Hypothalamic-amygdalar-brainstem volume reduction in a patient with narcolepsy secondary to diffuse axonal injury.
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ABSTRACT:
SUBMITTER: Yassin W
PROVIDER: S-EPMC4410933 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Study objectivesNarcolepsy type 1 (NT1) is a neurological sleep disorder. Postmortem studies have shown 75%-90% loss of the 50 000-70 000 hypocretin-producing neurons and 64%-94% increase in the 64 000-120 000 histaminergic neurons and conflicting indications of gliosis in the hypothalamus of NT1 patients. The aim of this study was to compare MRI-based volumes of the hypothalamus in patients with NT1 and controls in vivo.MethodsWe used a segmentation tool based on deep learning included in Freesurfer and computed the volume of the whole hypothalamus, left/right part of the hypothalamus, and 10 hypothalamic subregions. We included 54 patients with post-H1N1 NT1 (39 females, mean age 21.8 ± 11.0 years) and 114 controls (77 females, mean age 23.2 ± 9.0 years). Group differences were tested with general linear models using permutation testing in Permutation Analysis of Linear Models and evaluated after 10 000 permutations, yielding two-tailed P-values. Furthermore, a stepwise Bonferroni correction was performed after dividing hypothalamus into smaller regions.ResultsThe analysis revealed larger volume for patients compared to controls for the whole hypothalamus (Cohen's d = 0.71, p = 0.0028) and for the left (d = 0.70, p = 0.0037) and right part of the hypothalamus (d = 0.65, p = 0.0075) and left (d = 0.72, p = 0.0036) and right tubular-inferior (d = 0.71, p = 0.0037) hypothalamic subregions.ConclusionsIn conclusion, patients with post-H1N1 NT1 showed significantly larger hypothalamic volume than controls, in particular in the tubular-inferior subregions which could reflect several processes as previous studies have indicated neuroinflammation, gliosis, and changes in the numbers of different cell types.
| S-EPMC10636249 | biostudies-literature
Project description:The paraventricular hypothalamic nucleus (PVH) contains many neurons that innervate the brainstem, but information regarding their target sites remains incomplete. Here we labeled neurons in the rat PVH with an anterograde axonal tracer, Phaseolus vulgaris leucoagglutinin (PHAL), and studied their descending projections in reference to specific neuronal subpopulations throughout the brainstem. While many of their target sites were identified previously, numerous new observations were made. Major findings include: 1) In the midbrain, the PVH projects lightly to the ventral tegmental area, Edinger-Westphal nucleus, ventrolateral periaqueductal gray matter, reticular formation, pedunculopontine tegmental nucleus, and dorsal raphe nucleus. 2) In the dorsal pons, the PVH projects heavily to the pre-locus coeruleus, yet very little to the catecholamine neurons in the locus coeruleus, and selectively targets the viscerosensory subregions of the parabrachial nucleus. 3) In the ventral medulla, the superior salivatory nucleus, retrotrapezoid nucleus, compact and external formations of the nucleus ambiguous, A1 and caudal C1 catecholamine neurons, and caudal pressor area receive dense axonal projections, generally exceeding the PVH projection to the rostral C1 region. 4) The medial nucleus of the solitary tract (including A2 noradrenergic and aldosterone-sensitive neurons) receives the most extensive projections of the PVH, substantially more than the dorsal vagal nucleus or area postrema. Our findings suggest that the PVH may modulate a range of homeostatic functions, including cerebral and ocular blood flow, corneal and nasal hydration, ingestive behavior, sodium intake, and glucose metabolism, as well as cardiovascular, gastrointestinal, and respiratory activities.
| S-EPMC2868510 | biostudies-literature
Project description:Increasing evidence suggests that secondary injury after diffuse axonal injury (DAI) damages more axons than the initial insult, but the underlying mechanisms of this phenomenon are not fully understood. Recent studies show that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and have been shown to be associated with brain damage. The purpose of this study was to investigate the role of the TLR4 signalling pathway in secondary axonal injury in the cortices of DAI rats. TLR4 was mainly localized in microglial cells and neurons, and the levels of TLR4 downstream signalling molecules, including TLR4, myeloid differentiation primary response gene 88, toll/IR-1-(TIR-) domain-containing adaptor protein inducing interferon-beta, interferon regulatory factor 3, interferon β, nuclear factor κB (NF-κB) p65, and phospho-NF-κB p65, significantly increased and peaked at 1 d after DAI. Inhibition of TLR4 by TAK-242 attenuated apoptosis, neuronal and axonal injury, and glial responses. The neuroprotective effects of TLR4 inhibition were associated with decreases in the levels of TLR4 downstream signalling molecules and inflammatory factors, including interleukin-1β, interleukin-6, and tumour necrosis factor-α. These results suggest that the TLR4 signalling pathway plays an important role in secondary injury and may be an important therapeutic target following DAI.
| S-EPMC4961816 | biostudies-literature
Project description:In this study, three problems associated with diagnosing diffuse axonal injury (DAI) in patients with traumatic brain injury are reviewed: the shortage of scientific evidence supporting the 6-hour loss of consciousness (LOC) diagnostic criterion to discriminate concussion and DAI, the low sensitivity of conventional brain MRI in the detection of DAI lesions, and the inappropriateness of the term diffuse in DAI. Pathological study by brain biopsy is required to confirm DAI; however, performing a brain biopsy for the diagnosis of DAI in a living patient is impossible. Therefore, the diagnosis of DAI in a living patient is clinically determined based on the duration of LOC, clinical manifestations, and the results of conventional brain MRI. There is a shortage of scientific evidence supporting the use of the 6-hour LOC criterion to distinguish DAI from concussion, and axonal injuries have been detected in many concussion cases with a less than 6-hour LOC. Moreover, due to the low sensitivity of conventional brain MRI, which can only detect DAI lesions in approximately half of DAI patients, diagnostic MRI criteria for DAI are not well established. In contrast, diffusion tensor imaging (DTI) has been shown to have high sensitivity for the detection of DAI lesions. As DTI is a relatively new method, further studies aimed at the establishment of diagnostic criteria for DAI detection using DTI are needed. On the other hand, because DAI distribution is not diffuse but multifocal, and because axonal injury lesions have been detected in concussion patients, steps to standardize the use of terms related to axonal injury in both concussion and DAI are necessary.
| S-EPMC7168326 | biostudies-literature
Project description:Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope® to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.
| S-EPMC7225974 | biostudies-literature
Project description:ObjectiveThe aims of this study were to investigate changes in regional brain volume after concussion (mild traumatic brain injury) and to examine the relationship between change in brain volume and cognitive deficits.DesignTwenty-eight patients with mild traumatic brain injury and 27 age-matched controls were included in this study. Magnetic resonance imaging (3 T) data were obtained from the participants. Structural brain volume changes were examined using tensor-based morphometry, which identifies regional structural differences in the whole brain, including cerebrospinal fluid, gray matter, and white matter. Volume contraction and expansion were compared between groups using a two-sample t test. The association between time post-injury or neurocognitive function and volumetric changes was examined using regression analysis.ResultsIndividuals with mild traumatic brain injury exhibited volume reduction in the brainstem, including the pontine reticular formation. Regional cerebral volume changes were not associated with time post-injury but were significantly associated with neurocognitive function, especially with executive card sorting test, forward digit span test, and performance on verbal learning test. The greater regional cerebral volume was associated with better cognitive performance after mild traumatic brain injury.ConclusionDecreased brainstem volume may indicate its vulnerability to traumatic injury, and cerebral volume in specific regions was positively associated with patients' cognitive function after injury.
| S-EPMC8032213 | biostudies-literature
Project description: Not available
| S-EPMC6461146 | biostudies-literature
Project description:ObjectiveDiffuse axonal injury (DAI) is a specific type of traumatic brain injury caused by shearing forces leading to widespread tearing of axons and small vessels. Traumatic microbleeds (TMBs) are regarded as a radiological marker for DAI. This study aims to compare DAI-associated TMBs at 3 Tesla (T) and 7 T susceptibility weighted imaging (SWI) to evaluate possible diagnostic benefits of ultra-high field (UHF) MRI.Material and methods10 study participants (4 male, 6 female, age range 20-74 years) with known DAI were included. All MR exams were performed with a 3 T MR system (Magnetom Skyra) and a 7 T MR research system (Magnetom 7 T, Siemens AG, Healthcare Sector, Erlangen, Germany) each in combination with a 32-channel-receive coil. The average time interval between trauma and imaging was 22 months. Location and count of TMBs were independently evaluated by two neuroradiologists on 3 T and 7 T SWI images with similar and additionally increased spatial resolution at 7 T. Inter- and intraobserver reliability was assessed using the interclass correlation coefficient (ICC). Count and diameter of TMB were evaluated with Wilcoxon signed rank test.ResultsSusceptibility weighted imaging revealed a total of 485 TMBs (range 1-190, median 25) at 3 T, 584 TMBs (plus 20%, range 1-262, median 30.5) at 7 T with similar spatial resolution, and 684 TMBs (plus 41%, range 1-288, median 39.5) at 7 T with 10-times higher spatial resolution. Hemorrhagic DAI appeared significantly larger at 7 T compared to 3 T (p = 0.005). Inter- and intraobserver correlation regarding the counted TMB was high and almost equal 3 T and 7 T.Conclusion7 T SWI improves the depiction of small hemorrhagic DAI compared to 3 T and may be supplementary to lower field strengths for diagnostic in inconclusive or medicolegal cases.
| S-EPMC4368671 | biostudies-literature
Project description:Over the past decade, investigators have attempted to establish the pathophysiological mechanisms by which non-penetrating injuries damage the brain. Several studies have implicated either membrane poration or ion channel dysfunction pursuant to neuronal cell death as the primary mechanism of injury. We hypothesized that traumatic stimulation of integrins may be an important etiological contributor to mild Traumatic Brain Injury. In order to study the effects of forces at the cellular level, we utilized two hierarchical, in vitro systems to mimic traumatic injury to rat cortical neurons: a high velocity stretcher and a magnetic tweezer system. In one system, we controlled focal adhesion formation in neurons cultured on a stretchable substrate loaded with an abrupt, one dimensional strain. With the second system, we used magnetic tweezers to directly simulate the abrupt injury forces endured by a focal adhesion on the neurite. Both systems revealed variations in the rate and nature of neuronal injury as a function of focal adhesion density and direct integrin stimulation without membrane poration. Pharmacological inhibition of calpains did not mitigate the injury yet the inhibition of Rho-kinase immediately after injury reduced axonal injury. These data suggest that integrin-mediated activation of Rho may be a contributor to the diffuse axonal injury reported in mild Traumatic Brain Injury.
| S-EPMC3142195 | biostudies-literature
Project description:There is much controversy about the potential impact of spinal cord injury (SCI) on brain anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ), we performed statistical analyses on grey and white matter volumes as well as on parameter maps indicative for myelin, iron, and free tissue water content in the brain of complete SCI patients (n = 14) and healthy individuals (n = 14). Our regionally unbiased white matter analysis showed a significant volume reduction of the dorsal aspect at the junction between the most rostral part of the spinal cord and the medulla oblongata consistent with Wallerian degeneration of proprioceptive axons in the dorsal column tracts in SCI subjects. This observation strongly correlated with spinal cord atrophy assessed by quantification of the spinal cord cross-sectional area at the cervical level C2/3. These findings suggest that Wallerian degeneration of the dorsal column tracts represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in other brain regions representing remote changes in the course of chronic SCI could neither be confirmed by conventional VBM nor by VBQ analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.
| S-EPMC8217673 | biostudies-literature