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Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to reduce innate immune activation in an in vitro model of microglial activation using the blood product hemoglobin (Hgb). We then utilized azithromycin in our in vivo model of IVH, using intraventricular blood injection into the lateral ventricle of post-natal day 5 rat pups. In both models, azithromycin modulated innate immune activation by several outcome measures including mitochondrial bioenergetic analysis, cytokine expression and flow cytometric analysis. This suggests that azithromycin, which is safe for neonates, could hold promise for modulating innate immune activation after IVH.
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Lesões Encefálicas , Hidrocefalia , Ratos , Animais , Azitromicina/farmacologia , Encéfalo/patologia , Hemorragia Cerebral/patologia , Hidrocefalia/etiologia , Lesões Encefálicas/patologia , Hemoglobinas/farmacologiaRESUMO
BACKGROUND: Stereoelectroencephalography (SEEG) remains critical in guiding epilepsy surgery. Robot-assisted techniques have shown promise in improving SEEG implantation outcomes but have not been directly compared. In this single-institution series, we compared ROSA and Stealth AutoGuide robots in pediatric SEEG implantation. METHODS: We retrospectively reviewed 21 sequential pediatric SEEG implantations consisting of 6 ROSA and 15 AutoGuide procedures. We determined mean operative time, time per electrode, root mean square (RMS) registration error, and surgical complications. Three-dimensional radial distances were calculated between each electrode's measured entry and target points with respective errors from the planned trajectory line. RESULTS: Mean overall/per electrode operating time was 73.5/7.5 minutes for ROSA and 126.1/10.9 minutes for AutoGuide (P = 0.030 overall, P = 0.082 per electrode). Mean RMS registration error was 0.77 mm (0.55-0.93 mm) for ROSA and 0.6 mm (0.2-1.0 mm) for AutoGuide (P = 0.26). No procedures experienced complications. The mean radial (entry point error was 1.23 ± 0.11 mm for ROSA and 2.65 ± 0.12 mm for AutoGuide (P < 0.001), while the mean radial target point error was 1.86 ± 0.15 mm for ROSA and 3.25 ± 0.16 mm for AutoGuide (P < 0.001). CONCLUSIONS: Overall operative time was greater for AutoGuide procedures, although there was no statistically significant difference in time per electrode. Both systems are highly accurate with no significant RMS error difference. While the ROSA robot yielded significantly lower entry and target point errors, both robots are safe and reliable for deep electrode insertion in pediatric epilepsy.
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Epilepsia Resistente a Medicamentos , Epilepsia , Procedimentos Cirúrgicos Robóticos , Criança , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Eletroencefalografia/métodos , Técnicas Estereotáxicas , Epilepsia/cirurgia , Eletrodos Implantados , Epilepsia Resistente a Medicamentos/cirurgiaRESUMO
Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1ß secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1ß secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1ß secretion. While IL-1ß release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.
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Doenças da Córnea , Pseudomonas aeruginosa , Animais , Camundongos , Inflamassomos , Neutrófilos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Gravidade do PacienteRESUMO
Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions of Pediatric Neurosurgery and Pediatric Plastic Surgery at UTHealth Houston evaluated 140 children under 36 months of age with suspected craniosynostosis by physical examination and subsequently ordered CT imaging for preoperative planning. Twenty-three patients received a clinical diagnosis of multi-sutural or syndromic craniosynostosis that was confirmed by CT. One hundred seventeen patients were diagnosed with single suture craniosynostosis on clinical examination and follow-up CT confirmed suture fusion in 109 (93.2%) patients and identified intracranial anomalies in 7 (6.0%) patients. These patients underwent surgical correction. Eight (6.8%) patients showed no evidence of craniosynostosis on CT imaging. Treatment for patients without fused sutures included molding helmets and observation alone. This evidence suggests that physical examination alone may be inadequate to accurately diagnose single suture synostosis, and surgery without preoperative CT evaluation could lead to unindicated procedures.
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Craniossinostoses , Humanos , Criança , Lactente , Estudos Retrospectivos , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Crânio/cirurgia , Exame Físico , Procedimentos Neurocirúrgicos , Suturas Cranianas/diagnóstico por imagem , Suturas Cranianas/cirurgia , Suturas Cranianas/anormalidadesRESUMO
BACKGROUND: Inflammation and white matter injury are consequences of neonatal intraventricular hemorrhage (IVH). Both white matter and the neuroimmune system are developing during the time which IVH occurs and its consequences develop. IVH has been studied in many different animal models; however, the effects of IVH occurring at different developmental time points in the same model have not been examined. Understanding how the timing of IVH affects outcome may provide important insights into both IVH pathophysiology and innate immune development. METHODS: We used intraventricular injection of lysed whole blood to model neonatal IVH in postnatal day (P)2 and P5 rats. Flow cytometry was used to detect innate immune activation. MRI was used to screen animals for the development of increased ventricular size. Immunohistochemistry for myelin basic protein was used to quantify white matter and corpus callosum thickness. RESULTS: P5 animals exhibited significant increases in several measures of classically pro-inflammatory innate immune activation that P2 animals did not. Animals with IVH induced at P5 also developed ventricular enlargement visible on MRI whereas animals with IVH induced at P2 did not. On histological analysis, there were no significant effects of IVH in P2 animals, but IVH in P5 animals reduced white matter labeling and corpus callosum thickness. CONCLUSIONS: IVH induces a strong innate inflammatory response in P5 as well as changes in ventricular size and reduction of white matter. P2 animals do not exhibit significant changes in innate immune activation or white matter structure after IVH. This suggests that white matter pathology from IVH is due in part to innate immune activation; and that the developmental stage of the innate immune system is a key determinant of IVH pathology.
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Substância Branca , Animais , Ratos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Imageamento por Ressonância Magnética , Corpo Caloso/patologia , Imunidade InataRESUMO
Background: Inflammation and white matter injury are consequences of neonatal intraventricular hemorrhage (IVH). Both white matter and the neuroimmune system are developing during which IVH and its consequences occur. IVH has been studied in many different animal models; however, the effects of IVH occurring at different developmental time points in the same model has not been examined. Examining how the timing of IVH affects the ultimate outcome of IVH may provide important insights into IVH pathophysiology. Methods: We used intraventricular injection of lysed whole blood to model neonatal IVH in postnatal day (P)2 and P5 rats. Flow cytometry was used to detect innate immune activation. MRI was used to screen animals for the development of increased ventricular size. Immunohistochemistry for myelin basic protein was used to assess white matter pathology. Results: The acute response of the innate immune system at these time points differed, with P5 animals exhibiting significant increases in several measures of classically pro-inflammatory innate immune activation that P2 animals did not. Animals with IVH induced at P5 also developed ventricular enlargement visible on MRI whereas animals with IVH induced at P2 did not. On histological analysis, there were no significant effects of IVH in P2 animals, but IVH in P5 animals induced a reduction in several measures of white matter integrity. Conclusions: IVH induces a strong innate inflammatory response in P5 animals that correlates with changes in ventricular size and white matter. P2 animals did not exhibit any significant changes in innate immune activation or white matter structure after IVH. This suggests that the white matter pathology from IVH is due in part to innate immune activation; and that the developmental stage of the innate immune system is a key determinant of IVH pathology.
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Pyroptosis is a proinflammatory mode of lytic cell death mediated by accumulation of plasma membrane (PM) macropores composed of gasdermin-family (GSDM) proteins. It facilitates two major functions in innate immunity: (i) elimination of intracellular replicative niches for pathogenic bacteria; and (ii) non-classical secretion of IL-1 family cytokines that amplify host-beneficial inflammatory responses to microbial infection or tissue damage. Physiological roles for gasdermin D (GSDMD) in pyroptosis and IL-1ß release during inflammasome signaling have been extensively characterized in macrophages. This involves cleavage of GSDMD by caspase-1 to generate GSDMD macropores that mediate IL-1ß efflux and progression to pyroptotic lysis. Neutrophils, which rapidly accumulate in large numbers at sites of tissue infection or damage, become the predominant local source of IL-1ß in coordination with their potent microbiocidal capacity. Similar to macrophages, neutrophils express GSDMD and utilize the same spectrum of diverse inflammasome platforms for caspase-1-mediated cleavage of GSDMD. Distinct from macrophages, neutrophils possess a remarkable capacity to resist progression to GSDMD-dependent pyroptotic lysis to preserve their viability for efficient microbial killing while maintaining GSDMD-dependent mechanisms for export of bioactive IL-1ß. Rather, neutrophils employ cell-specific mechanisms to conditionally engage GSDMD-mediated pyroptosis in response to bacterial pathogens that use neutrophils as replicative niches. GSDMD and pyroptosis have also been mechanistically linked to induction of NETosis, a signature neutrophil pathway that expels decondensed nuclear DNA into extracellular compartments for immobilization and killing of microbial pathogens. This review summarizes a rapidly growing number of recent studies that have produced new insights, unexpected mechanistic nuances, and some controversies regarding the regulation of, and roles for, neutrophil inflammasomes, pyroptosis, and GSDMs in diverse innate immune responses.
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Inflamassomos , Piroptose , Humanos , Piroptose/fisiologia , Inflamassomos/metabolismo , Neutrófilos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Gasderminas , Caspase 1/metabolismo , Transdução de SinaisRESUMO
Neonatal intraventricular hemorrhage (IVH) is a common consequence of premature birth and leads to brain injury, posthemorrhagic hydrocephalus (PHH), and lifelong neurological deficits. While PHH can be treated by temporary and permanent cerebrospinal fluid (CSF) diversion procedures (ventricular reservoir and ventriculoperitoneal shunt, respectively), there are no pharmacological strategies to prevent or treat IVH-induced brain injury and hydrocephalus. Animal models are needed to better understand the pathophysiology of IVH and test pharmacological treatments. While there are existing models of neonatal IVH, those that reliably result in hydrocephalus are often limited by the necessity for large-volume injections, which may complicate modeling of the pathology or introduce variability in the clinical phenotype observed. Recent clinical studies have implicated hemoglobin and ferritin in causing ventricular enlargement after IVH. Here, we develop a straightforward animal model that mimics the clinical phenotype of PHH utilizing small-volume intraventricular injections of the blood breakdown product hemoglobin. In addition to reliably inducing ventricular enlargement and hydrocephalus, this model results in white matter injury, inflammation, and immune cell infiltration in periventricular and white matter regions. This paper describes this clinically relevant, simple method for modeling IVH-PHH in neonatal rats using intraventricular injection and presents methods for quantifying ventricle size post injection.
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Lesões Encefálicas , Hidrocefalia , Animais , Lesões Encefálicas/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemoglobinas , Hidrocefalia/etiologia , Hidrocefalia/patologia , Injeções Intraventriculares , RatosRESUMO
BACKGROUND: Cerebral venous sinus thrombosis (VST) is a complication of head injury and can be secondary to sinus compression by depressed skull fractures. Fracture elevation is a treatment option for VST secondary to extrinsic compression, but conservative management may also be effective. Venous sinuses can also be lacerated from skull fractures, resulting in epidural or subdural hematomas. The authors presented a case of sagittal sinus injury and thrombosis from a depressed skull fracture that caused a subgaleal hematoma. The injury was successfully managed conservatively. OBSERVATIONS: A 14-year-old boy presented after a head injury with a diastatic, depressed parietal bone fracture. Computed tomography venogram showed disruption and occlusion of the superior sagittal sinus with a subgaleal hematoma in continuity with the injured sagittal sinus. Because of concern for hemorrhage if tamponade on the sinus was removed, the patient was treated nonsurgically. At follow-up, the sinus had recanalized and the fracture had healed. LESSONS: Skull fractures with underlying sinus thrombosis can be managed conservatively with good outcome. Careful assessment for venous sinus injury should be made before undertaking fracture elevation to relieve sinus compression.
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The purpose of this investigation was to compare changes in circulating lymphocyte subset cell counts between high-intensity interval exercise (HIIE), sprint interval exercise (SIE), and moderate-intensity continuous exercise (MICE). Recreationally active men (n â= â11; age: 23 â± â4 âyr; height: 179.9 â± â4.5 âcm; body mass: 79.8 â± â8.7 âkg; body fat %:12.6 â± â3.8%; VÌO2max: 46.6 â± â3.9 âmlâ kg-1â min-1) completed a maximal graded exercise test to determine maximal oxygen uptake (VÌO2max) and three duration-matched cycling trials (HIIE, SIE, and MICE) in a randomized, counterbalanced fashion. HIIE consisted of fifteen 90-s bouts at 85% VÌO2max interspersed with 90-s active recovery periods. SIE consisted of fifteen 20-s bouts at 130% maximal power and 160-s active recovery periods. MICE was a continuous bout at 65% VÌO2max. Total exercise duration was 53 âmin in all three trials, including warm-up and cool-down. Blood was collected before, immediately post, 30 âmin, 2 âh, 6 âh, and 24 âh post-exercise. Changes in lymphocyte subset counts, and surface expression of various markers were analyzed via flow cytometry. Changes were assessed using mixed model regression analysis with an autoregressive first order repeated measures correction. Significant decreases were observed in absolute counts of CD56dim NK cells, CD19+ B cells, CD4+ T cells, and CD8+ T cells 30 âmin and 24-h post-exercise in all three trials. Despite resulting in greater total work and oxygen consumption, MICE elicited similar changes in lymphocyte subset counts and receptor expression compared to both SIE and HIIE. Similarly, while the two interval trials resulted in differing oxygen consumption and total work, no differences in the lymphocyte response were observed. Though both forms of exercise resulted in declines in circulating lymphocyte cell counts, neither exercise type provides an immune-related advantage when matched for duration.
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This study sought to determine relationships between hexagonal barbell (HBB) deadlift one-repetition maximum (1-RM) and force-time characteristics of maximal isometric pulls. Twenty-three healthy adults (13 men [8 trained], 10 women [4 trained]) completed three visits consisting of a familiarization and anthropometrics session, a HBB deadlift 1-RM session, and a performance session with three maximal isometric pulls at three positions: lift-off (FLOOR), knee-passing (KNEE), and mid-thigh (MT). Correlation analyses assessed relationships between 1-RM and force-time characteristics at each position with significance set a priori at α ≤ 0.05. Correlation coefficients between 1-RM and force-time characteristics at all positions presented large to very large relationships to peak force (PF; r = 0.695-0.879, p ≤ 0.001), large to very large relationships to all time-specific force variables (r = 0.506-0.812; p ≤ 0.014), moderate to very large relationships between rate of force development (RFD) time-bands (r = 0.430-0.752; p ≤ 0.041), and large to very large relationships to impulse (r = 0.575-0.778; p ≤ 0.004). Collectively, more very large effect sizes (r = 0.7-0.89) were observed at FLOOR (n = 8) and KNEE (n = 6) than MT (n = 0). PF at FLOOR and KNEE presented as strongest predictors of maximal strength in the 1-RM HBB deadlift. The observed differences between positions may be due to exercise-specific disadvantageous positions commonly observed as isometric sticking points. Coaches should consider incorporating isometric pulls from the lift-off or knee passing positions as it appears to be better related to maximal strength than the isometric mid-thigh pull.
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Oligodendrocyte progenitor cells (OPCs) in the infant brain give rise to mature oligodendrocytes that myelinate CNS axons. OPCs are particularly vulnerable to oxidative stress that occurs in many forms of brain injury. One common cause of infant brain injury is neonatal intraventricular hemorrhage (IVH), which releases blood into the CSF and brain parenchyma of preterm infants. Although blood contains the powerful oxidant hemoglobin, the direct effects of hemoglobin on OPCs have not been studied. We utilized a cell culture system to test if hemoglobin induced free radical production and mitochondrial dysfunction in OPCs. We also tested if phenelzine (PLZ), an FDA-approved antioxidant drug, could protect OPCs from hemoglobin-induced oxidative stress. OPCs were isolated from Sprague Dawley rat pups and exposed to hemoglobin with and without PLZ. Outcomes assessed included intracellular reactive oxygen species levels using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent dye, oxygen consumption using the XFe96 Seahorse assay, and proliferation measured by BrdU incorporation assay. Hemoglobin induced oxidative stress and impaired mitochondrial function in OPCs. PLZ treatment reduced hemoglobin-induced oxidative stress and improved OPC mitochondrial bioenergetics. The effects of hemoglobin and PLZ on OPC proliferation were not statistically significant, but showed trends towards hemoglobin reducing OPC proliferation and PLZ increasing OPC proliferation (P=0.06 for both effects). Collectively, our results indicate that hemoglobin induces mitochondrial dysfunction in OPCs and that antioxidant therapy reduces these effects. Therefore, antioxidant therapy may hold promise for white matter diseases in which hemoglobin plays a role, such as neonatal IVH.
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Hemoglobinas/farmacologia , Mitocôndrias/efeitos dos fármacos , Oligodendroglia/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , L-Lactato Desidrogenase , Mitocôndrias/metabolismo , Consumo de Oxigênio , Fenelzina/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Células-TroncoRESUMO
Sagittal craniosynostosis, the most common form of craniosynostosis, affects 1 per 1000 live births. The main surgical treatments include endoscopic suturectomy and open cranial vault remodeling. This video describes an open reconstruction method, including strip resection of the sagittal suture, biparietal craniotomies with spiral cut cranioplasty, and barrel staves of the posterior occiput. Ideally used between 4 and 15 months of age, this approach takes advantage of the flexibility of the cranial bones to expand, allowing for immediate and long-term increases of the parietal width and correction of cosmetic deformity, without necessitating the use of cranial molding devices postoperatively. The video can be found here: https://vimeo.com/516699203.
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BACKGROUND: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model. METHODS: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus. RESULTS: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus. CONCLUSIONS: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH.
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Comportamento Animal , Encéfalo/fisiopatologia , Aprendizagem em Labirinto , Transtornos Neurocognitivos/etiologia , Hemorragia Subaracnóidea/etiologia , Animais , Encéfalo/patologia , Cisterna Magna , Modelos Animais de Doenças , Reação de Fuga , Injeções , Masculino , Camundongos Endogâmicos C57BL , Degeneração Neural , Transtornos Neurocognitivos/patologia , Transtornos Neurocognitivos/fisiopatologia , Transtornos Neurocognitivos/psicologia , Tempo de Reação , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia , Hemorragia Subaracnóidea/psicologia , Natação , Fatores de TempoRESUMO
OBJECTIVE: Neonatal intraventricular hemorrhage (IVH) leads to posthemorrhagic hydrocephalus (PHH), brain injury, and long-term disability. Current therapy for IVH is based on treating PHH but does not address the underlying brain injury. In order to develop pharmacological treatment for IVH, there must be a better understanding of the underlying pathology of this disease. This study was designed to determine the time course of the acute inflammation and oxidative stress that may underlie the progressive pathology of IVH. The authors sought to understand the temporal relationships among inflammation, oxidative stress, and white matter pathology in a rat model of IVH. METHODS: A rat model of IVH consisting of hemoglobin injection into the lateral ventricle was used. Tissue was analyzed via biochemical and histological methods to map the spatiotemporal distribution of innate immune activation and oxidative stress. White matter was quantified using both immunohistochemistry and Western blot for myelin basic protein (MBP) in the corpus callosum. RESULTS: IVH led to acute induction of inflammatory cytokines, followed by oxidative stress. Oxidative stress was concentrated in white matter, adjacent to the lateral ventricles. Animals with IVH initially gained weight at a lower rate than control animals and had larger ventricles and less MBP than control animals. CONCLUSIONS: Experimental IVH induces global inflammation throughout the brain and oxidative stress concentrated in the white matter. Both of these phenomena occur early after IVH. This has implications for human neonates with immature white matter that is exquisitely sensitive to inflammation and oxidative stress. Antiinflammatory or antioxidant therapy for IVH may need to be initiated early in order to protect developing white matter.
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Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.
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Malformações Vasculares do Sistema Nervoso Central/terapia , Hemorragia Cerebral/terapia , Hidrocefalia/terapia , Vértebras Lombares , Derivação Ventriculoperitoneal/métodos , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Criança , Diagnóstico Diferencial , Drenagem/métodos , Embolização Terapêutica/métodos , Seguimentos , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Vértebras Lombares/irrigação sanguínea , Vértebras Lombares/diagnóstico por imagem , MasculinoRESUMO
Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.
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Malformações Vasculares do Sistema Nervoso Central/cirurgia , Hemorragia Cerebral/cirurgia , Hidrocefalia/cirurgia , Região Lombossacral/cirurgia , Malformações Vasculares do Sistema Nervoso Central/complicações , Hemorragia Cerebral/etiologia , Criança , Embolização Terapêutica , Humanos , Hidrocefalia/etiologia , Masculino , Derivação VentriculoperitonealRESUMO
OBJECTIVE: The authors sought to determine if hydrocephalus caused a proinflammatory state within white matter as is seen in many other forms of neonatal brain injury. Common causes of hydrocephalus (such as trauma, infection, and hemorrhage) are inflammatory insults themselves and therefore confound understanding of how hydrocephalus itself affects neuroinflammation. Recently, a novel animal model of hydrocephalus due to a genetic mutation in the Ccdc39 gene has been developed in mice. In this model, ciliary dysfunction leads to early-onset ventriculomegaly, astrogliosis, and reduced myelination. Because this model of hydrocephalus is not caused by an antecedent proinflammatory insult, it was utilized to study the effect of hydrocephalus on inflammation within the white matter of the corpus callosum. METHODS: A Meso Scale Discovery assay was used to measure levels of proinflammatory cytokines in whole brain from animals with and without hydrocephalus. Immunohistochemistry was used to measure macrophage activation and NG2 expression within the white matter of the corpus callosum in animals with and without hydrocephalus. RESULTS: In this model of hydrocephalus, levels of cytokines throughout the brain revealed a more robust increase in classic proinflammatory cytokines (interleukin [IL]-1ß, CXCL1) than in immunomodulatory cytokines (IL-10). Increased numbers of macrophages were found within the corpus callosum. These macrophages were polarized toward a proinflammatory phenotype as assessed by higher levels of CD86, a marker of proinflammatory macrophages, compared to CD206, a marker for antiinflammatory macrophages. There was extensive structural damage to the corpus callosum of animals with hydrocephalus, and an increase in NG2-positive cells. CONCLUSIONS: Hydrocephalus without an antecedent proinflammatory insult induces inflammation and tissue injury in white matter. Future studies with this model will be useful to better understand the effects of hydrocephalus on neuroinflammation and progenitor cell development. Antiinflammatory therapy for diseases that cause hydrocephalus may be a powerful strategy to reduce tissue damage.
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Aneurysmal subarachnoid hemorrhage (SAH) is rare in neonates. The authors present a unique report of a neonate with SAH from anterior inferior cerebellar artery (AICA) aneurysm rupture that was successfully treated with Onyx embolization. This case report demonstrates the utility of Onyx embolization for posterior circulation aneurysms in neonates and the successful management of SAH in this population.
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Aneurisma Roto/terapia , Dimetil Sulfóxido/uso terapêutico , Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Polivinil/uso terapêutico , Tantálio/uso terapêutico , Aneurisma Roto/complicações , Humanos , Recém-Nascido , Aneurisma Intracraniano/complicações , Masculino , Hemorragia Subaracnóidea/etiologiaRESUMO
BACKGROUND: Choroid plexus carcinoma (CPC) is a rare, malignant tumor occurring more commonly in children than adults. This case report describes the clinical course of a 3-year-old boy with a rare case of metastatic CPC with a novel TP53 mutation. CASE DESCRIPTION: A 3-year-old boy presented with postconcussive symptoms after a fall. Computed tomography and magnetic resonance imaging revealed lesions in the suprasellar cistern, left lateral ventricle, and cauda equina. The tumor was diagnosed as choroid plexus carcinoma with a novel TP53 V216M somatic mutation. The patient underwent resection of the left lateral ventricle lesion. CONCLUSION: We describe a case of CPC with highly metastatic characteristics and a novel TP53 mutation. Our report implicates TP53 in the pathogenesis of pediatric CPC, and we emphasize that CPC in children should prompt careful consideration of TP53 status to inform prognosis and clinical treatment.