RESUMEN
INTRODUCTION: Brain contusion is a prevalent traumatic brain injury (TBI) in low-age children, bearing the potential for coma and fatality. Hence, it is imperative to undertake comprehensive research in this field. METHODS: This study employed 4-week-old piglets as surrogates for children and introduced self-designed devices for both free-fall drop impact tests and drop-hammer impact tests. The study explored the characteristics of brain contusion and dynamic responses of brain under these distinct testing conditions. RESULTS: Brain contusions induced by free-fall and drop-hammer conditions both were categorized as the coup injury, except that slight difference in the contusion location was observed, with contusion occurring mainly in the surrounding regions beneath the impact location under free-fall condition and the region just right beneath the impact location under drop-hammer condition. Analysis of impact force and intracranial pressure (ICP) curves indicated similar trends in impact forces under both conditions, yet different trends in ICPs. Further examination of the peak impact forces and ICPs elucidated that, with increasing impact energy, the former followed a combined power and first-order polynomial function, while the latter adhered to a power function. The brain contusion was induced at the height (energy) of 2 m (17.2 J), but not at the heights of 0.4, 0.7, 1, 1.35 and 1.7 m, when the vertex of the piglet head collided with a rigid plate. In the case of a cylindrical rigid hammer (cross-sectional area constituting 40 % of the parietal bone) striking the head, the brain contusion was observed under the energy of 21.9 J, but not under energies of 8.1 J, 12.7 J and 20.3 J. Notably, the incidence of brain contusion was more pronounced under the free-fall condition. CONCLUSIONS: These findings not only facilitate a comprehensive understanding of brain contusion dynamics in pediatric TBIs, but also contribute to the validation of theories and finite element models for piglet heads, which are commonly employed as surrogates for children.
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Contusión Encefálica , Modelos Animales de Enfermedad , Animales , Porcinos , Contusión Encefálica/fisiopatología , Humanos , Presión Intracraneal/fisiología , Fenómenos Biomecánicos , Lesiones Traumáticas del Encéfalo/fisiopatología , Encéfalo/fisiopatologíaRESUMEN
BACKGROUND: Patients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions. METHODS: This observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60-70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than - 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months. RESULTS: Among the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome. CONCLUSIONS: In patients with TBI with significant contusions, CPP within 60-70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice.
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Contusión Encefálica , Lesiones Traumáticas del Encéfalo , Cuidados Críticos , Presión Intracraneal , Humanos , Masculino , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Femenino , Persona de Mediana Edad , Adulto , Anciano , Presión Intracraneal/fisiología , Contusión Encefálica/fisiopatología , Circulación Cerebrovascular/fisiología , Adulto JovenRESUMEN
Transcranial electrical stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans, and even in animal studies, tcMEPs are used to evaluate neurological dysfunction. However, there is a dearth of reports on extended tcMEP recordings in both animal models and humans. Therefore, this study examined a new technique for stably recording tcMEPs over several weeks in six healthy female Sprague-Dawley rats. We thinned the skull bone using the skull base and spinal surgery technique to reduce electrical resistance for electrical stimulation. tcMEPs were recorded on days 1, 7, 14, 21, and 28 after surgery. The onset latency and amplitude of tcMEPs from the hindlimbs were recorded and evaluated, and histological analysis was performed. Stable amplitude and onset latency could be recorded over several weeks, and histological analysis indicated no complications attributable to the procedure. Thus, our novel technique allows for less invasive, safer, easier, and more stable extended tcMEP recordings than previously reported techniques. The presently reported technique may be applied to the study of various nerve injury models in rats: specifically, to evaluate the degree of nerve dysfunction and recovery in spinal cord injury, cerebral infarction, and brain contusion models.
Asunto(s)
Potenciales Evocados Motores/fisiología , Cráneo/cirugía , Estimulación Transcraneal de Corriente Directa/métodos , Animales , Contusión Encefálica/diagnóstico , Contusión Encefálica/fisiopatología , Contusión Encefálica/cirugía , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatología , Infarto Cerebral/cirugía , Modelos Animales de Enfermedad , Electromiografía , Femenino , Miembro Posterior/fisiología , Humanos , Monitoreo Intraoperatorio/métodos , Procedimientos Neuroquirúrgicos/métodos , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/cirugíaRESUMEN
Traumatic brain injury (TBI) is a substantial cause of disability and death worldwide. Primary head trauma triggers chronic secondary injury mechanisms in the brain that are a focus of therapeutic efforts to treat TBI. Currently, there is no successful clinical strategy to repair brain injury. Cell transplantation therapies have demonstrated promise in attenuating secondary injury mechanisms of neuronal death and dysfunction in animal models of brain injury. In this study, we used a unilateral cortical contusion injury (CCI) model of sensorimotor brain injury to examine the effects of human induced pluripotent stem cell (hiPSC) transplantation on pathology in male and female adult mice. We determined transplanted hiPSC-derived neural stem cells (NSCs) and neuroblasts but not astrocytes best tolerate the injured host environment. Surviving NSC and neuroblast cells were clustered at the site of injection within the deep layers of the cortex and underlying corpus callosum. Cell grafts extended neuritic processes that crossed the midline into the contralateral corpus callosum or continued laterally within the external capsule to enter the ipsilateral entorhinal cortex. To determine the effect of transplantation on neuropathology, we performed sensorimotor behavior testing and stereological estimation of host neurons, astrocytes, and microglia within the contused cortex. These measures did not reveal a consistent effect of transplantation on recovery post-injury. Rather the positive and negative effects of cell transplantation were dependent on the host sex, highlighting the importance of developing patient-specific approaches to treat TBI. Our study underscores the complex interactions of sex, neuroimmune responses and cell therapy in a common experimental model of TBI.
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Contusión Encefálica/fisiopatología , Corteza Cerebral/fisiopatología , Células Madre Pluripotentes Inducidas/trasplante , Destreza Motora/fisiología , Recuperación de la Función/fisiología , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Células-Madre Neurales/fisiología , Factores Sexuales , Trasplante de Células MadreAsunto(s)
Lesiones Traumáticas del Encéfalo/fisiopatología , Fármacos Neuromusculares no Despolarizantes/uso terapéutico , Rocuronio/uso terapéutico , Hemorragia Subaracnoidea Traumática/fisiopatología , Sugammadex/uso terapéutico , Accidentes de Tránsito , Contusión Encefálica/complicaciones , Contusión Encefálica/diagnóstico , Contusión Encefálica/fisiopatología , Contusión Encefálica/terapia , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Manejo de la Enfermedad , Humanos , Intubación Intratraqueal/métodos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Examen Neurológico , Hemorragia Subaracnoidea Traumática/complicaciones , Hemorragia Subaracnoidea Traumática/diagnóstico , Hemorragia Subaracnoidea Traumática/terapiaRESUMEN
BACKGROUND: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI. METHODS: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses. RESULTS: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status. CONCLUSIONS: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.
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Presión Arterial/fisiología , Edema Encefálico/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Hemorragia Intracraneal Traumática/fisiopatología , Presión Intracraneal/fisiología , Adulto , Contusión Encefálica/diagnóstico por imagen , Contusión Encefálica/fisiopatología , Edema Encefálico/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Escala de Coma de Glasgow , Escala de Consecuencias de Glasgow , Homeostasis/fisiología , Humanos , Unidades de Cuidados Intensivos , Hemorragia Intracraneal Traumática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: The purpose of this study was to identify risk factors of mortality for geriatric patients who fell from ground level at home and had a normal physiological examination at the scene. METHODS: Patients aged 65 and above, who sustained a ground level fall (GLF) with normal scene Glasgow Coma Scale (GCS) score 15, systolic blood pressure (SBP) > 90 and <160 mmHg, heart rate ≥ 60 and ≤100 beats per minute) from the 2012-2014 National Trauma Data Bank (NTDB) data sets were included in the study. Patients' characteristics, existing comorbidities [history of smoking, chronic kidney disease (CKD), cerebrovascular accident (CVA), diabetes mellitus (DM), and hypertension (HTN) requiring medication], injury severity scores (ISS), American College of Surgeons' (ACS) trauma center designation level, and outcomes were examined for each case. Risks factors of mortality were identified using bivariate analysis and logistic regression modeling. RESULTS: A total of 40,800 patients satisfied the study inclusion criteria. The findings of the logistic regression model for mortality using the covariates age, sex, race, SBP, ISS, ACS trauma level, smoking status, CKD, CVA, DM, and HTN were associated with a higher risk of mortality (p < .05). The fitted model had an Area under the Curve (AUC) measure of 0.75. CONCLUSION: Cases of geriatric patients who look normal after a fall from ground level at home can still be associated with higher risk of in-hospital death, particularly those who are older, male, have certain comorbidities. These higher-risk patients should be triaged to the hospital with proper evaluation and management.
Asunto(s)
Accidentes por Caídas , Traumatismos Craneocerebrales/epidemiología , Diabetes Mellitus/epidemiología , Fracturas Óseas/epidemiología , Mortalidad Hospitalaria , Hipertensión/epidemiología , Insuficiencia Renal Crónica/epidemiología , Accidente Cerebrovascular/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Contusión Encefálica/epidemiología , Contusión Encefálica/fisiopatología , Vértebras Cervicales/lesiones , Comorbilidad , Traumatismos Craneocerebrales/fisiopatología , Femenino , Fracturas Óseas/fisiopatología , Escala de Coma de Glasgow , Hematoma Intracraneal Subdural/epidemiología , Hematoma Intracraneal Subdural/fisiopatología , Fracturas de Cadera/epidemiología , Fracturas de Cadera/fisiopatología , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Fracturas de las Costillas/epidemiología , Fracturas de las Costillas/fisiopatología , Medición de Riesgo , Factores Sexuales , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/fisiopatología , Hemorragia Subaracnoidea Traumática/epidemiología , Hemorragia Subaracnoidea Traumática/fisiopatología , Centros Traumatológicos , Signos VitalesRESUMEN
Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.
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Lesiones Traumáticas del Encéfalo/fisiopatología , Escala de Consecuencias de Glasgow , Mortalidad Hospitalaria , Escala Resumida de Traumatismos , Accidentes por Caídas , Accidentes de Tránsito , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , Contusión Encefálica/mortalidad , Contusión Encefálica/fisiopatología , Contusión Encefálica/terapia , Traumatismos Difusos del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/mortalidad , Lesiones Traumáticas del Encéfalo/terapia , Hemorragia Cerebral Traumática/mortalidad , Hemorragia Cerebral Traumática/fisiopatología , Hemorragia Cerebral Traumática/terapia , Hemorragia Cerebral Intraventricular/mortalidad , Hemorragia Cerebral Intraventricular/fisiopatología , Hemorragia Cerebral Intraventricular/terapia , Estudios de Cohortes , Femenino , Hematoma Subdural/mortalidad , Hematoma Subdural/fisiopatología , Hematoma Subdural/terapia , Humanos , Puntaje de Gravedad del Traumatismo , Unidades de Cuidados Intensivos , Masculino , Mortalidad , Procedimientos Neuroquirúrgicos , Oportunidad Relativa , Sistema de Registros , Respiración Artificial , Fracturas Craneales/mortalidad , Fracturas Craneales/fisiopatología , Fracturas Craneales/terapia , Hemorragia Subaracnoidea Traumática/mortalidad , Hemorragia Subaracnoidea Traumática/fisiopatología , Hemorragia Subaracnoidea Traumática/terapia , Traqueostomía , VictoriaRESUMEN
Arginine vasopressin (AVP) is a chemical signal in the brain that influences cerebral vascular resistance and brain water permeability. Increases in AVP contribute to the pathophysiology of brain edema following traumatic brain injury (TBI). These effects are mediated through AVP V1a receptors that are expressed in cortical and subcortical brain areas. This exploratory study characterizes the effects of a novel, V1a receptor antagonist, AVN576, on behavioral and magnetic resonance imaging (MRI) measures after severe TBI. Male Sprague Dawley rats were impacted twice producing contusions in the forebrain, putative cerebral edema, and cognitive deficits. Rats were treated with AVN576 after initial impact for 5 days and then tested for changes in cognition. MRI was used to assess brain injury, enlargement of the ventricles, and resting state functional connectivity. Vehicle treated rats had significant deficits in learning and memory, enlarged ventricular volumes, and hypoconnectivity in hippocampal circuitry. AVN576 treatment eliminated the enlargement of the lateral ventricles and deficits in cognitive function while increasing connectivity in hippocampal circuitry. These data corroborate the extensive literature that drugs selectively targeting the AVP V1a receptor could be used to treat TBI in the clinic.
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Antagonistas de los Receptores de Hormonas Antidiuréticas/farmacología , Contusión Encefálica/diagnóstico por imagen , Edema Encefálico/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Cognición/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Contusión Encefálica/complicaciones , Contusión Encefálica/tratamiento farmacológico , Contusión Encefálica/fisiopatología , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/fisiopatología , Neuroimagen Funcional , Hipocampo/diagnóstico por imagen , Hipocampo/fisiopatología , Ventrículos Laterales/diagnóstico por imagen , Ventrículos Laterales/patología , Imagen por Resonancia Magnética , Aprendizaje por Laberinto , Tamaño de los Órganos , Ratas , Receptores de VasopresinasAsunto(s)
Velocidad del Flujo Sanguíneo , Edema Encefálico/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Fallo Renal Crónico/terapia , Arteria Cerebral Media/diagnóstico por imagen , Diálisis Renal/efectos adversos , Estado Epiléptico/fisiopatología , Resistencia Vascular , Anciano , Barrera Hematoencefálica/metabolismo , Contusión Encefálica/complicaciones , Contusión Encefálica/diagnóstico por imagen , Contusión Encefálica/metabolismo , Contusión Encefálica/fisiopatología , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Edema Encefálico/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/metabolismo , Hemorragia Cerebral Traumática/complicaciones , Hemorragia Cerebral Traumática/diagnóstico por imagen , Hemorragia Cerebral Traumática/metabolismo , Hemorragia Cerebral Traumática/fisiopatología , Trastornos de la Conciencia/etiología , Trastornos de la Conciencia/metabolismo , Trastornos de la Conciencia/fisiopatología , Cefalea/etiología , Cefalea/metabolismo , Cefalea/fisiopatología , Hematoma Subdural Agudo/complicaciones , Hematoma Subdural Agudo/diagnóstico por imagen , Hematoma Subdural Agudo/metabolismo , Hematoma Subdural Agudo/fisiopatología , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Masculino , Arteria Cerebral Media/fisiopatología , Monitoreo Fisiológico , Náusea/etiología , Náusea/metabolismo , Náusea/fisiopatología , Flujo Pulsátil , Estado Epiléptico/etiología , Estado Epiléptico/metabolismo , Ultrasonografía Doppler Transcraneal , Vómitos/etiología , Vómitos/metabolismo , Vómitos/fisiopatologíaRESUMEN
BACKGROUND: Measuring optic nerve sheath diameter (ONSD), an indicator to predict intracranial hypertension, is noninvasive and convenient, but the reliability of ONSD needs to be improved. Instead of using ONSD alone, this study aimed to evaluate the reliability of the ratio of ONSD to eyeball transverse diameter (ONSD/ETD) in predicting intracranial hypertension in traumatic brain injury (TBI) patients. METHODS: We performed a prospective study on patients admitted to the Surgery Intensive Care Unit. The included 52 adults underwent craniotomy for TBI between March 2017 and September 2018. The ONSD and ETD of each eyeball were measured by ultrasound and computed tomography (CT) scan within 24 h after a fiber optic probe was placed into lateral ventricle. Intracranial pressure (ICP) > 20 mmHg was regarded as intracranial hypertension. The correlations between invasive ICP and ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and CT-ONSD were each analyzed separately. RESULTS: Ultrasound measurement was successfully performed in 94% (n = 49) of cases, and ultrasound and CT measurement were performed in 48% (n = 25) of cases. The correlation efficiencies between ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and ICP were 0.613, 0.498, and 0.688, respectively (P < 0.05). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the ultrasound-ONSD/ETD ratio and CT-ONSD/ETD ratio were 0.920 (95% CI 0.877-0.964) and 0.896 (95% CI 0.856-0.931), respectively. The corresponding threshold values were 0.25 (sensitivity of 90%, specificity of 82.3%) and 0.25 (sensitivity of 85.7%, specificity of 83.3%), respectively. CONCLUSION: The ratio of ONSD to ETD tested by ultrasound may be a reliable indicator for predicting intracranial hypertension in TBI patients.
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Lesiones Traumáticas del Encéfalo/fisiopatología , Ojo/diagnóstico por imagen , Hipertensión Intracraneal/diagnóstico por imagen , Nervio Óptico/diagnóstico por imagen , Adulto , Contusión Encefálica/complicaciones , Contusión Encefálica/fisiopatología , Lesiones Traumáticas del Encéfalo/complicaciones , Hemorragia Cerebral Traumática/complicaciones , Hemorragia Cerebral Traumática/fisiopatología , Ojo/patología , Femenino , Escala de Coma de Glasgow , Hematoma Epidural Craneal/complicaciones , Hematoma Epidural Craneal/fisiopatología , Hematoma Intracraneal Subdural/complicaciones , Hematoma Intracraneal Subdural/fisiopatología , Humanos , Hipertensión Intracraneal/diagnóstico , Hipertensión Intracraneal/etiología , Masculino , Persona de Mediana Edad , Nervio Óptico/patología , Técnicas de Cultivo de Órganos , Estudios Prospectivos , Reproducibilidad de los Resultados , Hemorragia Subaracnoidea Traumática/complicaciones , Hemorragia Subaracnoidea Traumática/fisiopatología , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Traumatic brain injury (TBI), a major cause of mortality and morbidity, affects 10 million people worldwide, with limited treatment options. We have previously shown that (-)-phenserine (Phen), an acetylcholinesterase inhibitor originally designed and tested in clinical phase III trials for Alzheimer's disease, can reduce neurodegeneration after TBI and reduce cognitive impairments induced by mild TBI. In this study, we used a mouse model of moderate to severe TBI by controlled cortical impact to assess the effects of Phen on post-trauma histochemical and behavioral changes. Animals were treated with Phen (2.5 mg/kg, IP, BID) for 5 days started on the day of injury and the effects were evaluated by behavioral and histological examinations at 1 and 2 weeks after injury. Phen significantly attenuated TBI-induced contusion volume, enlargement of the lateral ventricle, and behavioral impairments in motor asymmetry, sensorimotor functions, motor coordination, and balance functions. The morphology of microglia was shifted to an active from a resting form after TBI, and Phen dramatically reduced the ratio of activated to resting microglia, suggesting that Phen also mitigates neuroinflammation after TBI. While Phen has potent anti-acetylcholinesterase activity, its (+) isomer Posiphen shares many neuroprotective properties but is almost completely devoid of anti-acetylcholinesterase activity. We evaluated Posiphen at a similar dose to Phen and found similar mitigation in lateral ventricular size increase, motor asymmetry, motor coordination, and balance function, suggesting the improvement of these histological and behavioral tests by Phen treatment occur via pathways other than anti-acetylcholinesterase inhibition. However, the reduction of lesion size and improvement of sensorimotor function by Posiphen were much smaller than with equivalent doses of Phen. Taken together, these results show that post-injury treatment with Phen over 5 days significantly ameliorates severity of TBI. These data suggest a potential development of this compound for clinical use in TBI therapy.
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Conducta Animal/efectos de los fármacos , Contusión Encefálica , Fármacos Neuroprotectores/farmacología , Fisostigmina/análogos & derivados , Animales , Contusión Encefálica/tratamiento farmacológico , Contusión Encefálica/metabolismo , Contusión Encefálica/patología , Contusión Encefálica/fisiopatología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Inflamación/fisiopatología , Masculino , Ratones , Microglía/metabolismo , Microglía/patología , Fisostigmina/farmacología , Factores de TiempoRESUMEN
Cerebral contusion causes neurological dysfunction mediated in part by inflammatory responses to injury. B lymphocytes are dynamic regulators of the immune system that have not been systematically studied in traumatic brain injury (TBI). We showed previously that topically applied mature B cells have immunomodulatory properties and strongly promote tissue regeneration, including cutaneous nerve growth, in acute and chronic skin wounds. Using a mouse controlled cortical impact (CCI) model, we assessed a possible beneficial role of exogenously applied B cells on histopathological and functional outcome after TBI. Mice were injected intraparenchymally at the lesion site with 2 × 106 mature naïve syngeneic splenic B cells, then subjected to CCI. Control CCI mice received equal numbers of T cells or saline, and sham-injured mice (craniotomy only) were given B cells or saline. Sham-injured groups performed similarly in motor and learning tests. Injured mice administered B cells showed significantly improved post-injury rotarod, Y maze, and Morris water maze (MWM) performance compared with saline- or T-cell-treated CCI groups. Moreover, lesion volume in mice treated with B cells was significantly reduced by 40% at 35 days post-TBI compared with saline and T cell controls, and astrogliosis and microglial activation were decreased. In vivo tracking of exogenous B cells showed that they have a limited life span of approximately 14 days in situ and do not appear to proliferate. The data suggest proof of principle that local administration of B lymphocytes may represent a therapeutic option for treatment of cerebral contusion, especially when clinical management involves procedures that allow access to the injury site.
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Linfocitos B/trasplante , Contusión Encefálica/patología , Contusión Encefálica/fisiopatología , Recuperación de la Función/fisiología , Animales , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Spreading depolarizations (SDs) occur in 50-60% of patients after surgical treatment of severe traumatic brain injury (TBI) and are independently associated with unfavorable outcomes. Here we performed a pilot study to examine the relationship between SDs and various types of intracranial lesions, progression of parenchymal damage, and outcomes. METHODS: In a multicenter study, fifty patients (76% male; median age 40) were monitored for SD by continuous electrocorticography (ECoG; median duration 79 h) following surgical treatment of severe TBI. Volumes of hemorrhage and parenchymal damage were estimated using unbiased stereologic assessment of preoperative, postoperative, and post-ECoG serial computed tomography (CT) studies. Neurologic outcomes were assessed at 6 months by the Glasgow Outcome Scale-Extended. RESULTS: Preoperative volumes of subdural and subarachnoid hemorrhage, but not parenchymal damage, were significantly associated with the occurrence of SDs (P's < 0.05). Parenchymal damage increased significantly (median 34 ml [Interquartile range (IQR) - 2, 74]) over 7 (5, 8) days from preoperative to post-ECoG CT studies. Patients with and without SDs did not differ in extent of parenchymal damage increase [47 ml (3, 101) vs. 30 ml (- 2, 50), P = 0.27], but those exhibiting the isoelectric subtype of SDs had greater initial parenchymal damage and greater increases than other patients (P's < 0.05). Patients with temporal clusters of SDs (≥ 3 in 2 h; n = 10 patients), which included those with isoelectric SDs, had worse outcomes than those without clusters (P = 0.03), and parenchymal damage expansion also correlated with worse outcomes (P = 0.01). In multivariate regression with imputation, both clusters and lesion expansion were significant outcome predictors. CONCLUSIONS: These results suggest that subarachnoid and subdural blood are important primary injury factors in provoking SDs and that clustered SDs and parenchymal lesion expansion contribute independently to worse patient outcomes. These results warrant future prospective studies using detailed quantification of TBI lesion types to better understand the relationship between anatomic and physiologic measures of secondary injury.
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Contusión Encefálica/patología , Contusión Encefálica/fisiopatología , Depresión de Propagación Cortical/fisiología , Hematoma Subdural Agudo/patología , Hematoma Subdural Agudo/fisiopatología , Hemorragia Subaracnoidea Traumática/patología , Hemorragia Subaracnoidea Traumática/fisiopatología , Adulto , Contusión Encefálica/diagnóstico por imagen , Electrocorticografía , Femenino , Estudios de Seguimiento , Escala de Consecuencias de Glasgow , Hematoma Subdural Agudo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Índice de Severidad de la Enfermedad , Hemorragia Subaracnoidea Traumática/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
We examined benzyl quinolone carboxylic acid (BQCA), a novel M1 muscarinic-positive allosteric modulator, for improving memory and motor dysfunction after cerebral cortical contusion injury (CCI). Adult mice received unilateral motorsensory cortical CCI or sham injury. Benzyl quinolone carboxylic acid (BQCA; 5, 10, and 20 mg/kg, intraperitoneally [i.p.] × 2/day × 3-4 weeks) or vehicle (Veh) were administered, and weekly evaluations were undertaken using a battery of motor tests, as well as the Morris water maze. Thereafter, cerebral metabolic activation was investigated in awake animals during walking with [14C]-2-deoxygIucose autoradiography, comparing CCI mice previously treated with BQCA (20 mg/kg) or vehicle. Relative changes in local cerebral glucose uptake (rCGU) were evaluated in three-dimensional-reconstructed brains using statistical parametric mapping. CCI resulted in mild hyperactivity in the open field, and modest significant motor deficits, as well as significantly decreased spatial learning at 3 weeks. BQCA in CCI mice resulted in significantly improved spatial recall during the third week, with minimal effects on motor outcomes. CCI significantly decreased rCGU in the ipsilesional basal ganglia-thalamocortical circuit and in somatosensory regions, with relative increases noted contralaterally, as well as in the cerebellum. Significant decreases in rCGU were noted in subregions of the ipsilesional hippocampal formation, with significant increases noted contralesionally. BQCA compared to vehicle-treated mice showed modest, though significantly increased, rCGU in motor regions, as well as a partial reversal of lesion-related rCGU findings in subregions of the hippocampal formation. rCGU in ipsilesional posterior CA1 demonstrated a significant inverse correlation with latency to find the submerged platform. BQCA at 20 mg/kg had no significant effect on general motor activity, body weight, or acute motor, secretory, or respiratory symptoms. Results suggest that BQCA is a candidate compound to improve learning and memory function after brain trauma and may not suffer the associated central nervous system side effects typically associated with even modest doses of other cholinergic enhancers.
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Contusión Encefálica/fisiopatología , Encéfalo/efectos de los fármacos , Quinolinas/farmacología , Recuperación de la Función/efectos de los fármacos , Aprendizaje Espacial/efectos de los fármacos , Animales , Agonistas Colinérgicos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.
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Contusión Encefálica/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Carnitina/administración & dosificación , Exenatida/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Contusión Encefálica/metabolismo , Contusión Encefálica/fisiopatología , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To investigate clinical efficacy of and optimal therapeutic strategy for ventricular intracranial pressure monitoring (V-ICPM) in patients with traumatic bifrontal contusions (TBCs). METHODS: From 8760 patients with traumatic brain injury treated between January 2010 and January 2016, a retrospective analysis was performed on 105 patients with TBCs who underwent V-ICPM and 282 patients with TBCs who did not. All patients underwent treatment at the 101st Hospital of PLA, Wuxi, China. Rates of successful conservative treatment, decompressive craniectomy, and bifrontal craniotomy; incidence of neurologic dysfunction; length of stay; and medical expenses were compared between groups. RESULTS: Glasgow Outcome Scale was used to assess all patients during follow-up (range, 6 months to 5.5 years). There were no significant differences in prognosis between the 2 groups (P = 0.100). Compared with the patients who did not undergo V-ICPM, the V-ICPM group had a significantly better successful conservative treatment rate (64.8% vs. 47.2%, P = 0.002), decompressive craniectomy rate (8.1% vs. 22.1%, P = 0.008), and bifrontal craniotomy rate (5.7% vs. 15.6%, P = 0.01); shorter length of stay (P = 0.000); and lower medical expenses (P = 0.004). CONCLUSIONS: Patients with TBCs should be strictly, closely, and dynamically observed by neurosurgery intensive care unit physicians and nurses. Patients should undergo ventricular intracranial pressure probe implantation in a timely manner. V-ICPM can help optimize treatment. Although V-ICPM did not significantly improve the prognosis of patients, it had many other advantages. V-ICPM warrants further clinical research and may be beneficial for patients with TBCs.
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Contusión Encefálica/diagnóstico por imagen , Contusión Encefálica/cirugía , Ventrículos Cerebrales/diagnóstico por imagen , Ventrículos Cerebrales/cirugía , Presión Intracraneal/fisiología , Monitorización Neurofisiológica Intraoperatoria/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Contusión Encefálica/fisiopatología , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/cirugía , Ventrículos Cerebrales/fisiopatología , Niño , Craniectomía Descompresiva/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: We aimed to investigate the prevalence and pattern of cognitive dysfunction in patients with traumatic bifrontal contusions and their association with functional outcome. MATERIALS AND METHODS: We prospectively recruited patients with bifrontal contusions in a regional neurosurgical center in Hong Kong over a 2-year period. Functional outcome was assessed by modified Rankin Scale (mRS), and cognitive outcomes were assessed by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a comprehensive neuropsychological battery. RESULTS: We recruited 34 patients with traumatic bifrontal contusions over a 2-year period. Nine (26%) patients had craniotomy for evacuation of left or right frontal contusions. Functional outcome using mRS was significantly correlated with cognitive outcomes using MMSE or MoCA. The effect of cognitive outcome using MMSE or MoCA persisted after adjustments of age, sex, admission Glasgow Coma Scale, and surgery. In patients who completed the comprehensive neuropsychological assessments, cognitive impairment in at least one of the neuropsychological tests was noted in 73% of them. CONCLUSIONS: Cognitive dysfunction had a significant impact on functional outcome, and treatment strategy should be developed to minimize them.
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Contusión Encefálica/psicología , Cognición , Disfunción Cognitiva/psicología , Lóbulo Frontal/lesiones , Adulto , Anciano , Contusión Encefálica/complicaciones , Contusión Encefálica/fisiopatología , Contusión Encefálica/cirugía , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Femenino , Lateralidad Funcional , Escala de Coma de Glasgow , Hong Kong , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
BACKGROUND: The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is a well-known entity. Consequently, the aim of the present study was to evaluate the role of omeprazole (OM) on rat model of TBI. METHODS: A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, OM, and methylprednisolone (MP). The trauma, OM, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with saline, OM, or MP, respectively. All the animals were sacrificed at 24 hours after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, nitric oxide) and caspase-3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. RESULTS: Levels of MDA and activity of caspase-3 were significantly reduced in the OM and MP groups compared with the trauma group. Glutathione peroxidase and superoxide dismutase levels were increased both in the OM and MP groups compared with the trauma group. The pathology scores were statistically lower in the OM and MP groups than the trauma group. CONCLUSIONS: The results of the present study showed that OM was as effective as MP in protecting brain from oxidative stress, and apoptosis in the early phase of TBI.
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Contusión Encefálica/prevención & control , Modelos Animales de Enfermedad , Omeprazol/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Contusión Encefálica/patología , Contusión Encefálica/fisiopatología , Masculino , Metilprednisolona/farmacología , Estrés Oxidativo/fisiología , RatasRESUMEN
BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1) regulates many processes after traumatic brain injury (TBI). Both Neuro AiD™ (MLC601) and astragaloside (AST) attenuate microglia activation in rats with TBI. The purpose of this study was to investigate whether MLC601 or AST improves output of TBI by affecting microglial expression of TGF-ß1. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (120 in number) were used to investigate the contribution of TGF-ß1-containing microglia in the MLC601-mediated or the AST-mediated neuroprotection in the brain trauma condition using lateral fluid percussion injury. RESULTS: Pearson correlation analysis revealed that there was a positive correlation between brain injury (evidenced by both brain contused volume and neurological severity score) and the cortical numbers of TGF-ß1-containing microglia for the rats (n = 12) 4 days post-TBI. MLC601 or AST significantly (P < 0·05) attenuated TBI-induced brain contused volume (119 ± 14 mm3 or 108 ± 11 mm3 vs. 160 ± 21 mm3 ), neurological severity score (7·8 ± 0·3 or 8·1 ± 0·4 vs. 10·2 ± 0·5) and numbers of TGF-ß1-containing microglia (6% ± 2% or 11% ± 3% vs. 79% ± 7%) for the rats 4 days post-TBI. CONCLUSIONS: There was a positive correlation between TBI and cortical numbers of TGF-ß1-containing microglia which could be significantly attenuated by astragaloside or NeuroAiD™ (MLC601) in rats.