Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury

Ichkova, Aleksandra; Rodriguez‐Grande, Beatriz; Bar, Claire; Villega, Frédéric; Konsman, Jan Pieter; Badaut, Jérôme

doi:10.1016/j.neuint.2017.03.022

Cited by 24 publications

(29 citation statements)

References 116 publications

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“…The pathophysiology of TBI Traumatic brain injury is characterized by instant damage to mechanical force and delayed damage to the subsequent pathophysiological processes [21]. The mechanical force directly leads to neuronal or diffuse axonal damage and vascular disruption, followed by secondary injury mediated by extensive neuroinflammation, dysfunction of the BBB, oxidative stress, and apoptosis [22][23][24][25][26]. While the immediate primary injury is considered untreatable, the delayed secondary injury gives a window for intervention and has, therefore, attracted a lot of attention [27].…”

Section: Introductionmentioning

confidence: 99%

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

et al. 2020

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Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. Traumatic brain injury induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. As a way of coping with the trauma, astrocytes respond in diverse mechanisms that result in reactive astrogliosis. Astrocytes are involved in the physiopathologic mechanisms of TBI in an extensive and sophisticated manner. Notably, astrocytes have dual roles in TBI, and some astrocyte-derived factors have double and opposite properties. Thus, the suppression or promotion of reactive astrogliosis does not have a substantial curative effect. In contrast, selective stimulation of the beneficial astrocytederived molecules and simultaneous attenuation of the deleterious factors based on the spatiotemporalenvironment can provide a promising astrocyte-targeting therapeutic strategy. In the current review, we describe for the first time the specific dual roles of astrocytes in neuronal plasticity and reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair of the blood-brain barrier, and glial scar formation after TBI. We have also classified astrocyte-derived factors depending on their neuroprotective and neurotoxic roles to design more appropriate targeted therapies.

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Section: Introductionmentioning

confidence: 99%

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

et al. 2020

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“…13 Brain trauma or intra-striatal CINC-1 injection exert more severe brain edema, CBF dysregulation and injury outcome in juvenile than in adult rodents. [17][18][19]45,46 Impaired vascular reactivity has been reported in pediatric brain trauma models in several species, 47 changes not necessarily associated with structural barrier breakdown. 19 In CAIS model, we demonstrate that monocyte/microglial CX3CR1-CCR2 signaling contributes to neurovascular disturbances and injury.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings of the overall markedly reduced vascular coverage and preferential loss of smaller size vessels and capillaries in ischemic-reperfused regions are consistent with profound long-lasting vascular changes reported in a model of pediatric brain trauma. 18,47 While we focus on consequences of disruption of particular pathways in microglia-monocyte function for BBB leakage and injury after acute CAIS, altered interactions will likely have broad range long-lasting effects. For example, microglia were demonstrated to regulate the density of oligodendrocytes precursor cells (OPCs) and myelination early postnatal 70 and possess ''immune memory'' of previous challenge.…”

Section: Discussionmentioning

confidence: 99%

CX3CR1-CCR2-dependent monocyte-microglial signaling modulates neurovascular leakage and acute injury in a mouse model of childhood stroke

Faustino

Chip

Derugin

et al. 2019

J Cereb Blood Flow Metab

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Stroke is among the top 10 causes of death in children. The developmental stage of the brain is central to stroke pathophysiology. The incidence of childhood arterial ischemic stroke (CAIS) is lower than of perinatal arterial ischemic stroke but the rate of recurrence is strikingly high. Vascular inflammation is seen as major contributor to CAIS but the mechanisms that govern structural-functional basis of vascular abnormalities remain poorly understood. To identify the contribution of immune-neurovascular interactions to CAIS, we established stroke model in postnatal day 21 (P21) mice. We demonstrate acute functional deficits and histological injury and chronic MRI-identifiable injury, brain atrophy and marked derangements in the vascular network. In contrast to negligible albumin leakage and neutrophil infiltration following acute perinatal stroke, CAIS leads to significantly increased albumin leakage and neutrophil infiltration in injured regions of wild type mice and mice with functional CX3CR1-CCR2 receptors. In mice with dysfunctional CX3CR1-CCR2 signaling, extravascular albumin leakage is significantly attenuated, infiltration of injurious Ccr2+-monocytes essentially aborted, accumulation of Ly6G+ neutrophils reduced and acute injury attenuated. Unique identifiers of microglia and monocytes revealed phenotypic changes in each cell subtype of the monocyte lineage after CAIS. Taken together, CX3CR1-CCR2-dependent microglia-monocyte signaling contributes to cerebrovascular leakage, inflammation and CAIS injury.

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“…Entre los trastornos emocionales y conductuales asociados al TCE está la depresión, la ansiedad e irritabilidad (54,57,58) ; datos similares reporta la Universidad de Melbourne en Australia (55) . Con respecto al área cerebral comprometida se presentan diferentes manifestaciones, en el caso del lóbulo frontal o temporal puede ocasionar dificultad para regular o controlar la conducta, déficit en la memoria y alteraciones sociales y físicas (13,15,52,59,60) . En el 2017 se realizó una revisión sistemática de la calidad de vida relacionada con la salud en los niños latinoamericanos con TCE, se encontró que los pacientes que sufrieron TCE moderado-severo se ven afectados en su calidad de vida durante los años siguientes al daño cerebral, siendo la esfera psicosocial la más afectada, esta se manifiesta en problemas escolares tanto de relaciones interpersonales como de rendimiento académico (61) .…”

Section: Discussionunclassified

Traumatismo craneoencefálico en niños. Hospital General de Medellín y Clínica Somer de Rionegro, 2010-2017

Jiménez-Aguilar

Montoya-Jaramillo

Benjumea-Bedoya

et al. 2019

Iatreia

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Objetivo: describir las características sociodemográficas, aspectos clínicos y complicaciones de los niños de 0 a 10 años de edad que sufrieron traumatismo craneoencefálico, atendidos en el Hospital General de Medellín y en la Clínica Somer de Rionegro entre los años 2010 y 2017.Métodos: estudio descriptivo retrospectivo, toma como fuente de información las historias clínicas de los niños con diagnósticos relacionados con el traumatismo craneoencefálico entre 2010-2017. Se calcularon las proporciones de las variables sociodemográficas, circunstanciales, espacio-temporales y clínicas.Resultados: se encontraron 224 pacientes con traumatismo craneoencefálico, el 64,7 % de los casos fueron de sexo masculino, la edad promedio fue de 4,5 años. El trauma ocurrió con mayor frecuencia en el domicilio del paciente entre los días de la semana en las horas de la tarde. La causa principal del trauma fue caída (75 %), seguido por accidentes de tránsito (13,3 %). La gravedad del traumatismo se midió con la escala de coma de Glasgow, el 78 % fue leve, hubo un caso fatal y 7 (3 %) tuvieron complicaciones motoras durante la hospitalización.Conclusión: los hallazgos de este estudio coinciden con las principales características del traumatismo craneoencefálico de la población pediátrica en el mundo, amplía la información regional y local para el desarrollo de estrategias de prevención, diagnóstico y seguimiento a largo plazo de los pacientes.

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Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury

Cited by 24 publications

References 116 publications

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

CX3CR1-CCR2-dependent monocyte-microglial signaling modulates neurovascular leakage and acute injury in a mouse model of childhood stroke

Traumatismo craneoencefálico en niños. Hospital General de Medellín y Clínica Somer de Rionegro, 2010-2017

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