Neonatal Chlamydia muridarum respiratory infection causes neuroinflammation within the brainstem during the early postnatal period.

Respiratory infections are one of the most common causes of illness and morbidity in neonates worldwide. In the acute phase infections are known to cause wide-spread peripheral inflammation. However, the inflammatory consequences to the critical neural control centres for respiration have not been explored. Utilising a well characterised model of neonatal respiratory infection, we investigated acute responses within the medulla oblongata which contains key respiratory regions. Neonatal mice were intranasally inoculated within 24 h of birth, with either Chlamydia muridarum or sham-infected, and tissue collected on postnatal day 15, the peak of peripheral inflammation. A key finding of this study is that, while the periphery appeared to show no sex-specific effects of a neonatal respiratory infection, sex had a significant impact on the inflammatory response of the medulla oblongata. There was a distinct sex-specific response in the medulla coincident with peak of peripheral inflammation, with females demonstrating an upregulation of anti-inflammatory cytokines and males showing very few changes. Microglia also demonstrated sex-specificity with the morphology of females and males differing based upon the nuclei. Astrocytes showed limited changes during the acute response to neonatal infection. These data highlight the strong sex-specific impact of a respiratory infection can have on the medulla in the acute inflammatory phase.

[Repeated mild traumatic brain injury in the parietal cortex inhibits expressions of NLG-1 and PSD-95 in the medulla oblongata of mice].

OBJECTIVE: To assess the effects of repeated mild traumatic brain injury (rmTBI) in the parietal cortex on neuronal morphology and synaptic plasticity in the medulla oblongata of mice. METHODS: Thirty-two male ICR mice were randomly divided into sham operation group (n=8) and rmTBI group (n=24). The mice in the latter group were subjected to repeated mild impact injury of the parietal cortex by a free-falling object. The mice surviving the injuries were evaluated for neurological deficits using neurological severity scores (NSS), righting reflex test and forced swimming test, and pathological changes of the neuronal cells in the medulla oblongata were observed with HE and Nissl staining. Western blotting and immunofluorescence staining were used to detect the expressions of neuroligin 1(NLG-1) and postsynaptic density protein 95(PSD-95) in the medulla oblongata of the mice that either survived rmTBI or not. RESULTS: None of the mice in the sham-operated group died, while the mortality rate was 41.67% in rmTBI group. The mice surviving rmTBI showed significantly reduced NSS, delayed recovery of righting reflex, increased immobility time in forced swimming test (P < 0.05), and loss of Nissl bodies; swelling and necrosis were observed in a large number of neurons in the medulla oblongata, where the expression levels of NLG-1 and PSD-95 were significantly downregulated (P < 0.05). The mice that did not survive rmTBI showed distorted and swelling nerve fibers and decreased density of neurons in the medulla oblongina with lowered expression levels of NLG-1 and PSD-95 compared with the mice surviving the injuries (P < 0.01). CONCLUSION: The structural and functional anomalies of the synapses in the medulla oblongata may contribute to death and neurological impairment following rmTBI in mice.

Neuroinflammation Plays a Potential Role in the Medulla Oblongata After Moderate Traumatic Brain Injury in Mice as Revealed by Nontargeted Metabonomics Analysis.

Moderate traumatic brain injury (mTBI) involves a series of complex pathophysiological processes in not only the area in direct contact with mechanical violence but also in other brain regions far from the injury site, which may be important factors influencing subsequent neurological dysfunction or death. The medulla oblongata (MO) is a key area for the maintenance of basic respiratory and circulatory functions, whereas the pathophysiological processes after mTBI have rarely drawn the attention of researchers. In this study, we established a closed-head cortical contusion injury model, identified 6 different time points that covered the acute, subacute, and chronic phases, and then used nontargeted metabolomics to identify and analyze the changes in differential metabolites (DMs) and metabolic pathways in the MO region. Our results showed that the metabolic profile of the MO region underwent specific changes over time: harmaline, riboflavin, and dephospho-coenzyme A were identified as the key DMs and play important roles in reducing inflammation, enhancing antioxidation, and maintaining homeostasis. Choline and glycerophospholipid metabolism was identified as the key pathway related to the changes in MO metabolism at different phases. In addition, we confirmed increases in the levels of inflammatory factors and the activation of astrocytes and microglia by Western blot and immunofluorescence staining, and these findings were consistent with the nontargeted metabolomic results. These findings suggest that neuroinflammation plays a central role in MO neuropathology after mTBI and provide new insights into the complex pathophysiologic mechanisms involved after mTBI.

Aberrant dynamic functional network connectivity in progressive supranuclear palsy.

BACKGROUND: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. METHODS: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. RESULTS: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

Recent Research on Mechanisms of Feeding Regulation in Chicks.

Food intake affects poultry productivity. A complete understanding of these regulatory mechanisms provides new strategies to improve productivity. Food intake is regulated by complex mechanisms involving many factors, including the central nervous system, gastrointestinal tract, hormones, and nutrients. Although several studies have been conducted to elucidate regulatory mechanisms in chickens, the mechanisms remain unclear. To update the current knowledge on feeding regulation in chickens, this review focuses on recent findings that have not been summarized in previous reviews, including spexins, adipokines, neurosecretory proteins GL and GM, and central intracellular signaling factors.

Exploring Brainstem Structural Abnormalities: Potential Biomarkers for Panic Disorder.

Panic disorder (PD), characterized by recurrent and intense panic attacks, presents a complex interplay between psychological and neurobiological factors. Although the amygdala and hippocampus have been studied extensively in the context of PD, the brainstem's involvement remains relatively underexplored. This study aims to address this gap by examining structural abnormalities within specific brainstem regions, including the medulla, pons, and midbrain. The study sample population comprised twenty-one adult patients diagnosed with PD and an age-gender-education-matched control group. Utilizing rigorous inclusion and exclusion criteria, confounding factors related to comorbid psychiatric conditions and brain structure abnormalities were minimized. Our findings revealed a significant reduction in medulla volume among PD patients, a finding that persisted even after correcting for individual differences in total intracranial volume. The medulla's role in cardiovascular regulation and autonomic function, coupled with its involvement in fear responses, underscores its potential significance in the pathophysiology of PD. This study elucidates the medulla's structural abnormalities as a potential biomarker for PD. Understanding the role of the brainstem in PD could pave the way for more targeted and effective interventions for this condition.

Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature.

The medulla oblongata is one of the rarest sites of occurrence for germ cell tumors (GCTs) of the central nervous system. As there is scant data regarding epidemiology, clinical presentations, optimal intervention, and long-term prognosis, we aimed to delineate the features of this rare entity by presenting our representative case and performing a quantitative review of the literature. A 24-year-old woman presented to our department with vertigo and swallowing difficulties. Magnetic resonance imaging revealed a homogenously enhanced exophytic lesion arising from the medulla oblongata and extending to the fourth ventricle. Surgical resection was performed and a histological diagnosis of pure germinoma was made. The patient underwent chemotherapy and whole-ventricular irradiation. No recurrence has been experienced for 4 months after the surgery. According to the literature, the prognosis of GCTs at the medulla oblongata seems no worse than those at typical sites. Striking features including occurrence at an older age, female preponderance, and a predominance of germinoma were noteworthy. The pattern of local recurrence suggests extensive radiation coverage is not a prerequisite. Special attention is needed for cardiac and respiratory functions as the main factors eliciting mortality.

Evaluating the Effects of Pulsed Electrical Stimulation on the Mechanical Behavior and Microstructure of Medulla Oblongata Tissues.

The development of remote surgery hinges on comprehending the mechanical properties of the tissue at the surgical site. Understanding the mechanical behavior of the medulla oblongata tissue is instrumental for precisely determining the remote surgery implementation site. Additionally, exploring this tissue's response under electric fields can inform the creation of electrical stimulation therapy regimens. This could potentially reduce the extent of medulla oblongata tissue damage from mechanical compression. Various types of pulsed electric fields were integrated into a custom-built indentation device for this study. Experimental findings suggested that applying pulsed electric fields amplified the shear modulus of the medulla oblongata tissue. In the electric field, the elasticity and viscosity of the tissue increased. The most significant influence was noted from the low-frequency pulsed electric field, while the burst pulsed electric field had a minimal impact. At the microstructural scale, the application of an electric field led to the concentration of myelin in areas distant from the surface layer in the medulla oblongata, and the orderly structure of proteoglycans became disordered. The alterations observed in the myelin and proteoglycans under an electric field were considered to be the fundamental causes of the changes in the mechanical behavior of the medulla oblongata tissue. Moreover, cell polarization and extracellular matrix cavitation were observed, with transmission electron microscopy results pointing to laminar separation within the myelin at the ultrastructure scale. This study thoroughly explored the impact of electric field application on the mechanical behavior and microstructure of the medulla oblongata tissue, delving into the underlying mechanisms. This investigation delved into the changes and mechanisms in the mechanical behavior and microstructure of medulla oblongata tissue under the influence of electric fields. Furthermore, this study could serve as a reference for the development of electrical stimulation regimens in the central nervous system. The acquired mechanical behavior data could provide valuable baseline information to aid in the evolution of remote surgery techniques involving the medulla oblongata tissue.

Attempted Suicide with a Self-Inflicted Penetrating Stab Wound to the Medulla Oblongata Caused by a Pair of Scissors: Case Illustration.

A 78-year-old male patient with a history of psychotic depression was found in the bathroom of his apartment with a pair of scissors driven deeply into the back of his neck. He presented with tetraparesis with residual control over the left lower limb movement. Immediate skull radiograph and brain computed tomography scans revealed the tip of the scissors passing into the foramen magnum. Emergent surgery with midline suboccipital craniectomy and resection of the posterior arch of C1 was performed. The scissors were spontaneously dislocated in the course of surgery. Thereafter, debridement, placement of external ventricular drain and primary closure of the dura and skin were achieved. Post-operatively, the patient was not able to follow any instructions. On the 22nd post-operative day, the patient passed away in palliation. To our knowledge, this is the first reported case of a suicide attempt involving the use of scissors reaching the medulla oblongata.

Changes in myelinated nerve fibers induced by pulsed electrical stimulation: A microstructural perspective on the causes of electrical stimulation side effects.

Electrical brain stimulation technology is widely used in the clinic to treat brain neurological disorders. However, during treatment, patients may experience side effects such as pain, poor limb coordination, and skin rash. Previous reports have focused on the brilliant chapter on electrical brain stimulation technology and have not paid attention to patients' suffering caused by side effects during treatment. In this study, electrodes were arranged on the medulla oblongata. Pulsed electric fields of different frequencies were used to perform electrical stimulation to study the impact of electric fields on myelinated nerve fibers and reveal the possible microstructural origin of side effects. Transmission electron microscopy was used to analyze and quantify the changes in microstructure. The results illustrated that myelinated nerve fibers underwent atrophy under pulsed electric fields, with the mildest degree of atrophy under high-frequency (400 Hz) electric fields. Myelin sheaths experienced plate separation under pulsed electric fields, and a distinct laminar structure appeared. The microstructure changes may be related to the side effects of clinical electrical stimulation. This study can provide pathological possibilities for exploring the causes of the side effects of electrical stimulation and supply guidance for selecting electrical parameters for clinical electrical stimulation therapy from a distinctive perspective.

Development of the human medullary arcuate nucleus from mid-gestation to the perinatal period: A morphometric study.

INTRODUCTION: Development of the human medullary arcuate nucleus (AN) has not been sufficiently investigated. The present study provides morphometric data by examining the brains from preterm and perinatal infants. MATERIALS AND METHODS: Nine brains were obtained from infants aged 21-43 postmenstrual weeks (PW). Serial celloidin sections were cut and stained using the Klüver-Barrera method. After microscopic observations, morphometric parameters [AN volume, numerical density (Nv) and total number (Nt) of neurons, and neuronal profile area (PA)] were analyzed. RESULTS: The AN was found as a pair of neuronal masses on the ventral medullary surface at 21 PW. Caudally, it was ventrolateral to the pyramidal tract (PT), and rostrally, medial to the PT. In the middle, it was diminished in size or interrupted. The AN neurons were gradually enlarged with age, showing multiplicity in size and shape. The following findings had a marked asymmetry and individual variability: (1) complete or partial inclusion of the AN in the PT; (2) connection between the rostral AN and the pontine nuclei; (3) coexistence of pyknotic neurons. The AN volume increased exponentially with age, while the Nv decreased exponentially. The Nt changed along two phases (decrease-increase) after mid-gestation. The mean PA increased linearly with age. Asymmetry and/or individual variability were demonstrated in the AN volume, Nt, and mean PA. CONCLUSIONS: Asymmetry and individual variability in the AN morphology are present in fetal period. The AN may undergo neuron death and neuroblasts production in tandem after mid-gestation.

Possible role of neuropeptide Y on zymosan- and lipopolysaccharide-induced change in gastrointestinal feed passage via the medulla oblongata in chicks.

Zymosan is a fungi-derived pathogen-associated molecular pattern. It activates the immune system and induces the reduction of feed passage rate in the gastrointestinal tract of vertebrates including birds. However, the mechanism mediating the zymosan-induced inhibition of feed passage in the gastrointestinal tract remains unknown. Since the medulla oblongata regulates the digestive function, it is plausible that the medulla oblongata is involved in the zymosan-induced inhibition of feed passage. The present study was performed to identify the genes that were affected by zymosan within the medulla oblongata of chicks (Gallus gallus) using an RNA sequencing approach. We found that mRNAs of several bioactive molecules including neuropeptide Y (NPY) were increased with an intraperitoneal (IP) injection of zymosan. The increase of mRNA expression of NPY in the medulla oblongata was also observed after the IP injection of lipopolysaccharide, derived from gram-negative bacteria. These results suggest that medullary NPY is associated with physiological changes during fungal and bacterial infection. Furthermore, we found that intracerebroventricular injection of NPY and its receptor agonists reduced the feed passage from the crop. Additionally, the injection of NPY reduced the feed passage from the proventriculus to lower digestive tract. NPY also suppressed the activity of duodenal activities of amylase and trypsin. The present study suggests that fungi- and bacteria-induced activation of the immune system may activate the NPY neurons in the medulla oblongata and thereby reduce the digestive function in chicks.

Cholinergic and Nadph-δ neurons in the pedunculopontine and laterodorsal tegmental nuclei of human and nonhuman primates.

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented. The number and density of the labeled neurons were obtained by stringent stereological methods, whereas their topographical distribution was reported upon corresponding magnetic resonance imaging (MRI) planes. In both human and nonhuman primates, the PPN and LDTg are populated by three neurochemically distinct types of neurons (ChAT-/Nadph-δ+, ChAT+/Nadph-δ-, and ChAT+/Nadph-δ+), which are distributed according to a complex spatial interplay. Three-dimensional reconstructions reveal that ChAT+ neurons in the PPN and LDTg form a continuum with some overlaps with pigmented neurons of the locus coeruleus, dorsally, and of the substantia nigra (SN) complex, ventrally. The ChAT+ neurons in the PPN and LDTg are -two to three times more numerous in humans than in monkeys but their density is -three to five times higher in monkeys than in humans. Neurons expressing both ChAT and Nadph-δ have a larger cell body and a longer primary dendritic arbor than singly labeled neurons. Stereological quantification reveals that 25.6% of ChAT+ neurons in the monkey PPN are devoid of Nadph-δ staining, a finding that questions the reliability of Nadph-δ as a marker for cholinergic neurons in primate brainstem.

Neuromyelitis Optica Spectrum Disorder with Sick Sinus Syndrome: Two Cases and a Literature Review.

BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated demyelinating disease of the central nervous system (CNS). There is a lack of reports of sick sinus syndrome (SSS) associated with NMOSD; thus, we hereby report two cases of patients with NMOSD who developed SSS. CASES PRESENTATION: The patients were both male and presented with area postrema syndrome. Brain MRI showed lesions in the dorsal part of their medulla oblongata. They were diagnosed with NMOSD when aquaporin-4 antibodies were found in their serum. Slow heart rates and several episodes of syncope were also observed in case 1 during hospitalization, while Holter monitoring showed sinus pauses (10-11 s) and SSS was diagnosed. A pacemaker was fitted. Case 2 had a respiratory arrest followed by a subsequent cardiac arrest. He was successfully resuscitated with epinephrine injection and cardiopulmonary resuscitation. Through immunotherapy, their neurological functions became stable and heart rate and blood pressure returned to the baseline. CONCLUSIONS: Since sick sinus syndrome is a life-threatening complication, serious heart arrhythmias should be considered as a potential result of area postrema syndrome associated with NMOSD.

Preoperatively difficult-to-diagnose medulla oblongata germinoma: A case report and literature review.

Background: Intracranial germinomas are rare tumors, accounting for 0.5-2% of primary intracranial neoplasms. While they typically occur in the pineal gland, suprasellar region, basal ganglia, and thalamus, germinomas arising in the medulla oblongata are exceptionally rare. Diagnosis of medulla oblongata germinoma is challenging, potentially leading to misdiagnosis and poor prognosis. Case Description: We present a case of a 29-year-old man complaining of left leg numbness. Radiological findings revealed a contrast-enhanced lesion in the medulla oblongata. The patient underwent tumor biopsy, and intraoperative pathological diagnosis (IOD) suspected the diagnosis of medulla oblongata germinoma. He underwent chemoradiotherapy after confirming the diagnosis of germinoma. Intracranial germinoma arising in the medulla oblongata differs from germinomas in other locations due to its higher incidence in individuals in their 20s and a slight female predominance. Conclusion: When encountering lesions in the medulla oblongata, germinoma should be considered as one of the differential diagnoses, and surgical strategies including IOD should be planned accordingly.

Central administered xenin induced Fos expression in nesfatin-1 neurons in rats.

Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system. After the intracerebroventricular administration of xenin on nesfain-1-like immunoreactivity (LI) neurons, we examined its effects on food intake and water intake in rats. As a result, Fos-LI neurons were observed in the organum vasculosum of the laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the arcuate nucleus (Arc), the lateral hypothalamic area (LHA), the central amygdaloid nucleus (CAN), the dorsal raphe nucleus (DR), the locus coeruleus (LC), the area postrema (AP) and the nucleus of the solitary tract (NTS). After the administration, the number of Fos-LI neurons was significantly increased in the LC and the OVLT, the MnPO, the SFO, the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. After the administration of xenin, we conducted double immunohistochemistry for Fos and nesfatin-1, and found that the number of nesfatin-1-LI neurons expressing Fos were significantly increased in the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. The pretreatment of nesfatin-1 antisense significantly attenuated this xenin-induced feeding suppression, while that of nesfatin-1 missense showed no improvement. These results indicate that central administered xenin may have anorexia effects associated with activated central nesfatin-1 neurons.

Insulin Preferentially Regulates the Activity of Parasympathetic Preganglionic Neurons over Sympathetic Preganglionic Neurons.

BACKGRUOUND: Insulin is a peptide hormone that regulates post-prandial physiology, and it is well known that insulin controls homeostasis at least in part via the central nervous system. In particular, insulin alters the activity of neurons within the autonomic nervous system. However, currently available data are mostly from unidentified brainstem neurons of the dorsal motor nucleus of the vagus nerve (DMV). METHODS: In this study, we used several genetically engineered mouse models to label distinct populations of neurons within the brainstem and the spinal cord for whole-cell patch clamp recordings and to assess several in vivo metabolic functions. RESULTS: We first confirmed that insulin directly inhibited cholinergic (parasympathetic preganglionic) neurons in the DMV. We also found inhibitory effects of insulin on both the excitatory and inhibitory postsynaptic currents recorded in DMV cholinergic neurons. In addition, GABAergic neurons of the DMV and nucleus tractus solitarius were inhibited by insulin. However, insulin had no effects on the cholinergic sympathetic preganglionic neurons of the spinal cord. Finally, we obtained results suggesting that the insulininduced inhibition of parasympathetic preganglionic neurons may not play a critical role in the regulation of glucose homeostasis and gastrointestinal motility. CONCLUSION: Our results demonstrate that insulin inhibits parasympathetic neuronal circuitry in the brainstem, while not affecting sympathetic neuronal activity in the spinal cord.

Older adult-onset Alexander disease with atypical clinicoradiological features: a case report.

Alexander disease (AxD) is a rare autosomal dominant astrogliopathy caused by mutations in the gene encoding for glial fibrillary acidic protein. AxD is divided into two clinical subtypes: type I and type II AxD. Type II AxD usually manifests bulbospinal symptoms and occurs in the second decade of life or later, and its radiologic features include tadpole-like appearance of the brainstem, ventricular garlands, and pial signal changes along the brainstem. Recently, eye-spot signs in the anterior medulla oblongata (MO) have been reported in patients with elderly-onset AxD. In this case, an 82-year-old woman presented with mild gait disturbance and urinary incontinence without bulbar symptoms. The patient died 3 years after symptom onset as a result of rapid neurological deterioration after a minor head injury. MRI showed signal abnormalities resembling angel wings in the middle portion of the MO along with hydromyelia of the cervicomedullary junction. Herein, we report the case of this patient with older adult-onset AxD with an atypical clinical course and distinctive MRI findings.

Adult Brainstem Astroblastoma: Unusual Presentation of a Rare Tumor.

Astroblastoma is a rare tumor, which is mostly found in pediatric population. Due to scarcity of literature, the data about treatment is lacking. We are reporting case of brainstem astroblastoma in an adult female. A 45-year-old lady presented with complaint of headache, vertigo, vomiting, and nasal regurgitation for 3 months. On examination, she had weak gag, left hemiparesis. Magnetic resonance imaging brain reported medulla oblongata mass, dorsally exophytic. She underwent suboccipital craniotomy and decompression of mass. Histopathology confirmed diagnosis of astroblastoma. She underwent radiotherapy and recovered well. Brainstem astroblastoma is an extremely rare entity. The surgical resection is possible due to well-defined plane. For best outcome, maximum resection and radiation are indicated.