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1.
Sci Rep ; 11(1): 20283, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645889

RESUMO

In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation-suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble-Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.


Assuntos
Fibrinólise , Traumatismos Cranianos Fechados/sangue , Traumatismos Cranianos Fechados/fisiopatologia , Animais , Gasometria , Transfusão de Sangue , Masculino , Plasma , Inibidor 1 de Ativador de Plasminogênio/sangue , Ratos , Ratos Wistar , Fatores de Tempo , Ativador de Plasminogênio Tecidual/biossíntese , Ferimentos não Penetrantes
2.
World Neurosurg ; 147: 172-180.e1, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33346052

RESUMO

BACKGROUND: Data on neuroendocrine dysfunction (NED) in the acute setting of penetrating brain injury (PBI) are scarce, and the clinical approach to diagnosis and treatment remains extrapolated from the literature on blunt head trauma. METHODS: Three databases were searched (PubMed, Scopus, and Cochrane). Risk of bias was computed using the Newcastle-Ottawa Scale, or the methodological quality of case series and case reports, as indicated. This systematic review was registered in PROSPERO (42020172163). RESULTS: Six relevant studies involving 58 patients with PBI were included. Two studies were prospective cohort analyses, whereas 4 were case reports. The onset of NED was acute in all studies, by the first postinjury day. Risk factors for NED included worse injury severity and the presence of cerebral edema on imaging. Dysfunction of the anterior hypophysis involved the hypothalamic-pituitary-thyroid axis, treated with hormonal replacement, and hypocortisolism, treated with hydrocortisone. The prevalence of central diabetes insipidus was up to 41%. Most patients showed persistent NED months after injury. In separate reports, diabetes insipidus and hypocortisolism showed an association with higher mortality. The available literature for this review is poor, and the studies included had overall low quality with high risk of bias. CONCLUSIONS: NED seems to be prevalent in the acute phase of PBI, equally involving both anterior and posterior hypophysis. Despite a potential association between NED and mortality, data on the optimal management of NED are limited. This situation defines the need for prospective studies to better characterize the clinical features and optimal therapeutic interventions for NED in PBI.


Assuntos
Insuficiência Adrenal/epidemiologia , Lesões Encefálicas/epidemiologia , Diabetes Insípido Neurogênico/epidemiologia , Traumatismos Cranianos Penetrantes/epidemiologia , Hipopituitarismo/epidemiologia , Hipotireoidismo/epidemiologia , Doença Aguda , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/fisiopatologia , Edema Encefálico , Lesões Encefálicas/fisiopatologia , Diabetes Insípido Neurogênico/tratamento farmacológico , Diabetes Insípido Neurogênico/fisiopatologia , Traumatismos Cranianos Fechados/epidemiologia , Traumatismos Cranianos Fechados/fisiopatologia , Traumatismos Cranianos Penetrantes/fisiopatologia , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/fisiopatologia , Sistema Hipotálamo-Hipofisário , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/fisiopatologia , Escala de Gravidade do Ferimento , Mortalidade , Sistema Hipófise-Suprarrenal , Prevalência , Prognóstico , Glândula Tireoide
3.
J Neurotrauma ; 37(24): 2664-2673, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32799741

RESUMO

Research suggests cumulative effects of repetitive head impacts (RHIs) on brain structure, especially with younger age of first exposure. Further, recent evidence suggests no immediate cognitive changes with increased RHIs but impairments across a sports season. The aim was to examine more closely the short-term time course of behavioral effects of exposure to RHI. Across 2 years, 18 female adolescent soccer players were tested on ProPoint (sensorimotor) and AntiPoint (cognitive) tasks with reaction time (RT) being the main outcome measure. The athletes were tested before and after workout with ball heading (immediate effect), as well as 24 h after workout (24 h effect) throughout two consecutive seasons. The number of headers performed 24 h before workout, during workout, and season average per workout were recorded. The athletes showed a decrease in ProPoint and AntiPoint RTs immediately after a workout, with no change or decrease in RTs with increasing RHIs. However, increasing RHIs during workout increased RTs in both tasks when tested 24 h later. The athletes also showed an increase in AntiPoint RTs with increasing season average RHIs. Our findings show a complex time course of effects of RHIs on sensorimotor and cognitive performance in adolescent athletes, with exposure to RHIs associated with no change or immediate benefits and then deficits by 24 h. Pathophysiological changes associated with exercise and traumatic brain injury can account for the sensorimotor and cognitive performance changes occurring within 24 h after RHIs.


Assuntos
Atletas , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/fisiopatologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Futebol/lesões , Adolescente , Feminino , Humanos
4.
J Neurotrauma ; 37(24): 2656-2663, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32571175

RESUMO

The purpose of this study was to compare sensory reweighting for upright stance between soccer players who report higher soccer heading exposure to those who report lower soccer heading exposure. Thirty participants completed a self-reported questionnaire to estimate the number of soccer headers experienced over the previous year and were divided into "low exposure" and "high exposure" groups based on their responses. Sensory reweighting for upright stance was assessed by simultaneously perturbing visual, vestibular, and proprioceptive systems. The visual stimulus was a sinusoidal translation of the visual scene at 0.2 Hz, the vestibular stimulus was ±1mA binaural monopolar galvanic vestibular stimulation (GVS) at 0.36 Hz, and the proprioceptive stimulus was Achilles tendon vibration at 0.28 Hz. The visual stimulus was presented at two amplitudes (0.2 m, 0.8 m). Center of mass (COM) gain/phase to each modality, total power, 95% area and velocity were compared between low exposure (N = 15, six males, 21.5 ± 1.9 years, 27.7 ± 31.6 headers) and high exposure groups (N = 15, 10 males, 22.1 ± 3.5years, 734.9 ± 877.7 headers). Without vibration, COM 95% area (F = 5.861, p = 0.022*, partial η2 = 0.173), velocity (F = 14.198, p = 0.001, partial η2 = 0.336), and total power (F = 13.491, p = 0.001, partial η2 = 0.325) for the "high exposure" group were higher than for the "low exposure" group, and postural sway lagged the vestibular stimulus in the "high exposure" group rather than leading it as in the "low exposure" group (F = 4.765, p = 0.038, partial η2 = 0.145). There were no differences in sensory reweighting and no differences in COM gain/phase between groups. These findings lend empirical evidence to a detrimental effect of soccer heading exposure on balance control during upright stance.


Assuntos
Traumatismos Cranianos Fechados/fisiopatologia , Equilíbrio Postural/fisiologia , Futebol/lesões , Adolescente , Adulto , Feminino , Traumatismos Cranianos Fechados/etiologia , Humanos , Masculino , Adulto Jovem
5.
Res Sports Med ; 28(1): 55-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30880469

RESUMO

While many research efforts have focused on head impact exposure in professional soccer, there have been few studies characterizing exposure at the youth level. The aim of this study is to evaluate a new instrumentation approach and collect some of the first head impact exposure data for youth female soccer players. Athletes were instrumented with custom-fit mouthpieces that measure head impacts. Detailed video analysis was conducted to identify characteristics describing impact source (e.g., kick, header, throw). A total of 763 verified head impacts were collected over 23 practices and 8 games from 7 athletes. The median peak linear accelerations, rotational velocities, and rotational accelerations of all impacts were 9.4 g, 4.1 rad/s, and 689 rad/s2, respectively. Pairwise comparisons resulted in statistically significant differences in kinematics by impact source. Headers following a kicked ball had the highest accelerations and velocity when compared to headers from thrown or another header.


Assuntos
Traumatismos em Atletas/fisiopatologia , Traumatismos Cranianos Fechados/fisiopatologia , Protetores Bucais , Futebol/lesões , Adolescente , Fenômenos Biomecânicos , Criança , Feminino , Humanos
6.
Forensic Sci Int ; 306: 110060, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785511

RESUMO

In order to investigate potential causal relations between the shaking of infants and injuries, biomechanical studies compare brain and skull dynamic behavior during shaking to injury thresholds. However, performing shaking tolerance research on infants, either in vivo or ex vivo, is extremely difficult, if not impossible. Therefore, infant injury thresholds are usually estimated by scaling or extrapolating adult or animal data obtained from crash tests or whiplash experiments. However, it is doubtful whether such data accurately matches the biomechanics of shaking in an infant. Hence some thresholds may be inappropriate to be used for the assessment of inflicted head injury by shaking trauma in infants. A systematic literature review was conducted to 1) provide an overview of existing thresholds for head- and neck injuries related to violent shaking, and 2) to identify and discuss which thresholds have been used or could be used for the assessment of inflicted head injury by shaking trauma in infants. Key findings: The majority of studies establishing or proposing injury thresholds were found to be based on loading cycle durations and loading cycle repetitions that did not resemble those occurring during shaking, or had experimental conditions that were insufficiently documented in order to evaluate the applicability of such thresholds. Injury thresholds that were applied in studies aimed at assessing whether an injury could occur under certain shaking conditions were all based on experiments that did not properly replicate the loading characteristics of shaking. Somewhat validated threshold scaling methods only exist for scaling concussive injury thresholds from adult primate to adult human. Scaling methods that have been used for scaling other injuries, or for scaling adult injury thresholds to infants were not validated. There is a clear and urgent need for new injury thresholds established by accurately replicating the loading characteristics of shaking.


Assuntos
Fenômenos Biomecânicos/fisiologia , Síndrome do Bebê Sacudido/fisiopatologia , Aceleração , Animais , Lesão Axonal Difusa/fisiopatologia , Medicina Legal/métodos , Traumatismos Cranianos Fechados/fisiopatologia , Humanos , Lactente , Hemorragias Intracranianas/fisiopatologia , Modelos Biológicos , Lesões do Pescoço/fisiopatologia , Hemorragia Retiniana/fisiopatologia
7.
Clin Biomech (Bristol, Avon) ; 67: 96-101, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31082637

RESUMO

BACKGROUND: Loss of consciousness is a poorly understood indicator of concussion severity. Conflicting results have been published supporting loss of consciousness as a severe concussion as well as having no relationship with severity. Understanding how loss of consciousness relates to brain trauma severity will provide useful insights to guide rule changes and return to sport protocols. The purpose of this study was to compare magnitudes of head acceleration and brain tissue deformation for punches resulting in a loss of consciousness and punches that do not. METHODS: Physical representations of boxing punches presenting with and without loss of consciousness were performed using an anthropometric headform and finite element model. The variables measured were peak linear and rotational acceleration, maximum principal strain, cumulative strain damage 10%, and strain rate in five regions of the brain. FINDINGS: Loss of consciousness in boxing resulted from hooks to the side of the mandible creating high levels of rotational acceleration and increased magnitudes of brain trauma in all regions of the brain. Differences between punches resulting in loss of consciousness and no loss of consciousness were distinguished by maximum principal strain for each of the brain region analyzed. INTERPRETATION: This research supports the notion that loss of consciousness in boxing is caused by higher levels of brain trauma and may require a longer recovery time.


Assuntos
Traumatismos em Atletas/fisiopatologia , Boxe/lesões , Concussão Encefálica/fisiopatologia , Traumatismos Cranianos Fechados/fisiopatologia , Cabeça/fisiopatologia , Inconsciência/fisiopatologia , Aceleração , Algoritmos , Antropometria , Fenômenos Biomecânicos , Encéfalo/patologia , Humanos , Modelos Lineares , Masculino , Gravação em Vídeo
8.
J Neurotrauma ; 36(14): 2260-2271, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30843474

RESUMO

Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research.


Assuntos
Concussão Encefálica/fisiopatologia , Modelos Animais de Doenças , Neuroglia , Animais , Estado de Consciência , Comportamento Exploratório , Traumatismos Cranianos Fechados/fisiopatologia , Masculino , Aprendizagem em Labirinto , Ratos , Ratos Long-Evans
9.
Int J Numer Method Biomed Eng ; 35(5): e3187, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30861631

RESUMO

Shear shock waves can be generated spontaneously deep within the brain during a traumatic injury. This recently observed behavior could be a primary mechanism for the generation of traumatic brain injuries. However, shear shock wave physics and its numerical modeling are relatively unstudied. Existing numerical solvers used in biomechanics are not designed for the extremely large Mach numbers (greater than 1) observed in the brain. Furthermore, soft solids, such as the brain, have a complex nonclassical viscoleastic response, which must be accurately modeled to capture the nonlinear wave behavior. Here, we develop a 1D inviscid velocity-stress-like system to model the propagation of shear shock waves in a homogeneous medium. Then a generalized Maxwell body is used to model a relaxing medium that can describe experimentally determined attenuation laws. Finally, the resulting system is solved numerically with the piecewise parabolic method, a high-order finite volume method. The nonlinear and the relaxing components of this method are validated with theoretical predictions. Comparisons between numerical solutions obtained for the proposed model and the experiments of plane shear shock wave propagation based on high frame-rate ultrasound imaging and tracking are shown to be in excellent agreement.


Assuntos
Encéfalo/fisiologia , Traumatismos Cranianos Fechados/fisiopatologia , Modelos Biológicos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Análise de Elementos Finitos , Humanos , Dinâmica não Linear , Reprodutibilidade dos Testes , Ultrassonografia
10.
Forensic Sci Med Pathol ; 15(3): 423-436, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30784025

RESUMO

Various types of complex biomechanical models have been published in the literature to better understand processes related to inflicted head injury by shaking trauma (IHI-ST) in infants. In this systematic review, a comprehensive overview of these models is provided. A systematic review was performed in MEDLINE and Scopus for articles using physical (e.g. dolls) and mathematical (e.g. computer simulations) biomechanical models for IHI-ST. After deduplication, the studies were independently screened by two researchers using PRISMA methodology and data extracted from the papers is represented in a "7-steps description", addressing the different processes occurring during IHI-ST. Eleven papers on physical models and 23 papers on mathematical models were included after the selection process. In both categories, some models focus on describing gross head kinematics during IHI-ST events, while others address the behavior of internal head- and eye structures in various levels of detail. In virtually all physical and mathematical models analyzed, injury thresholds are derived from scaled non-infant data. Studies focusing on head kinematics often use injury thresholds derived from impact studies. It remains unclear to what extent these thresholds reflect the failure thresholds of infant biological material. Future research should therefore focus on investigating failure thresholds of infant biological material as well as on possible alternative injury mechanism and alternative injury criteria for IHI-ST.


Assuntos
Fenômenos Biomecânicos/fisiologia , Simulação por Computador , Traumatismos Cranianos Fechados/fisiopatologia , Modelos Biológicos , Síndrome do Bebê Sacudido/fisiopatologia , Criança , Maus-Tratos Infantis , Humanos , Modelos Teóricos
11.
Comput Methods Biomech Biomed Engin ; 22(3): 229-242, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30596531

RESUMO

Despite the progress in developing personal combat-protective gear, eye and brain injuries are still widely common and carry fatal or long-term repercussions. The complex nature of the cranial tissues suggests that simple methods (e.g. crash-dummies) for testing the effectiveness of personal protective gear against non-penetrating impacts are both expensive and ineffective, and there are ethical issues in using animal or cadavers. The present work presents a versatile testing framework for quantitatively evaluating protective performances of head and eye combat-protective gear, against non-penetrating impacts. The biomimetic finite element (FE) head model that was developed provides realistic representation of cranial structure and tissue properties. Simulated crash impact results were validated against a former cadaveric study and by using a crash-phantom developed in our lab. The model was then fitted with various helmet and goggle designs onto which a non-penetrating ballistic impact was applied. Example data show that reduction of the elastic and shear moduli by 30% and 80% respectively of the helmet outer Kevlar-29 layer, lowered intracranial pressures by 20%. Our modeling suggests that the level of stresses that develop in brain tissues, which ultimately cause the brain damage, cannot be predicted solely by the properties of the helmet/goggle materials. We further found that a reduced contact area between goggles and face is a key factor in reducing the mechanical loads transmitted to the optic nerve and eye balls following an impact. Overall, this work demonstrates the simplicity, flexibility and usefulness for development, evaluation, and testing of combat-protective equipment using computational modeling. Highlights A finite element head model was developed for testing head gear. Reduced helmet's outer layer elastic and shear moduli lowered intracranial stresses. Gear material properties could not fully predict impact-related stress in the brain. Reduced goggles-face contact lowered transmitted loads to the optic nerve and eyes.


Assuntos
Dispositivos de Proteção dos Olhos , Traumatismos Cranianos Fechados/patologia , Dispositivos de Proteção da Cabeça , Animais , Fenômenos Biomecânicos , Encéfalo/patologia , Encéfalo/fisiopatologia , Simulação por Computador , Análise de Elementos Finitos , Traumatismos Cranianos Fechados/fisiopatologia , Humanos , Pressão Intracraniana , Imagens de Fantasmas , Pressão , Reprodutibilidade dos Testes
12.
Comput Methods Biomech Biomed Engin ; 22(2): 169-179, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30582366

RESUMO

To better understand head injuries, human head finite element (FE) models have been reported in the literature. In scenarios where the head is directly impacted and measurements of head accelerations are not available, a high-quality skull model, as well as a high-quality brain model, is needed to predict the effect of impact on the brain through the skull. Furthermore, predicting cranial bone fractures requires comprehensively validated skull models. Lastly, high-quality meshes for both the skull and brain are needed for accurate strain/stress predictions across the entire head. Hence, we adopted a multi-block approach to develop hexahedral meshes for the brain, skull, and scalp simultaneously, a first approach in its kind. We then validated our model against experimental data of brain pressures (Nahum et al., 1977 ) and comprehensive skull responses (Yoganandan et al., 1995 , Yoganandan et al., 2004 , and Raymond et al., 2009 ). We concluded that a human head FE model was developed with capabilities to predict blunt- and ballistic-impact-induced skull fractures and pressure-related brain injuries.


Assuntos
Encéfalo/fisiologia , Análise de Elementos Finitos , Pressão , Crânio/fisiologia , Adulto , Fenômenos Biomecânicos , Cabeça/fisiologia , Traumatismos Cranianos Fechados/fisiopatologia , Humanos , Masculino , Modelos Biológicos , Reprodutibilidade dos Testes , Fraturas Cranianas/fisiopatologia
13.
J Neurotrauma ; 36(10): 1655-1669, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30526351

RESUMO

Concussive traumatic brain injury (TBI) is the predominant type of brain injury in young adults and is a risk factor for the development of chronic traumatic encephalopathy and other neurodegenerative diseases late in life. Using a repetitive closed head injury mouse model, we found that treatment with PF04457845, a novel fatty acid amide hydrolase (FAAH) inhibitor that selectively elevated the brain levels of anandamide, improved locomotor function, learning, and memory in TBI mice examined by beam walk, Y-maze, and Morris water maze tests. The accumulation of microglia and astrocytes and the expression of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α), in the ipsilateral TBI mouse cortex and hippocampus were significantly reduced by drug treatment. The increased expression of amyloid precursor protein (APP), phosphorylated Tau (p-Tau), phosphorylated glycogen synthase kinase 3 beta (pGSK3ß) and p35/p25 subunits and the decreased expression of the pre-synaptic proteins, synaptophysin, synaptosome-associated protein of 25 kDa (SNAP25), and cysteine string protein alpha (α-CSP), in TBI mouse brain were also normalized by PF04458745 treatment. The improved locomotor function and working memory were partially mediated by activation of both cannabinoid (CB)1 and CB2 receptors, whereas the improvement on spatial learning and memory seemed to be CB1 receptor dependent. Interestingly, the blockage of PF04457845 on the reduced expression of synaptophysin, but not SNAP25 and α-CSP, was reversed by coadministration of the CB1 receptor antagonist. These results suggest that the therapeutic effect of PF04457845 is mediated by both cannabinoid receptor dependent and independent mechanisms, and selective inhibition of FAAH possesses a great potential for the treatment of TBI.


Assuntos
Concussão Encefálica , Encéfalo/efeitos dos fármacos , Traumatismos Cranianos Fechados , Fármacos Neuroprotetores/farmacologia , Piridazinas/farmacologia , Ureia/análogos & derivados , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Concussão Encefálica/etiologia , Concussão Encefálica/patologia , Concussão Encefálica/fisiopatologia , Modelos Animais de Doenças , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/patologia , Traumatismos Cranianos Fechados/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ureia/farmacologia
14.
Neurorehabil Neural Repair ; 33(1): 15-26, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30499355

RESUMO

BACKGROUND: Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that cerebrolysin significantly improves functional recovery in rats after mild traumatic brain injury (mTBI). OBJECTIVE: To determine histological outcomes associated with therapeutic effects of cerebrolysin on functional recovery after TBI. METHODS: In this prospective, randomized, blinded, and placebo-controlled study, adult Wistar rats with mild TBI induced by a closed head impact were randomly assigned to one of the cerebrolysin dose groups (0.8, 2.5, 7.5 mL/kg) or placebo, which were administered 4 hours after TBI and then daily for 10 consecutive days. Functional tests assessed cognitive, behavioral, motor, and neurological performance. Study end point was day 90 after TBI. Brains were processed for histological tissue analyses of astrogliosis, axonal injury, and neurogenesis. RESULTS: Compared with placebo, cerebrolysin significantly reduced amyloid precursor protein accumulation, astrogliosis, and axonal damage in various brain regions and increased the number of neuroblasts and neurogenesis in the dentate gyrus. There was a significant dose effect of cerebrolysin on functional outcomes at 3 months after injury compared with saline treatment. Cerebrolysin at a dose of ⩾0.8 mL/kg significantly improved cognitive function, whereas at a dose of ⩾2.5 mL/kg, cerebrolysin also significantly improved sensorimotor function at various time points. There were significant correlations between multiple histological and functional outcomes 90 days after mTBI. CONCLUSIONS: Our findings demonstrate that cerebrolysin reduces astrogliosis and axonal injury and promotes neurogenesis, which may contribute to improved functional recovery in rats with mTBI.


Assuntos
Aminoácidos , Concussão Encefálica , Traumatismos Cranianos Fechados , Fármacos Neuroprotetores , Animais , Masculino , Ratos , Aminoácidos/administração & dosagem , Aminoácidos/farmacologia , Concussão Encefálica/tratamento farmacológico , Concussão Encefálica/etiologia , Concussão Encefálica/patologia , Concussão Encefálica/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/tratamento farmacológico , Traumatismos Cranianos Fechados/patologia , Traumatismos Cranianos Fechados/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Ratos Wistar
15.
JAMA Ophthalmol ; 137(3): 265-270, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30570665

RESUMO

Importance: Repetitive subconcussive head impacts in sports have emerged as a complex public health issue. Most of these head impacts remain asymptomatic yet have the potential to cause insidious neurological deficit if sustained repetitively. Near point of convergence (NPC) values have shown to reflect subclinical neuronal damage; however, the longitudinal pattern of NPC changes in association with subconcussive head impacts remains unclear. Objectives: To examine the NPC response to recurring subconcussive head impacts in a single high school football season through a series of repeated measurements. Design, Setting, and Participants: This prospective case-series study of US varsity high school football players included baseline measurements of NPC, measurements at pregame and postgame points from 6 in-season games, and postseason follow-up measurements (a total of 14 points). An accelerometer-embedded mouthguard measured head impact frequency and magnitude from all practices and games. During the 6 games, players wore chest-strap heart rate monitors to record heart rate and estimate their excess postexercise oxygen consumption, accounting for possible physical exertion effects on NPC values. Exposures: Players participated in practices and games with no restriction. Main Outcomes and Measures: Near point of convergence. Results: The 12 included players were all boys, with a mean (SD) age of 16.4 (0.5) years. A total of 8009 head impacts, 177 907 g of peak linear acceleration, and 16 123 371 rad/s2 of peak rotational acceleration were recorded from the players in a single football season. There was a significant increase in NPC over time until the middle of the season (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 3, 6.42 [1.93] cm; P = .01), which was significantly associated with subconcussive head impact frequency and magnitude (0.02 cm per 100 g of peak linear acceleration [SE, 0.0108; 95% CI, 0.0436-0.004]; P = .01; 0.023 cm per 10 000 rad/s2 of peak rotational acceleration [SE, 0.009; 95% CI, 0.041-0.0105]; P = .02). However, NPC values began to normalize toward baseline level from midseason (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 6, 5.75 [2.23] cm; P = .32), as supported by a significant quadratic trend (ß [SE], -0.002 [0.001] cm/d; P = .003), while participants continued to incur subconcussive head impacts. Conclusions and Relevance: This longitudinal case series study suggests that NPC can be perturbed over the long term by subconcussive head impacts but may normalize over time. The oculomotor system may have an adaptational capacity to subclinical head impacts, yet the mechanism for such remains an open question and warrants further investigation.


Assuntos
Traumatismos em Atletas/fisiopatologia , Concussão Encefálica/fisiopatologia , Convergência Ocular/fisiologia , Futebol Americano/lesões , Traumatismos Cranianos Fechados/fisiopatologia , Adolescente , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos
16.
Brain Inj ; 33(2): 233-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30380944

RESUMO

OBJECTIVES: The long-term effects of concussion in youth remain poorly understood. The objective of this study was to determine the association between history of concussion and cerebral blood flow (CBF) in youth. METHODS: A total of 53 children and adolescents with a history of concussion (n = 37) or orthopaedic injury (OI; n = 16) were considered. Measures included pseudo-continuous arterial spin labelling magnetic resonance imaging to quantify CBF, post-concussion symptoms, psychological symptoms, and cognitive testing. RESULTS: Participants (mean age: 14.4 years, 95% CI = 13.8-15.4, range = 8-19) were on average 2.7 years (95% CI = 2.2-3.1) post-injury. Youth with a history of concussion had higher parent-reported physical, cognitive, anxiety, and depression symptoms than children with OI, but the groups did not differ on self-reported symptoms (post-concussive or psychological) or cognitive testing. Global CBF did not differ between groups. Regional CBF analyses suggested that youth with a history of concussion had hypoperfusion in posterior and inferior regions and hyperperfusion in anterior/frontal/temporal regions as compared to those with OI. However, neither global nor regional CBF were significantly associated with demographics, pre-injury functioning, number of concussions, time since injury, post-concussive symptoms, psychological symptoms, or cognitive abilities. CONCLUSIONS: Youth with a history of concussion demonstrate differences in regional CBF (not global CBF), but without clear clinical expression.


Assuntos
Concussão Encefálica/fisiopatologia , Circulação Cerebrovascular , Adolescente , Concussão Encefálica/diagnóstico por imagem , Criança , Feminino , Traumatismos Cranianos Fechados/diagnóstico por imagem , Traumatismos Cranianos Fechados/fisiopatologia , Traumatismos Cranianos Fechados/psicologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Perfusão , Síndrome Pós-Concussão/diagnóstico por imagem , Síndrome Pós-Concussão/fisiopatologia , Síndrome Pós-Concussão/psicologia , Recidiva , Marcadores de Spin , Adulto Jovem
17.
J Int Adv Otol ; 14(3): 347-352, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30541709

RESUMO

OBJECTIVES: The objective of the study was to assess the outcomes of cochlear implantation in patients deafened following blunt head trauma. MATERIAL AND METHODS: Retrospective case series review of seven patients post-lingually deafened following blunt head trauma and aided with cochlear implants. The following data were analyzed: Cause of injury, computed tomography results, surgical information, intra- and post-implantation complications, audiometric and speech perception assessment, processor mapping, and data from follow-up appointments. RESULTS: The median age of patients at the time of cochlear implantation was 29 years. The median time elapsed between head trauma and cochlear implantation was 5.77 months (minimum 0.8 and maximum 6.73 months). The median post-implantation follow-up time was 11.97 years. No facial nerve stimulation was observed in any case. All patients significantly improved their audiology and speech perception performances within a short time following cochlear implantation and CI performance did not decrease with long-term follow-up in any case. CONCLUSION: The results of this study showed that cochlear implantation is an effective treatment method for patients deafened following blunt head trauma.


Assuntos
Implante Coclear , Implantes Cocleares , Correção de Deficiência Auditiva/estatística & dados numéricos , Surdez/reabilitação , Traumatismos Cranianos Fechados/complicações , Adulto , Audiometria de Tons Puros , Correção de Deficiência Auditiva/métodos , Surdez/etiologia , Surdez/fisiopatologia , Feminino , Traumatismos Cranianos Fechados/fisiopatologia , Audição , Humanos , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Percepção da Fala , Resultado do Tratamento
18.
World Neurosurg ; 120: e667-e674, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30189306

RESUMO

BACKGROUND: Hypotension, a risk factor for increased mortality following traumatic brain injury (TBI), is traditionally defined as systolic blood pressure (SBP) <90 mm Hg. We aimed to redefine hypotension and determine its optimal threshold in patients with TBI. METHODS: We identified patients with severe TBI (Glasgow Coma Scale score ≤8 on admission) between 2004 and 2015 using data from the Japan Trauma Data Bank. Our endpoint was in-hospital mortality. Mixed effects logistic regression models were used to investigate the association between SBP on admission and in-hospital mortality, with hospitals considered as a random effects variable. We also conducted analyses stratified by age (≤60 years and >60 years) to determine age-specific optimal levels of SBP. RESULTS: A total of 12,537 patients (5665 patients ≤60 years old and 6872 patients >60 years old) were eligible for the analyses. Overall, SBP of 110 mm Hg was the optimal threshold for hypotension, and adjusted odds ratio and C-statistic for mortality at SBP <110 mm Hg on admission were 1.58 (95% confidence interval, 1.42-1.76, P < 0.001) and 0.78 (95% confidence interval, 0.77-0.79), respectively. Stratified analyses showed that optimal thresholds for hypotension in patients ≤60 years old and >60 years old were 100 mm Hg and 120 mm Hg. CONCLUSIONS: The threshold for hypotension in patients with severe TBI should be redefined and modified by age, and patients ≤60 years old should be considered hypotensive at SBP <100 mm Hg, whereas in older patients, SBP <120 mm Hg should be diagnosed as hypotension.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Hipotensão/diagnóstico , Hipotensão/fisiopatologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Traumatismos Cranianos Fechados/mortalidade , Traumatismos Cranianos Fechados/fisiopatologia , Mortalidade Hospitalar , Humanos , Hipotensão/mortalidade , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos
19.
J Trauma Nurs ; 25(5): 301-306, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30216260

RESUMO

Although clinical signs for the diagnosis of basilar skull fracture (BSF) are ambiguous, they are widely used to make decisions on initial interventions involving trauma patients. We aimed to assess the performance of early and late (within 48 hr posttrauma) signs for BSF diagnosis and to verify the correlation between the presence of these signs and head injury severity. We conducted a prospectively designed follow-up study at a referral hospital for trauma care in Sao Paulo, Brazil, and performed structured observations for 48 hr post-blunt head injury in patients aged 12 years or older. The following signs of BSF were considered: raccoon eyes, Battle's sign, otorrhea, and rhinorrhea. Among the 136 enrolled patients (85.3% male; mean age 40 ± 21.4 years), 28 patients (20.6%) had BSF. The clinical signs for the early or late detection of BSF had low accuracy (55.9% vs. 43.4%), specificity (52.8% vs. 30.5%), and positive predictive value (25.7% vs. 27.1%). However, the presence of these signs was correlated to head injury severity, indicated by the Glasgow Coma Scale (p = .041) and Maximum Abbreviated Injury Scale-Head region (p = .002). In view of the low accuracy of these signs, resulting low clinical value of their presence, and their high sensitivity in the late stage, the study results contraindicate the value of BSF signs for making decisions about using the nasal route for the introduction of catheters and tubes in initial trauma care.


Assuntos
Traumatismos Cranianos Fechados/diagnóstico por imagem , Traumatismos Cranianos Fechados/fisiopatologia , Mortalidade Hospitalar/tendências , Fratura da Base do Crânio/diagnóstico por imagem , Fratura da Base do Crânio/fisiopatologia , Adolescente , Adulto , Fatores Etários , Brasil , Criança , Tomada de Decisão Clínica , Estudos de Coortes , Serviço Hospitalar de Emergência , Tratamento de Emergência/métodos , Feminino , Escala de Coma de Glasgow , Traumatismos Cranianos Fechados/diagnóstico , Traumatismos Cranianos Fechados/mortalidade , Hospitais Universitários , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Fratura da Base do Crânio/diagnóstico , Fratura da Base do Crânio/mortalidade , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
20.
Brain Inj ; 32(12): 1549-1555, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30059631

RESUMO

BACKGROUND: Eye behaviour is important to distinguish minimally conscious state (MCS) from vegetative state (VS). OBJECTIVE: To search for conditions most suitable to characterize patients in MCS and in VS on quantitative assessment of visual tracking. DESIGN: This is a cross-sectional study. PARTICIPANTS: In total, 20 patients in VS, 13 in MCS plus and 11 in MCS minus participated in this study. SETTING: Neurorehabilitation Unit. METHODS: Evaluation of eye behaviour was performed by infrared system; stimuli were represented by a red circle, a picture of a patient's own face and a picture of an unfamiliar face, slowly moving on a personal computer (PC) monitor. Visual tracking on the horizontal and vertical axes was compared. MAIN OUTCOME MEASURES: The main outcome measures were proportion of on-target fixations and mean fixation duration. RESULTS: The proportion of on-target fixations differed as a function of the stimulus in patients in MCS plus but not in other groups. Own face and unfamiliar face elicited a similar proportion of on-target fixations. Tracking along the horizontal axis was more accurate than that along the vertical axis in patients in both MCS plus and MCS minus. Fixation duration did not differ among the three groups. CONCLUSIONS: Horizontal visual tracking of salient stimuli seems particularly suitable for eliciting on-target fixations. Quantitative assessment of visual tracking can complement clinical evaluation for reducing diagnostic uncertainty between patients in MCS or VS.


Assuntos
Transtornos da Consciência/diagnóstico , Movimentos Oculares/fisiologia , Traumatismos Cranianos Fechados/fisiopatologia , Hipóxia Encefálica/fisiopatologia , Exame Neurológico , Acidente Vascular Cerebral/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Transtornos da Consciência/fisiopatologia , Estudos Transversais , Estudos de Avaliação como Assunto , Potenciais Evocados Visuais/fisiologia , Feminino , Traumatismos Cranianos Fechados/complicações , Humanos , Hipóxia Encefálica/complicações , Masculino , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa , Valor Preditivo dos Testes , Acidente Vascular Cerebral/complicações , Adulto Jovem
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