大鼠孤束核内5-HT能纤维和终末与向臂旁核投射的NOS阳性神经元的联系

应用四甲基罗达明逆行标记和免疫荧光技术相结合 ,在激光扫描共聚焦显微镜下对大鼠孤束核内 5 -HT能纤维和终末与向臂旁核投射的 NOS阳性神经元之间的联系进行了观察。将四甲基罗达明注入一侧外侧臂旁核后可见孤束核尾段背内侧、胶质、小细胞、内侧、中间内侧等亚核和连合亚核内出现较多的逆标神经元 ,四甲基罗达明逆标和 NOS阳性神经元以及 5 -HT阳性终末重叠分布 ,其中四甲基罗达明和 NOS双重阳性神经元分别占四甲基罗达明逆标和 NOS阳性神经元总数的 8.3% ( 14 /16 8)和 18.4% ( 14 /76 )。在此 5 -HT样阳性纤维和终末包绕着 NOS阳性神经元、四甲基罗达明逆标神经元及四甲基罗达明和一氧化氮合酶双重阳性神经元的胞体和树突 ,形成点状紧密接触。本研究结果提示 ,孤束核内来自下行性抑制系统的 5 -HT能纤维和终末可能与向臂旁核投射的 NOS阳性神经元形成突触联系 ,从而可对 NOS阳性神经元所传递的包括伤害性信息在内的内脏感觉传入信息发挥抑制性调控作用     

Coexistence of NMDA and AMPA receptor subunits with nNOS in the nucleus tractus solitarii of rat

We previously showed that most neuronal nitric oxide synthase (nNOS)-containing neurons in the nucleus tractus solitarii (NTS) contain NMDAR1, the fundamental subunit for functional N-methyl-D-aspartate (NMDA) receptors. Likewise, we found that almost all nNOS-containing neurons in the NTS contain GluR1, the calcium permeable AMPA receptor subunit. These data suggest that AMPA and NMDA receptors may colocalize in NTS neurons that contain nNOS. However, other investigators have suggested that non-NMDA receptors are located primarily on second-order neurons and NMDA receptors are located predominantly on higher-order neurons in NTS. We now seek to test the hypothesis that NMDA receptors, AMPA receptors and nNOS are colocalized in NTS cells. We performed triple fluorescent immunohistochemical staining of nNOS, NMDAR1 and GluR1, and performed confocal laser scanning microscopic analysis of the NTS. The distributions of nNOS immunoreactivity (IR), NMDAR1-IR and GluR1-IR in the NTS were similar to those we reported earlier. Superimposed images revealed that almost all NMDAR1-IR cells contained GluR1-IR and almost all GluR1-IR cells contained NMDAR1-IR. Some double-labeled cells were additionally labeled for nNOS-IR. All nNOS-IR neurons contained both GluR1-IR and NMDAR1-IR. These studies support our hypothesis that NMDA and AMPA receptors are colocalized in NTS neurons and are consistent with a role of both types of ionotropic receptors in transmission of afferent signals in NTS. In addition, these data provide support for an anatomical link between ionotropic glutamate receptors and nitric oxide in the NTS.     

Convergence of hepatoportal glucose-sensitive afferent signals to glucose-sensitive units within the nucleus of the solitary tract

Units which are activated by ascending impulses from the liver within the nucleus of the solitary tract (NTS) were identified by electrical stimulation delivered to the hepatic branch of the vagus. Responses of descending units were eliminated by a collision test. The units which showed decreased firing rates during portal infusion of isotonic glucose solution were also glucose-sensitive so that they showed decreased firing rates during topical application of glucose by means of micro-electro-osmotic techniques. It is concluded that glucose-sensitive neurons exist within the NTS and also that they are functionally linked with hepatoportal glucose-sensitive afferent units.     

Extra-hypothalamic afferent inputs to the supraoptic nucleus area of the rat as determined by retrograde and anterograde tracing techniques

To detect neuronal cell bodies whose axon projects to the hypothalamic supraoptic nucleus, small volumes (10-50 nl) of 30% horseradish peroxidase or 2% fast blue solutions were pressure-injected into the area of one supraoptic nucleus of rats. Both dorsal and ventral approaches to the nucleus were used. In animals where the injection site extended beyond the limits of the supraoptic nucleus, retrogradely labelled cell bodies were found in many areas of the brain, mainly in the septum, the nucleus of the diagonal band of Broca and ventral subiculum in the limbic system; the dorsal raphe nucleus, the locus coeruleus, the nucleus of the dorsal tegmentum, the dorsal parabrachial nucleus, the nucleus of the solitary tract and the catecholaminergic A1 region in the brain stem; in the subfornical organ and the organum vasculosum of the lamina terminalis, as well as in the median preoptic nucleus. In contrast, when the site of injection was apparently restricted to the supraoptic nucleus, labelling was only clearcut in the two circumventricular organs, the median preoptic nucleus, the nucleus of the solitary tract and the A1 region. Injections of wheat germ agglutinin coupled with horseradish peroxidase (60-80 nl of a 2.5% solution) made in the septum and in the ventral subiculum anterogradely labelled fibers coursing in an area immediately adjacent to the supraoptic nucleus but not within it. In contrast, labelling within the nucleus was found following anterograde transport of tracer deposited in the A1 region and in an area that includes the nucleus of the solitary tract. Neurones located in the perinuclear area were densely labelled by small injections into the supraoptic nucleus; they may represent a relay station for some afferent inputs to the supraoptic nucleus. These results suggest that the supraoptic nucleus is influenced by the same brain areas which project to its companion within the magnocellular system, the paraventricular nucleus.     

Preventable death in trauma: A systematic review on definition and classification

PurposeTrauma-related preventable death (TRPD) has been used to assess the management and quality of trauma care worldwide. However, due to differences in terminology and application, the definition of TRPD lacks validity. The aim of this systematic review is to present an overview of current literature and establish a designated definition of TRPD to improve the assessment of quality of trauma care.MethodsA search was conducted in PubMed, Embase, the Cochrane Library and the Web of Science Core Collection. Including studies regarding TRPD, published between January 1, 1990, and April 6, 2021. Studies were assessed on the use of a definition of TRPD, injury severity scoring tool and panel review.ResultsIn total, 3,614 articles were identified, 68 were selected for analysis. The definition of TRPD was divided in four categories: I. Clinical definition based on panel review or expert opinion (TRPD, trauma-related potentially preventable death, trauma-related non-preventable death), II. An algorithm (injury severity score (ISS), trauma and injury severity score (TRISS), probability of survival (Ps)), III. Clinical definition completed with an algorithm, IV. Other. Almost 85% of the articles used a clinical definition in some extend; solely clinical up to an additional algorithm. A total of 27 studies used injury severity scoring tools of which the ISS and TRISS were the most frequently reported algorithms. Over 77% of the panels included trauma surgeons, 90% included other specialist; 61% emergency medicine physicians, 46% forensic pathologists and 43% nurses.ConclusionThe definition of TRPD is not unambiguous in literature and should be based on a clinical definition completed with a trauma prediction algorithm such as the TRISS. TRPD panels should include a trauma surgeon, anesthesiologist, emergency physician, neurologist, and forensic pathologist.     

Release of endogenous catecholamines in two different regions of the nucleus of the solitary tract as influenced by carotid occlusion

Summary The effects of carotid occlusion on the release of catecholamines in the nucleus of the solitary tract (NTS) were investigated in anaesthetized cats. Two aspects of the nucleus (rostral or intermediate NTS) were superfused bilaterally through push-pull cannulae with artificial CSF and the release of the endogenous dopamine, noradrenaline and adrenaline was determined in the superfusate radioenzymatically. The superfusion rate was 150 l/min or 800 l/min. In some experiments, superfusion of the intermediate NTS was carried out after denervation of the aortic arch.In the rostral NTS superfused at a rate of 150 l/min, bilateral carotid occlusion led to a rise in blood pressure and decreased the release rate of dopamine. These changes continued after occlusion termination. The release rate of noradrenaline was transiently diminished during occlusion. The release of this amine was also decreased after occlusion termination. The release rate of adrenaline was not influenced during carotid occlusion, but it was found to be diminished after termination of the occlusion. Superfusion of the rostral NTS at a rate of 800 l/min also reduced the release rate of adrenaline after termination of carotid artery occlusion. In the intermediate NTS (superfusion rate 150 l/min) similar effects of the carotid occlusion on the release rates of dopamine and noradrenaline were observed. In this aspect of the NTS, denervation of the aortic arch abolished the decrease in the noradrenaline release during carotic occlusion, while the release rates of dopamine and adrenaline were decreased during and after termination of the carotid occlusion.The results suggest that (a) the rise in blood pressure in the carotid sinus after termination of a carotid occlusion decreases the release rates of noradrenaline and adrenaline in the NTS, (b) the decrease in the release of noradrenaline during carotid occlusion is due to impulses originating from the baroreceptors of the aortic arch.Thus, impulses from carotid sinus and aortic arch modify the release rates of noradrenaline in the NTS so as to counteract blood pressure changes.Supported by the Fonds zur Förderung der wissenschaftlichen Forschung Send offprint requests to A. Philippu at the above address     

Blood pressure changes modify the release rates of catecholamines in the intermediate nucleus of the solitary tract

Summary In anaesthetized cats, the intermediate aspect of the nucleus of the solitary tract (NTS) was bilaterally superfused with artificial CSF through push-pull cannulae. The release of the endogenous catecholamines dopamine, noradrenaline and adrenaline was determined in the superfusates radioenzymatically. Blood pressure changes were elicited by intravenous injections of drugs (noradrenaline or chlorisondamine), or electrical stimulation of the intermediate NTS with the tip of the push-pull cannula.Intravenous injections of noradrenaline (3 or 10 g/kg) elicited a rise in the arterial blood pressure which was associated with a decrease in the release rate of adrenaline in the intermediate NTS. The release rates of dopamine and noradrenaline were not influenced. The intravenous injection of chlorisondamine (3 mg/kg) lowered blood pressure and diminished the release rate of dopamine in the intermediate NTS. The release rate of noradrenaline was not modified by chlorisondamine. Electrical stimulation of the intermediate NTS contralateral to the superfused nucleus increased moderately the arterial blood pressure and decreased the release rate of noradrenaline and dopamine, while the release of adrenaline was not influenced. The findings suggest that experimentally induced changes in the arterial blood pressure by drugs injected intravenously modify the release rates of adrenaline and dopamine in the intermediate NTS so as to counteract the blood pressure change. In the intermediate NTS, release of adrenaline from adrenergic nerve terminals seems to act hypertensive. The results obtained with chlorisondamine point to a hypotensive function of endogenous dopamine in the intermediate NTS. Send offprint requests to N. Singewald at the above addressThis work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.     

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

The presence of melanin-concentrating hormone (MCH) containing processes, projecting from the lateral hypothalamus to the medial nucleus tractus solitarius (mNTS), has been reported in the rat. It was hypothesized that MCH acting within the mNTS may modulate the central regulation of cardiovascular function. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of MCH (0.25, 0.5, 0.75, and 1 mM) into the mNTS of anesthetized rats elicited decreases in mean arterial pressure (20.4±1.6, 50.7±3.3, 35.7±2.8 and 30.0±2.6 mm Hg, respectively). The decreases in heart rate in response to these concentrations of MCH were 40.0±8.7, 90.0±13.0, 48.0±7.3 and 48.0±8.0 beats/min, respectively. Maximum cardiovascular responses were elicited by a 0.5 mM concentration of MCH. Cardiovascular responses to MCH were similar in unanesthetized mid-collicular decerebrate rats. Control microinjections of normal saline (100 nl) did not elicit any cardiovascular response. Ipsilateral or bilateral vagotomy significantly attenuated MCH-induced bradycardia. Prior microinjections of PMC-3881-PI (2 mM; MCH-1 receptor antagonist) into the mNTS blocked the cardiovascular responses to microinjections of MCH. Microinjection of MCH (0.5 mM) into the mNTS decreased efferent greater splanchnic nerve activity. Direct application of MCH (0.5 mM; 4 nl) to barosensitive nucleus tractus solitarius (NTS) neurons increased their firing rate. These results indicate that: 1) MCH microinjections into the mNTS activate MCH-1 receptors and excite barosensitive NTS neurons, causing a decrease in efferent sympathetic activity and blood pressure, and 2) MCH-induced bradycardia is mediated via the activation of the vagus nerves.