Search Results (56)

Background: Acute necrotising encephalopathy (ANE) is a rare and severe type of encephalopathy with bilateral symmetrical brain lesions, often following a viral prodrome. ANE type 1 (ANE1) is a disease subtype with a predisposing mutation in the gene encoding RAN binding protein 2 (RANBP2). Methods: We report a case of a 3-year-old girl with clinical symptoms of ANE and brain MRI findings suggesting ANE1, which was subsequently confirmed by genetic analysis. Results: MRI of the brain demonstrated symmetrical high T2/FLAIR signal changes in the lateral geniculate bodies, claustrum, ventromedial thalami, subthalamic nuclei, mamillary bodies, and brainstem, with partly corresponding diffusion restriction, as well as additional haemorrhagic changes in the lateral geniculate bodies on susceptibility weighted imaging. Genetic analysis revealed a heterozygous pathogenic variant of the RANBP2 gene. With immunosuppressive and supportive treatment, the patient fully recovered and was discharged after 10 days in the hospital with no residual symptoms. Conclusions: Recognition of the characteristic MRI findings in ANE1 can facilitate a timely diagnosis and enhance the clinical management of the patient and their relatives, especially given the high risk of disease recurrence. Full article

Background: The central variant of posterior reversible encephalopathy syndrome (cvPRES) is an atypical subtype of PRES. Although no unifying definitions exists, it is most often characterized by vasogenic edema involving “central” structures, such as the brainstem, subcortical nuclei, and spinal cord, with relative sparing of the parieto-occipital lobes. Methods: This systematic review and meta-analysis followed the PRISMA guidelines and was pre-registered on PROSPERO [CRD42023483806]. Both the Joanna Briggs Institute and New-Castle Ottawa scale were used for case reports and cohort studies, respectively. The meta-analysis was completed using R-Studio and its associated “metafor” package. Results: A comprehensive search in four databases yielded 70 case reports/series (n = 100) and 12 cohort studies. The meta-analysis revealed a pooled incidence rate of 13% (95% CI: 9–18%) for cvPRES amongst included cohort studies on PRES. Significant heterogeneity was observed (I² = 71% and a τ² = 0.2046). The average age of affected individuals was 40.9 years, with a slightly higher prevalence in males (54%). The most common etiological factor was hypertension (72%). Fifty percent had an SBP >200 mmHg at presentation and a mean arterial pressure (MAP) of 217.6 ± 40.82. Imaging revealed an increased T₂ signal involving the brain stem (88%), most often in the pons (62/88; 70.45%), and 18/100 (18%) cases of PRES with spinal cord involvement (PRES-SCI). Management primarily involved blood pressure reduction, with adjunctive therapies for underlying causes such as anti-seizure medications or hemodialysis. The MAP between isolated PRES-SCI and cvPRES without spinal cord involvement did not show significant differences (p = 0.5205). Favorable outcomes were observed in most cases, with a mortality rate of only 2%. Conclusions: cvPRES is most often associated with higher blood pressure compared to prior studies with typical PRES. The pons is most often involved. Despite the severity of blood pressure and critical brain stem involvement, those with cvPRES have favorable functional outcomes and a lower mortality rate than typical PRES, likely attributable to reversible vasogenic edema without significant neuronal dysfunction. Full article

The presence of dichotomizing neurons in the dorsal root ganglia (DRG) of cattle, innervating both the reticulum and the withers, may indicate a pre-spinal convergence of visceral and cutaneous sensory information, i.e., that the DRG primary sensory neurons may elaborate the sensory information coming from two different anatomical areas before reaching the secondary sensory neurons within the spinal cord. This anatomical feature could be the underlying basis for the cutaneous allodynia observed in traumatic reticuloperitonitis, also known as the “Kalchschmidt pain test”. The aim of the study was to identify the DRG primary sensory neurons innervating the reticulum and the withers by using two different retrograde fluorescent tracers, Fast Blue (FB, affinity for cytoplasm) and Diamidino Yellow (DY, affinity for nucleus). In two anesthetized calves, FB and DY were injected into the reticulum and skin of the withers, respectively. At the end of the experimental period, the calves were deeply anesthetized and then euthanatized. The thoracic (T1–T8) DRG were collected and processed to obtain cryosections which were examined on a fluorescent microscope. A large number of neurons localized, especially in the T7 DRG, presented nuclei labeled with DY. On the contrary, only a few neurons localized exclusively in T6 and T7 DRG presented the cytoplasm labeled with FB. No neurons displayed FB and DY simultaneously within the cytoplasm and nucleus, respectively. The absence of double-labeled DRG neurons suggests that the convergence of visceral and somatic sensory inputs underlying the Kalchschmidt pain response likely does not occur at the level of individual DRG neurons. Rather, it may involve higher-order integrative centers, possibly including vagal pathways and brainstem nuclei which integrate the afferent information to coordinate respiratory movements of the diaphragm, intercostal muscles, and larynx. Although limited by the sample size, this case study provides a neuroanatomical basis for further investigation into central mechanisms of referred visceral pain in cattle. Full article

Human genome studies have suggested that strawberry notch homologue 1 (SBNO1) is crucial for normal brain development, with mutations potentially contributing to neurodevelopmental disorders. In a previous study, we observed significant developmental abnormalities in the neocortex of Sbno1 as early as one week after birth. In the present study, we conducted an extensive analysis of Sbno1 postnatal expression in the brain of C57BL/6 mice using a newly developed in-house polyclonal antibody against Sbno1. We found that Sbno1 is expressed in all neurons, with certain neuronal populations exhibiting distinct dynamic changes (both temporal and spatial) in expression level. These findings suggest that the neuronal expression of Sbno1 is developmentally regulated after birth. They also indicate that while Sbno1 may play a general role across all neurons, it may also serve more specialized functions in certain neuronal types and/or for certain cellular activities related to particular neuronal pathways. Full article

The ultrastructural organization of the nuclei of the tegmental region in juvenile chum salmon (Oncorhynchus keta) was examined using transmission electron microscopy (TEM). The dorsal tegmental nuclei (DTN), the nucleus of fasciculus longitudinalis medialis (NFLM), and the nucleus of the oculomotor nerve (NIII) were studied. The ultrastructural examination provided detailed ultrastructural characteristics of neurons forming the tegmental nuclei and showed neuro–glial relationships in them. Neurons of three size types with a high metabolic rate, characterized by the presence of numerous mitochondria, polyribosomes, Golgi apparatus, and cytoplasmic inclusions (vacuoles, lipid droplets, and dense bodies), were distinguished. It was found that large interneurons of the NFLM formed contacts with protoplasmic astrocytes. Excitatory synaptic structures were identified in the tegmentum and their detailed characteristic are provided for the first time. Microglia-like cells were found in the NIII. The ultrastructural characteristics of neurogenic zones of the tegmentum of juvenile chum salmon were also determined for the first time. In the neurogenic zones of the tegmentum, adult-type neural stem progenitor cells (aNSPCs) corresponding to cells of types III and IVa Danio rerio. In the neurogenic zones of the tegmentum, neuroepithelial-like cells (NECs) corresponding to cells previously described from the zebrafish cerebellum were found and characterized. In the tegmentum of juvenile chum salmon, patterns of paracrine neurosecretion were observed and their ultrastructural characteristics were recorded. Patterns of apoptosis in large neurons of the tegmentum were examined by TEM. Using immunohistochemical (IHC) labeling of the brain lipid-binding protein (BLBP) and aromatase B (AroB), patterns of their expression in the tegmentum of intact animals and in the post-traumatic period after acute injury to the medulla oblongata were characterized. The response to brainstem injury in chum salmon was found to activate multiple signaling pathways, which significantly increases the BLBP and AroB expression in various regions of the tegmentum and valvula cerebelli. However, post-traumatic patterns of BLBP and AroB localizations are not the same. In addition to a general increase in BLBP expression in the tegmental parenchyma, BLBP overexpression was observed in the rostro-lateral tegmental neurogenic zone (RLTNZ), while AroB expression in the RLTNZ was completely absent. Another difference was the peripheral overexpression of AroB and the formation of dense reactive clusters in the ventro-medial zone of the tegmentum. Thus, in the post-traumatic period, various pathways were activated whose components were putative candidates for inducers of the “astrocyte-like” response in the juvenile chum salmon brain that are similar to those present in the mammalian brain. In this case, BLBP acted as a factor enhancing the differentiation of both radial glia and neurons. Estradiol from AroB+ astrocytes exerted paracrine neuroprotective effects through the potential inhibition of inflammatory processes. These results indicate a new role for neuronal aromatization as a mechanism preventing the development of neuroinflammation. Moreover, our findings support the hypothesis that BLBP is a factor enhancing neuronal and glial differentiation in the post-traumatic period in the chum salmon brain. Full article

Background and Clinical Significance: Aceruloplasminemia (ACP), a member of the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders, is a rare disorder caused by mutations in the ceruloplasmin (CP) gene. Iron accumulation in various organs, including the brain, liver, eyes, and heart, can lead to a broad clinical spectrum. Here, we report the first case of ACP in Greece. Case Presentation: Our patient was a 53-year-old male who was referred to our movement disorders center for a 6-month history of mild, unspecific, episodic dizziness and postural instability, and attention and memory deficits. Brain MRI revealed significant iron accumulation in multiple brain regions, including the dentate nuclei, cerebellar cortex, basal ganglia, thalamus, brainstem nuclei, and hypothalamus. These findings were particularly evident in susceptibility-weighted images. Fundoscopy revealed a normal retina, optic nerve, and macula. Whole-exome sequencing revealed a novel homozygous frameshift mutation in the CP gene [NM_000096.3:p.Thr3232fs (c.9695delC)]. This mutation has not been previously reported and is predicted to result in premature protein termination, supporting its pathogenic nature. Laboratory tests showed no anemia but revealed significantly elevated serum ferritin and low serum iron. Subsequent testing revealed extremely low serum CP and low serum copper. Despite less involvement of the myocardium, our patient succumbed to cardiac arrest. Conclusions: ACP should be considered in cases with minor neurological signs and symptoms. Brain MRI plays a significant role in early diagnosis. Close cardiac monitoring is also important. Full article

The dorsomedial hypothalamus nucleus (DMH) plays a pivotal role in the orchestration of sympathetic nervous system activities. Through its projections to the brainstem and pontomedullary nuclei, it controls heart rate, contractility, blood pressure, and respiratory activity, such as timing and volumes. The DMH integrates inputs from higher brain centers and processes these signals in order to modulate autonomic outflow accordingly. It has been demonstrated to be of particular significance in the context of stress responses, where it orchestrates the physiological adaptations that are necessary for all adaptative responses. The perifornical region (PeF), which is closely associated with the DMH, also makes a contribution to autonomic regulation. The involvement of the PeF region in autonomic control is evidenced by its function in coordinating the autonomic and endocrine responses to stress, frequently in conjunction with the DMH. The DMH and the PeF do not function in an isolated manner; rather, they are components of a comprehensive hypothalamic network that integrates several autonomic responses. This neural network could serve as a target for developing therapeutic strategies in cardiovascular diseases. Full article

The trigeminal sensory system consists of the trigeminal nerve, the trigeminal ganglion, and the trigeminal sensory nuclei (the mesencephalic nucleus, the principal nucleus, the spinal trigeminal nucleus, and several smaller nuclei). Various sensory signals carried by the trigeminal nerve from the orofacial area travel into the trigeminal sensory system, where they are processed into integrated sensory information that is relayed to higher sensory brain areas. Thus, knowledge of the trigeminal sensory system is essential for comprehending orofacial pain. This review elucidates the individual nuclei that comprise the trigeminal sensory system and their synaptic transmission. Additionally, it discusses four types of orofacial pain and their relationship to the system. Consequently, this review aims to enhance the understanding of the mechanisms underlying orofacial pain. Full article

The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular’s connections to the limbic system might play a role in the aversive and emotional component of pain, its connections to the descending pain system might be involved in pain intensity coding. Here, we used anterograde tracing with viral expression of mCherry fluorescent protein, to examine the connectivity of insular axons to different brainstem nuclei involved in the descending modulation of pain in detail. We found extensive connections to the main areas of descending pain control, namely, the periaqueductal gray (PAG) and the raphe magnus (RMg). In addition, we also identified an extensive insular connection to the parabrachial nucleus (PBN). Although not as extensive, we found a consistent axonal input from the insula to different noradrenergic nuclei, the locus coeruleus (LC), the subcoereuleus (SubCD) and the A5 nucleus. These connections emphasize a prominent relation of the insula with the descending pain modulatory system, which reveals an important role of the insula in pain processing through descending pathways. Full article

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain locations encompassing the hypothalamus and the brainstem, where the receptor controls several body functions, including metabolism. In a well-defined pathway to decrease appetite, hypothalamic proopiomelanocortin (POMC) neurons localized in the arcuate nucleus (Arc) project to MC4R neurons in the paraventricular nuclei (PVN) to release the natural MC4R agonist α-melanocyte-stimulating hormone (α-MSH). Arc neurons also project excitatory glutamatergic fibers to the MC4R neurons in the PVN for a fast synaptic transmission to regulate a satiety pathway potentiated by α-MSH. By using super-resolution microscopy, we found that in hypothalamic neurons in a primary culture, postsynaptic density protein 95 (PSD95) colocalizes with GluN1, a subunit of the ionotropic N-methyl-D-aspartate receptor (NMDAR). Thus, hypothalamic neurons form excitatory postsynaptic specializations. To study the MC4R distribution at these sites, tagged HA-MC4R under the synapsin promoter was expressed in neurons by adeno-associated virus (AAV) gene transduction. HA-MC4R immunofluorescence peaked at the center and in proximity to the PSD95- and NMDAR-expressing sites. These data provide morphological evidence that MC4R localizes together with glutamate receptors at postsynaptic and peri-postsynaptic sites. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with no effective treatments, not least due to the lack of authentic animal models. Typically, rodent models recapitulate the effects but not causes of AD, such as cholinergic neuron loss: lesioning of cholinergic neurons mimics the cognitive decline reminiscent of AD but not its neuropathology. Alternative models rely on the overexpression of genes associated with familial AD, such as amyloid precursor protein, or have genetically amplified expression of mutant tau. Yet transgenic rodent models poorly replicate the neuropathogenesis and protein overexpression patterns of sporadic AD. Seeding rodents with amyloid or tau facilitates the formation of these pathologies but cannot account for their initial accumulation. Intracerebral infusion of proinflammatory agents offer an alternative model, but these fail to replicate the cause of AD. A novel model is therefore needed, perhaps similar to those used for Parkinson’s disease, namely adult wildtype rodents with neuron-specific (dopaminergic) lesions within the same vulnerable brainstem nuclei, ‘the isodendritic core’, which are the first to degenerate in AD. Site-selective targeting of these nuclei in adult rodents may recapitulate the initial neurodegenerative processes in AD to faithfully mimic its pathogenesis and progression, ultimately leading to presymptomatic biomarkers and preventative therapies. Full article

The central nervous system of Pacific salmon retains signs of embryonic structure throughout life and a large number of neuroepithelial neural stem cells (NSCs) in the proliferative areas of the brain, in particular. However, the adult nervous system and neurogenesis studies on rainbow trout, Oncorhynchus mykiss, are limited. Here, we studied the localization of glutamine synthetase (GS), vimentin (Vim), and nestin (Nes), as well as the neurons formed in the postembryonic period, labeled with doublecortin (DC), under conditions of homeostatic growth in adult cerebellum and brainstem of Oncorhynchus mykiss using immunohistochemical methods and Western Immunoblotting. We observed that the distribution of vimentin (Vim), nestin (Nes), and glutamine synthetase (GS), which are found in the aNSPCs of both embryonic types (neuroepithelial cells) and in the adult type (radial glia) in the cerebellum and the brainstem of trout, has certain features. Populations of the adult neural stem/progenitor cells (aNSPCs) expressing GS, Vim, and Nes have different morphologies, localizations, and patterns of cluster formation in the trout cerebellum and brainstem, which indicates the morphological and, obviously, functional heterogeneity of these cells. Immunolabeling of PCNA revealed areas in the cerebellum and brainstem of rainbow trout containing proliferating cells which coincide with areas expressing Vim, Nes, and GS. Double immunolabeling revealed the PCNA/GS PCNA/Vim coexpression patterns in the neuroepithelial-type cells in the PVZ of the brainstem. PCNA/GS coexpression in the RG was detected in the submarginal zone of the brainstem. The results of immunohistochemical study of the DC distribution in the cerebellum and brainstem of trout have showed a high level of expression of this marker in various cell populations. This may indicate: (i) high production of the adult-born neurons in the cerebellum and brainstem of adult trout, (ii) high plasticity of neurons in the cerebellum and brainstem of trout. We assume that the source of new cells in the trout brain, along with PVZ and SMZ, containing proliferating cells, may be local neurogenic niches containing the PCNA-positive and silent (PCNA-negative), but expressing NSC markers, cells. The identification of cells expressing DC, Vim, and Nes in the IX-X cranial nerve nuclei of trout was carried out. Full article

The sensorimotor gating is a nervous system function that modulates the acoustic startle response (ASR). Prepulse inhibition (PPI) phenomenon is an operational measure of sensorimotor gating, defined as the reduction of ASR when a high intensity sound (pulse) is preceded in milliseconds by a weaker stimulus (prepulse). Brainstem nuclei are associated with the mediation of ASR and PPI, whereas cortical and subcortical regions are associated with their modulation. However, it is still unclear how the modulatory units can influence PPI. In the present work, we developed a computational model of a neural circuit involved in the mediation (brainstem units) and modulation (cortical and subcortical units) of ASR and PPI. The activities of all units were modeled by the leaky-integrator formalism for neural population. The model reproduces basic features of PPI observed in experiments, such as the effects of changes in interstimulus interval, prepulse intensity, and habituation of ASR. The simulation of GABAergic and dopaminergic drugs impaired PPI by their effects over subcortical units activity. The results show that subcortical units constitute a central hub for PPI modulation. The presented computational model offers a valuable tool to investigate the neurobiology associated with disorder-related impairments in PPI. Full article

Fibromyalgia syndrome (FM) is a chronic pain condition that affects a significant portion of the population; yet, this condition is still poorly understood. Prior research has suggested that individuals with FM display a heightened sensitivity to pain and signs of autonomic dysfunction. Recent advances in functional MRI analysis methods to model blood-oxygenation-level-dependent (BOLD) responses across networks of regions, and structural and physiological modeling (SAPM) have shown the potential to provide more detailed information about altered neural activity than was previously possible. Therefore, this study aimed to apply novel analysis methods to investigate altered neural processes underlying pain sensitivity in FM in functional magnetic resonance imaging (fMRI) data from the brainstem and spinal cord. Prior fMRI studies have shown evidence of functional differences in fibromyalgia (FM) within brain regions associated with pain’s motivational aspects, as well as differences in neural activity related to pain regulation, arousal, and autonomic homeostatic regulation within the brainstem and spinal cord regions. We, therefore, hypothesized that nociceptive processing is altered in FM compared to healthy controls (HCs) in the brainstem and spinal cord areas linked to autonomic function and descending pain regulation, including the parabrachial nuclei (PBN) and nucleus tractus solitarius (NTS). We expected that new details of this altered neural signaling would be revealed with SAPM. The results provide new evidence of altered neural signaling in FM related to arousal and autonomic homeostatic regulation. This further advances our understanding of the altered neural processing that occurs in women with FM. Full article

In contrast to cats and dogs, here we report that the α₂-adrenergic receptor antagonist yohimbine is emetic and corresponding agonists clonidine and dexmedetomidine behave as antiemetics in the least shrew model of vomiting. Yohimbine (0, 0.5, 0.75, 1, 1.5, 2, and 3 mg/kg, i.p.) caused vomiting in shrews in a bell-shaped and dose-dependent manner, with a maximum frequency (0.85 ± 0.22) at 1 mg/kg, which was accompanied by a key central contribution as indicated by increased expression of c-fos, serotonin and substance P release in the shrew brainstem emetic nuclei. Our comparative study in shrews demonstrates that clonidine (0, 0.1, 1, 5, and 10 mg/kg, i.p.) and dexmedetomidine (0, 0.01, 0.05, and 0.1 mg/kg, i.p.) not only suppress yohimbine (1 mg/kg, i.p.)-evoked vomiting in a dose-dependent manner, but also display broad-spectrum antiemetic effects against diverse well-known emetogens, including 2-Methyl-5-HT, GR73632, McN-A-343, quinpirole, FPL64176, SR141716A, thapsigargin, rolipram, and ZD7288. The antiemetic inhibitory ID₅₀ values of dexmedetomidine against the evoked emetogens are much lower than those of clonidine. At its antiemetic doses, clonidine decreased shrews’ locomotor activity parameters (distance moved and rearing), whereas dexmedetomidine did not do so. The results suggest that dexmedetomidine represents a better candidate for antiemetic potential with advantages over clonidine. Full article