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Emotional dysregulation following a concussion is well established. New onset of major psychiatric diseases such as bipolar disorder (BPD) post-concussion has not been investigated. BPD typically presents with an initial depressive episode followed by mania and concurrent depressive and manic states. Multiple theories explaining the etiology of BPD exist, including the diathesis-stress model (DiSM), though an accepted theory is not established. In this case study, medical records of a 50-year-old ambidextrous male with co-morbid attention deficit hyperactivity disorder (ADHD) inattentive type, obsessive-compulsive disorder (OCD), and a family history of BPD suffered a motor vehicle collision (MVC) resulting in a grade II concussion. New onset BPD was diagnosed one-year after a concussion following an involuntary admission and led to the patient self-terminating his medications and suffering a hypertensive crisis and aortic dissection, and stroke. One year later, the patient was again involuntarily admitted for a suicide attempt. Bipolar disorder persisted unchanged indefinitely. This case study may serve as a real-world example of the DiSM in the etiology of BPD post-concussion. We aim to highlight the importance of early identification of risk factors for progression to psychiatric conditions following concussion.
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Primary head injury is often followed by secondary brain damage. However, the association between injury circumstances and the prevalence of secondary injuries remains unclear. We report the prevalence and association of secondary brain injuries with the circumstances in which a head injury was sustained. The sample comprised 76 neuropathologically examined medico-legal autopsy cases with an acute primary head injury. Neuropathology reports were analysed to determine the prevalence of various secondary injuries, i.e., hypoxic-ischaemic neuronal injury, brain oedema, and vascular axonal injury (VAI). The prevalences were compared between cases from three distinct injury circumstances, i.e., fall, assault, and strangulation. The sample had a median age of 49 years (interquartile range 27-73) and 71.1% were identified as male. As for distinct injury circumstances, the sample comprised 14 fall cases, 21 assault victims, and 6 strangulation victims. The prevalence of hypoxic-ischaemic neuronal injury was highest in strangulations (100.0%), followed by assaults (81.0%) and falls (64.3%); of specific brain regions, statistically significant differences between the three case groups were found in frontal and parietal cortex (p ≤ 0.018) and the hippocampus (p = 0.005). Brain oedema was present in approximately half of assault (47.6%) and strangulation cases (50.0%), contrastingly to the lower prevalence in falls (7.1%; p = 0.024). The prevalence of VAI appeared higher among assault (23.8%) and strangulation cases (16.7%) compared to falls (7.1%), but the differences were not statistically significant. We conclude that hypoxic-ischaemic neuronal injury and brain oedema were more prevalent among assault and strangulation cases compared to falls.
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Traumatic brain injury (TBI) affects millions globally, with a majority of TBI cases being classified as mild, in which diffuse pathologies prevail. Two of the pathological hallmarks of TBI are diffuse axonal injury and microglial activation. While progress has been made investigating the breadth of TBI-induced axonal injury and microglial changes in rodents, the neuroinflammatory progression and interaction between microglia and injured axons following brain injury in humans is less well understood. Our group previously investigated microglial process convergence (MPC), in which processes of non-phagocytic microglia directly contact injured proximal axonal segments, in rats and micropigs acutely following TBI. These studies demonstrated that MPC occurred on injured axons in the micropig, but not in the rat, following diffuse TBI. While it has been shown that microglia co-exist and interact with injured axons in humans post-TBI, the occurrence of MPC has not been quantitatively measured in the human brain. Therefore, in the current study we sought to validate our pig findings in human postmortem tissue. We investigated MPC onto injured axonal swellings and intact myelinated fibers in cases from individuals that sustained a TBI and control human brain tissue using multiplex immunofluorescent histochemistry. We found an increase in MPC onto injured axonal swellings, consistent with our previous findings in micropigs, indicating that MPC is a clinically relevant phenomenon that warrants further investigation.
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INTRODUCTION: Motor neurons differ from sensory neurons in aspects including origins and surrounding environment. Understanding the similarities and differences in molecular response to peripheral nerve injury (PNI) and regeneration between sensory and motor neurons is crucial for developing effective drug targets for CNS regeneration. However, genome-wide comparisons of molecular changes between sensory and motor neurons following PNI remains limited. OBJECTIVES: This study aims to investigate genome-wide convergence and divergence of injury response between sensory and motor neurons to identify novel drug targets for neural repair. METHODS: We analyzed two large-scale RNA-seq datasets of in situ captured sensory neurons (SNs) and motoneurons (MNs) upon PNI, retinal ganglion cells and spinal cord upon CNS injury. Additionally, we integrated these with other related single-cell level datasets. Bootstrap DESeq2 and WGCNA were used to detect and explore co-expression modules of differentially expressed genes (DEGs). RESULTS: We found that SNs and MNs exhibited similar injury states, but with a delayed response in MNs. We identified a conserved regeneration-associated module (cRAM) with 274 shared DEGs. Of which, 47% of DEGs could be changed in injured neurons supported by single-cell resolution datasets. We also identified some less-studied candidates in cRAM, including genes associated with transcription, ubiquitination (Rnf122), and neuron-immune cells cross-talk. Further in vitro experiments confirmed a novel role of Rnf122 in axon growth. Analysis of the top 10% of DEGs with a large divergence suggested that both extrinsic (e.g., immune microenvironment) and intrinsic factors (e.g., development) contributed to expression divergence between SNs and MNs following injury. CONCLUSIONS: This comprehensive analysis revealed convergent and divergent injury response genes in SNs and MNs, providing new insights into transcriptional reprogramming of sensory and motor neurons responding to axonal injury and subsequent regeneration. It also identified some novel regeneration-associated candidates that may facilitate the development of strategies for axon regeneration.
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Traumatic brain injury (TBI) results from physical or traumatic injuries to the brain's surrounding bony structures and associated tissues, which can lead to various sequelae, including simple concussion, acute epidural hematoma, parenchymal contusions, subarachnoid hemorrhage, diffuse axonal injury, and chronic traumatic encephalopathy. Susceptibility-weighted imaging (SWI) has enhanced the accuracy of neuroimaging for these injuries. SWI is based on 3D gradient echo magnetic resonance imaging (MRI) with long echo times and flow compensation. Owing to its sensitivity to deoxyhemoglobin, hemosiderin, iron, and calcium, SWI is extremely informative and superior to conventional MRI for the diagnosis and follow-up of patients with acute, subacute, and prolonged hemorrhage. This systematic review aimed to evaluate and summarize the published articles that report SWI results for the evaluation of TBI and to determine correlations between clinical status and SWI results. Consequently, our analysis also aimed to identify the appropriate MRI sequences to use in the assessment of patients with TBI. We searched the Medline and Embase online electronic databases for relevant papers published from 2012 onwards. We found that SWI had higher sensitivity than gradient echo MRI in detecting and characterizing microbleeds in TBIs and was able to differentiate diamagnetic calcifications from paramagnetic microhemorrhages. However, it is important that future research not only continues to evaluate the utility of SWI in TBIs but also attempts to overcome the limitations of the studies described in this review, which should help validate the conclusions and recommendations from our analysis.
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Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Diffuse axonal injury (DAI) following sudden acceleration and deceleration can lead to cognitive function decline. Various treatments have been proposed. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique, is a potential treatment for enhancing neuroplasticity in cases of brain injury. The therapeutic efficacy of rTMS on cognitive function remains unconfirmed. This study investigated the effects of rTMS and the underlying molecular biomechanisms using a rat model of DAI. Sprague-Dawley rats (n = 18) were randomly divided into two groups: one receiving rTMS after DAI and the other without brain stimulation. All rats were subjected to sudden acceleration and deceleration using a DAI modeling machine to induce damage. MRI was performed to confirm the DAI lesion. The experimental group received rTMS at a frequency of 1 Hz over the frontal cortex for 10 min daily for five days. To assess spatial memory, we conducted the Morris water maze (MWM) test one day post-brain damage and one day after the five-day intervention. A video tracking system recorded the escape latency. After post-MWM tests, all rats were euthanized, and their brain tissues, particularly from the hippocampus, were collected for immunohistochemistry and western blot analyses. The escape latency showed no difference on the MWM test after DAI, but a significant difference was observed after rTMS between the two groups. Immunohistochemistry and western blot analyses indicated increased expression of BDNF, VEGF, and MAP2 in the hippocampal brain tissue of the DAI-T group. In conclusion, rTMS improved cognitive function in the DAI rat model. The increased expression of BDNF, VEGF, and MAP2 in the DAI-T group supports the potential use of rTMS in treating cognitive impairments associated with DAI.
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Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, we explore these pathogenic mechanisms utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice. We observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus) after r-mTBI. This elevation was accompanied by astrogliosis, microgliosis, and the accumulation of amyloid precursor protein (APP). Mice subjected to r-mTBI displayed impaired motor learning and spatial memory. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as pathological signatures of gliosis, oxidative stress, axonal damage, and white matter damage. These findings indicate NHE1 upregulation plays a role in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 may be a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.
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Traumatic brain injury (TBI) consists of an external physical force that causes brain function impairment or pathology and globally affects 50 million people each year, with a cost of 400 billion US dollars. Clinical presentation of TBI can occur in many forms, and patients usually require prolonged hospital care and lifelong rehabilitation, which leads to an impact on the quality of life. For this narrative review, no particular method was used to extract data. With the aid of health descriptors and Medical Subject Heading (MeSH) terms, a search was thoroughly conducted in databases such as PubMed and Google Scholar. After the application of exclusion and inclusion criteria, a total of 146 articles were effectively used for this review. Results indicate that rehabilitation after TBI happens through neuroplasticity, which combines neural regeneration and functional reorganization. The role of technology, including artificial intelligence, virtual reality, robotics, computer interface, and neuromodulation, is to impact rehabilitation and life quality improvement significantly. Pharmacological intervention, however, did not result in any benefit when compared to standard care and still needs further research. It is possible to conclude that, given the high and diverse degree of disability associated with TBI, rehabilitation interventions should be precocious and tailored according to the individual's needs in order to achieve the best possible results. An interdisciplinary patient-centered care health team and well-oriented family members should be involved in every stage. Lastly, strategies must be adequate, well-planned, and communicated to patients and caregivers to attain higher functional outcomes.
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BACKGROUND: Although cadmium exposure had been demonstrated to be toxic to the nervous system, little was known about the link between cadmium exposure and axonal injury. Therefore, the present study aimed to reveal whether there was any correlation between blood cadmium and serum neurofilament light chain (NfL) levels in the general population. METHODS: This study included 1040 participants with a median (IQR) age of 47 (35-60) years from the 2013-2014 National Health and Nutrition Examination Survey. Serum NfL levels were measured through immunoassay, and whole blood cadmium concentrations were detected by means of inductively coupled plasma mass spectrometry. Linear regression and restricted cubic spline model was applied to analyze the significance of relationship between blood cadmium and serum NfL levels. RESULTS: In the full adjusted model, blood cadmium levels were found to be positively associated with serum NfL levels (Q4 vs Q1, ß = 3.35, 95â¯%CI: 0.41, 6.30, p for trend = 0.014). A potential linear positive dose-effect relationship was discovered between blood cadmium and serum NfL levels (p for non-linearity = 0.15). According to the result of stratified analysis, the significant positive relationship between blood cadmium and serum NfL levels was present only in the population of middle-aged and older adults. CONCLUSION: The present study suggested a positive association between blood cadmium and serum NfL levels in the general US population.
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Cádmio , Exposição Ambiental , Proteínas de Neurofilamentos , Inquéritos Nutricionais , Humanos , Cádmio/sangue , Pessoa de Meia-Idade , Adulto , Feminino , Proteínas de Neurofilamentos/sangue , Masculino , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , IdosoRESUMO
Axons successfully repaired with polyethylene glycol (PEG) fusion tecnology restored axonal continuity thereby preventing their Wallerian degeneration and minimizing muscle atrophy. PEG fusion studies in animal models and preliminary clinical trials involving patients with digital nerve repair have shown promise for this therapeutic approach. PEG fusion is safe to perform, and given the enormous potential benefits, there is no reason not to explore its therapeutic potential.
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Traumatismos dos Nervos Periféricos , Polietilenoglicóis , Humanos , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/administração & dosagem , Traumatismos dos Nervos Periféricos/cirurgia , Animais , Regeneração NervosaRESUMO
OBJECTIVES: We analysed magnetic resonance imaging (MRI) findings after traumatic brain injury (TBI) aiming to improve the grading of traumatic axonal injury (TAI) to better reflect the outcome. METHODS: Four-hundred sixty-three patients (8-70 years) with mild (n = 158), moderate (n = 129), or severe (n = 176) TBI and early MRI were prospectively included. TAI presence, numbers, and volumes at predefined locations were registered on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging, and presence and numbers on T2*GRE/SWI. Presence and volumes of contusions were registered on FLAIR. We assessed the outcome with the Glasgow Outcome Scale Extended. Multivariable logistic and elastic-net regression analyses were performed. RESULTS: The presence of TAI differed between mild (6%), moderate (70%), and severe TBI (95%). In severe TBI, bilateral TAI in mesencephalon or thalami and bilateral TAI in pons predicted worse outcomes and were defined as the worst grades (4 and 5, respectively) in the Trondheim TAI-MRI grading. The Trondheim TAI-MRI grading performed better than the standard TAI grading in severe TBI (pseudo-R2 0.19 vs. 0.16). In moderate-severe TBI, quantitative models including both FLAIR volume of TAI and contusions performed best (pseudo-R2 0.19-0.21). In patients with mild TBI or Glasgow Coma Scale (GCS) score 13, models with the volume of contusions performed best (pseudo-R2 0.25-0.26). CONCLUSIONS: We propose the Trondheim TAI-MRI grading (grades 1-5) with bilateral TAI in mesencephalon or thalami, and bilateral TAI in pons as the worst grades. The predictive value was highest for the quantitative models including FLAIR volume of TAI and contusions (GCS score <13) or FLAIR volume of contusions (GCS score ≥ 13), which emphasise artificial intelligence as a potentially important future tool. CLINICAL RELEVANCE STATEMENT: The Trondheim TAI-MRI grading reflects patient outcomes better in severe TBI than today's standard TAI grading and can be implemented after external validation. The prognostic importance of volumetric models is promising for future use of artificial intelligence technologies. KEY POINTS: Traumatic axonal injury (TAI) is an important injury type in all TBI severities. Studies demonstrating which MRI findings that can serve as future biomarkers are highly warranted. This study proposes the most optimal MRI models for predicting patient outcome at 6 months after TBI; one updated pragmatic model and a volumetric model. The Trondheim TAI-MRI grading, in severe TBI, reflects patient outcome better than today's standard grading of TAI and the prognostic importance of volumetric models in all severities of TBI is promising for future use of AI.
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In traumatic brain injury, white matter diffusion restriction can be an imaging manifestation of non-hemorrhagic axonal injury. In this article, a different pattern of widespread white matter diffusion restriction associated with ipsilateral cortical damage, all noted in pediatric and young adult TBI patients, is presented. Its atypical pattern of distribution and extensive scope on imaging suggest excitotoxicity and intramyelinic edema as possible underlying mechanisms.
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Head trauma (HT) in pediatric patients is the number one cause of mortality and morbidity in children. Although computer tomography (CT) imaging provides ample information in assessing acute traumatic brain injuries (TBIs), there are instances when magnetic resonance imaging (MRI) is needed. Due to its high sensitivity in diagnosing small bleeds, MRI offers a well-documented evaluation of primary acute TBIs. Our pictorial essay aims to present some of the latest imaging protocols employed in head trauma and review some practical considerations. Injury mechanisms in accidental HT, lesions' topography, and hematoma signal variability over time are also discussed. Acute primary intra- and extra-axial lesions and their MRI aspect are showcased using images from patients in our hospital. This pictorial essay has an educational purpose. It is intended to guide young emergency and intensive care unit doctors, neurologists, and neurosurgeons in diagnosing acute primary TBIs on MRI while waiting for the official radiologist's report. The presentation focuses on the most frequent traumatic lesions encountered in acute pediatric head trauma.
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Ubiquitin C-terminal hydrolase L1 (UCHL1) is a neuronal protein important in maintaining axonal integrity and motor function and may be important in the pathogenesis of many neurological disorders. UCHL1 may ameliorate acute injury and improve recovery after cerebral ischemia. In the current study, the hypothesis that UCHL1's hydrolase activity underlies its effect in maintaining axonal integrity and function is tested after ischemic injury. Hydrolase activity was inhibited by treatment with a UCHL1 hydrolase inhibitor or by employing knockin mice bearing a mutation in the hydrolase active site (C90A). Ischemic injury was induced by oxygen-glucose deprivation (OGD) in brain slice preparations and by transient middle cerebral artery occlusion (tMCAO) surgery in mice. Hydrolase activity inhibition increased restoration time and decreased the amplitude of evoked axonal responses in the corpus callosum after OGD. Mutation of the hydrolase active site exacerbated white matter injury as detected by SMI32 immunohistochemistry, and motor deficits as detected by beam balance and cylinder testing after tMCAO. These results demonstrate that UCHL1 hydrolase activity ameliorates white matter injury and functional deficits after acute ischemic injury and support the hypothesis that UCHL1 activity plays a significant role in preserving white matter integrity and recovery of function after cerebral ischemia.
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Identification of Traumatic axonal injury (TAI) is critical in clinical practice, particularly in terms of long-term prognosis, but also for medico-legal issues, to verify whether the death or the after-effects were attributable to trauma. Multidisciplinary approaches are an undeniable asset when it comes to solving these problems. The aim of this work is therefore to list the different techniques needed to identify axonal lesions and to understand the lesion mechanisms involved in their formation. Imaging can be used to assess the consequences of trauma, to identify indirect signs of TAI, to explain the patient's initial symptoms and even to assess the patient's prognosis. Three-dimensional reconstructions of the skull can highlight fractures suggestive of trauma. Microscopic and immunohistochemical techniques are currently considered as the most reliable tools for the early identification of TAI following trauma. Finite element models use mechanical equations to predict biomechanical parameters, such as tissue stresses and strains in the brain, when subjected to external forces, such as violent impacts to the head. These parameters, which are difficult to measure experimentally, are then used to predict the risk of injury. The integration of imaging data with finite element models allows researchers to create realistic and personalized computational models by incorporating actual geometry and properties obtained from imaging techniques. The personalization of these models makes their forensic approach particularly interesting.
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Lesão Axonal Difusa , Humanos , Fenômenos Biomecânicos , Lesão Axonal Difusa/diagnóstico por imagem , Lesão Axonal Difusa/fisiopatologia , Lesão Axonal Difusa/patologia , Análise de Elementos Finitos , Imageamento Tridimensional , Patologia Legal/métodos , Axônios/patologia , Axônios/fisiologia , Medicina Legal/métodosRESUMO
Given the extensive application of dexamethasone in both clinical settings and the livestock industry, human exposure to this drug can occur through various sources and pathways. Prior research has indicated that prenatal exposure to dexamethasone (PDE) heightens the risk of cognitive and emotional disorders in offspring. Axonal development impairment is a frequent pathological underpinning for neuronal dysfunction in these disorders, yet it remains unclear if it plays a role in the neural damage induced by PDE in the offspring. Through RNA-seq and bioinformatics analysis, we found that various signaling pathways related to nervous system development, including axonal development, were altered in the hippocampus of PDE offspring. Among them, the Sonic Hedgehog (SHH) signaling pathway was the most significantly altered and crucial for axonal development. By using miRNA-seq and targeting miRNAs and glucocorticoid receptor (GR) expression, we identified miR-210-3p and miR-362-5p, which can target and suppress SHH expression. Their abnormal high expression was associated with GR activation in PDE fetal rats. Further testing of PDE offspring rats and infant peripheral blood samples exposed to dexamethasone in utero showed that SHH expression was significantly decreased in peripheral blood mononuclear cells (PBMCs) and was positively correlated with SHH expression in the hippocampus and the expression of the axonal development marker growth-associated protein-43. In summary, PDE-induced hippocampal GR-miR-210-3p/miR-362-5p-SHH signaling axis changes lead to axonal developmental damage. SHH expression in PBMCs may reflect axonal developmental damage in PDE offspring and could serve as a warning marker for fetal axonal developmental damage.
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Axônios , Dexametasona , Proteínas Hedgehog , Hipocampo , MicroRNAs , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Dexametasona/toxicidade , Dexametasona/efeitos adversos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Feminino , Ratos , Gravidez , Axônios/efeitos dos fármacos , Axônios/metabolismo , Axônios/patologia , Masculino , Ratos Sprague-Dawley , Humanos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.
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Axônios , Concussão Encefálica , Modelos Animais de Doenças , Caracteres Sexuais , Animais , Feminino , Axônios/patologia , Concussão Encefálica/patologia , Masculino , Suínos , Encéfalo/patologiaRESUMO
Reduced ocular perfusion likely contributes to glaucomatous damage at the optic nerve head (ONH). In recent decades, investigators have focused heavily on ocular perfusion pressure and other factors affecting blood flow to the eye. Comparatively, far less attention has been focused on the blood vessels themselves. Here, we asked whether glaucomatous individuals exhibit anatomical deficiencies (i.e., fewer blood vessels) in their ONH blood supply. To answer this question, we performed a systematic literature review to (1) determine how many studies have reported measuring blood vessels in the ONH and (2) whether these studies reported differences in blood vessel quantity. Additionally, we report a method for quantifying blood vessels in ex vivo human ONH preparations, including an ONH from an individual with glaucoma. Our results show that only two studies in the past 50 years have published data concerning blood vessel density in glaucomatous ONHs. Interestingly, both studies reported decreased blood vessel density in glaucoma. Consistent with this finding, we also report reduced blood vessel numbers in the superolateral quadrant of a glaucomatous individual's ONH. Vascularity in the three remaining quadrants was similar to control. Together, our findings raise the interesting possibility that individuals with a relatively sparse ONH blood supply are more likely to develop glaucoma. Future studies with larger sample sizes and more thorough quantification are necessary to determine the link more accurately between glaucoma and the blood supply to the ONH.
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BACKGROUND: Atrophied lesion volume (aLV), a proposed biomarker of disability progression in multiple sclerosis (MS) and transition into progressive MS (PMS), depicts chronic periventricular white matter (WM) pathology. Meningeal infiltrates, imaged as leptomeningeal contrast enhancement (LMCE), are linked with greater cortical pathology. OBJECTIVES: To determine the relationship between serum-derived proteomic data with the development of aLV and LMCE in a heterogeneous group of people with MS (pwMS). METHODS: Proteomic and MRI data for 202 pwMS (148 clinically isolated syndrome /relapsing-remitting MS and 54 progressive MS (PMS)) were acquired at baseline and at 5.4-year follow-up. The concentrations of 21 proteins related to multiple MS pathophysiology pathways were derived using a custom-developed Proximity Extension Assay on the Olink™ platform. The accrual of aLV was determined as the volume of baseline T2-weighted lesions that were replaced by cerebrospinal fluid over the follow-up. Regression models and age-adjusted analysis of covariance (ANCOVA) were used. RESULTS: Older age (standardized beta = 0.176, p = 0.022), higher glial fibrillary acidic protein (standardized beta = 0.312, p = 0.001), and lower myelin oligodendrocyte glycoprotein levels (standardized beta = -0.271, p = 0.002) were associated with accrual of aLV over follow-up. This relationship was driven by the pwPMS population. The presence of LMCE at the follow-up visit was not predicted by any baseline proteomic biomarker nor cross-sectionally associated with any protein concentration. CONCLUSION: Proteomic markers of glial activation are associated with chronic lesional WM pathology (measured as aLV) and may be specific to the progressive MS phenotype. LMCE presence in MS does not appear to relate to proteomic measures.
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Atrofia , Imageamento por Ressonância Magnética , Neuroglia , Proteômica , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Neuroglia/patologia , Neuroglia/metabolismo , Atrofia/patologia , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Crônica Progressiva/líquido cefalorraquidiano , Esclerose Múltipla/patologia , Esclerose Múltipla/diagnóstico por imagem , Progressão da Doença , Inflamação/patologia , Inflamação/diagnóstico por imagem , Proteína Glial Fibrilar Ácida/metabolismo , Biomarcadores , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
A concussion is the mildest form of a mild traumatic brain injury (tbi) and resembles the most prevalent type of sports associated tbi. Diffuse axonal injuries, the main pathophysiological mechanism of concussion, leads to disruption of communication between different brain areas. The resulting clinical symptoms may relate to several clinical domains (cognition, fatigue, anxiety disorders, headaches/migraines or vestibulo-ocular problems), all of which need to be assessed in a clinical screening during an evaluation for possible concussion. Appropriate and consensus-based protocols to conduct clinical exams are provided by the Concussion in Sport Group (Sport Concussion Assessment Tool (SCAT), Sport Concussion Office Assessment Tool (SCOAT)) and should be used in the most up-to-date version. Therapeutically, slowly and incrementally increasing sub symptomatic activation consisting of daily routine activities, aerobic and cognitive exercises should be introduced early after the trauma. Education about concussion should be geared towards target audiences and will then greatly contribute to adherence and acceptance of medical management.