analysis of these studies. The studies reviewed by the authors were based on MR imaging and included the presence of left-sided NVC of the left rostral ventrolateral medulla oblongata (RVLM) and/or the cranial nerves IX and X root entry zone in patients with apparent primary hypertension compared with normotensive patients. Several studies also included patients with secondary hypertension as an additional control group, which is analyzed separately. Meta-analysis included data from 14 studies (597 patients with primary hypertension and 609 controls). The effect size was OR 2.68 (95% CI 1.51-4.75, p = 0.001) (random effect), which is consistent with the hypothesis that NVC of the left RVLM is more frequent in patients with apparent primary hypertension compared with normotensive individuals. Stratification for the study design revealed an effect size for prospective studies of OR 1.97 (95% CI 0.74-5.30, p = 0.178) and for retrospective studies of OR 3.36 (95% CI 1.66-6.79, p = 0.001). This meta-analysis indicates a statistically significant effect size for left-sided NVC in apparent primary hypertension. However, this effect is absent if subanalysis is confined to prospective studies.

Blood Pressure Patterns After Brain Death

The control of vasomotor tone by the rostral ventrolateral medulla oblongata is lost in brain death. Hypotension is not an obligate clinical sign in brain death criteria, because an adequate intravascular volume may temporarily overcome this decrease in blood pressure. However, such an unstable situation is bound to collapse.1,2 Anticipatory knowledge of changes in blood pressure is important to physicians who perform brain death examinations. Delay in declaration of brain death in a hemodynamically unstable patient may jeopardize procurement and prompt pharmaceutical support to maintain adequate blood pressures is required.3,–,5 We aimed to characterize hemodynamic patterns after brain death. We identified patients from a database maintained by our organ procurement organization (LifeSource). Brain death was declared according to a hospital protocol in compliance with the American Academy of Neurology guidelines.6 The use of methylprednisolone and T4 infusions was standardized in 2005. We excluded patients who did not undergo organ procurement and died quickly after admission, and young children (<10 years old). The records of patients who were declared brain dead from 1997 to 2010 were retrospectively reviewed. Blood …