Browsing by Subject "Traumatic brain injury"
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- PublicationRestrictedAtlanto-occipital dislocation with concomitant severe traumatic brain injury: a retrospective study at a level 1 trauma center(Elsevier, 2022-02-09) García Pérez, Daniel; Panero, Irene; Lagares, Alfonso; Gómez, Pedro Antonio; Alén, José F.; Paredes, Igor; FarmacologíaBackground Traumatic atlanto-occipital dislocation (AOD) is a life-threatening injury. Although traumatic brain injury (TBI) is associated with increased mortality in AOD patients, a detailed individual analysis of these patients is lacking in the literature. Methods Patients ≥16 years old who were diagnosed of AOD with concomitant severe TBI from 2010 to 2020 were included in this retrospective study. We examined the epidemiology, injury mechanisms, associated injuries, and outcomes of these patients. Results Eight patients were included. Six patients died before any intervention could be performed, and two patients underwent an occipito-cervical fixation, showing a notorious neurologic improvement on follow-up. Cardiorespiratory arrest (CRA) was a strong predictor of subsequent death. CT signs of diffuse axonal injury (DAI) were present in most patients and were confirmed by magnetic resonance imaging (MRI) in survivors. Although TBI was not the main cause of death, it was responsible for the delayed neurological improvement and deferred stabilization. The average sensitivity of the different used methodologies for AOD diagnosis ranged from 0.50 to 1.00, being the Basion Dens Interval (BDI) and the Condyle-C1 interval (CCI) sum the most reliable criteria. Non-survivors tended to show greater distraction measurements. The high incidence of condylar avulsion fractures suggests that their visualization on the initial CT study should heighten the suspicion for AOD. Conclusions Our data suggest that patients with AOD and concomitant severe TBI might be salvageable patients. In those who survive beyond the first hospital days and show neurological improvement, surgical treatment should be performed as they can achieve an important neurologic recovery.
- PublicationOpen AccessBlood-brain barrier disruption following brain injury: Implications for clinical practice(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Bai, Ruojing; Ge, XintongThe blood-brain barrier (BBB) plays a critical role in regulating the exchange of substances between peripheral blood and the central nervous system and in maintaining the stability of the neurovascular unit in neurological diseases. To guide clinical treatment and basic research on BBB protection following brain injury, this manuscript reviews how BBB disruption develops and influences neural recovery after stroke and traumatic brain injury (TBI). By summarizing the pathological mechanisms of BBB damage, we underscore the critical role of promoting BBB repair in managing brain injury. We also emphasize the potential for personalized and precise therapeutic strategies and the need for continued research and innovation. From this, broadening insights into the mechanisms of BBB disruption and repair could pave the way for breakthroughs in the treatment of brain injury-related diseases.
- PublicationRestrictedChitinase-3-Like Protein 1, Serum Amyloid A1, C-Reactive Protein, and Procalcitonin are promising biomarkers for intracranial severity assessment of traumatic brain injury: relationship with Glasgow Coma Scale and computed tomography volumetry(Elsevier, 2020-02-11) Sánchez Carabias, Cristina; Gómez, Pedro A.; Panero, Irene; Castaño León, Ana María; Eiriz, Carla; Egéa, Javier; Lagares, Alfonso; i+12 Neurotraumatology Group Collaborators; Paredes, Igor; Fernández Alén, José Antonio; Moreno Gómez, Luis Miguel; García Pérez, Daniel; Chico Fernández, Mario; Barea Mendoza, Jesús Abelardo; Farmacología; Facultades de la UMU::Facultad de MedicinaObjective The volume and location of intracranial hematomas are well-known prognostic factors for traumatic brain injury. The aim of this study was to determine the relationship of serum biomarkers S100β, glial fibrillary acidic protein, neuron-specific enolase, total tau, phosphorylated neurofilament heavy chain, serum amyloid A1 (SAA1), C-reactive protein, procalcitonin (PCT), and chitinase-3-like protein 1 (YKL-40) with traumatic brain injury severity and the amount and location of hemorrhagic traumatic lesions. Methods A prospective observational cohort of 115 patients with a Glasgow Coma Scale (GCS) score of 3–15 were evaluated. Intracranial lesion volume was measured from the semiautomatic segmentation of hematoma on computed tomography using Analyze software. The establishment of possible biomarker cutoff points for intracranial lesion detection was estimated using the Youden Index (J) obtained from the area under the receiver operating characteristic curve. Results SAA1, YKL-40, PCT, and S100β showed the most robust association with level of consciousness, both with total GCS and motor score. Biomarkers significantly correlated with volumetric measurements of subdural hematoma, traumatic subarachnoid hemorrhage, intraparenchymal hemorrhage, intraventricular hemorrhage, and total amount of bleeding. The type of intracranial hemorrhage was associated with various release patterns of neurobiochemical markers. Conclusions YKL-40, SAA1, C-reactive protein, and PCT combined with S100β were the most promising biomarkers to determine the presence, location, and extent of traumatic intracranial lesions. Combination of biomarkers further increased the discriminatory capacity for the detection of intracranial bleeding.
- PublicationRestrictedDensitometric analysis of brain computed tomography as a new prognostic factor in patients with acute subdural hematoma(Journal of Neurosurgery Publishing Group (JNSPG), 2021-07-31) García Pérez, Daniel; Panero Pérez, Irene; Eiriz Fernández, Carla; Moreno Gómez, Luis Miguel; Esteban Sinovas, Olga; Navarro Main, Blanca; Gómez López, Pedro A.; Castaño León, Ana M.; Lagares, Alfonso; FarmacologíaOBJECTIVE Acute subdural hematoma (ASDH) is a major cause of mortality and morbidity after traumatic brain injury (TBI). Surgical evacuation is the mainstay of treatment in patients with altered neurological status or significant mass effect. Nevertheless, concerns regarding surgical indication still persist. Given that clinicians often make therapeutic decisions on the basis of their prognosis assessment, to accurately evaluate the prognosis is of great significance. Unfortunately, there is a lack of specific and reliable prognostic models. In addition, the interdependence of certain well-known predictive variables usually employed to guide surgical decision-making in ASDH has been proven. Because gray matter and white matter are highly susceptible to secondary insults during the early phase after TBI, the authors aimed to assess the extent of these secondary insults with a brain parenchyma densitometric quantitative CT analysis and to evaluate its prognostic capacity. METHODS The authors performed a retrospective analysis among their prospectively collected cohort of patients with moderate to severe TBI. Patients with surgically evacuated, isolated, unilateral ASDH admitted between 2010 and 2017 were selected. Thirty-nine patients were included. For each patient, brain parenchyma density in Hounsfield units (HUs) was measured in 10 selected slices from the supratentorial region. In each slice, different regions of interest (ROIs), including and excluding the cortical parenchyma, were defined. The injured hemisphere, the contralateral hemisphere, and the absolute differences between them were analyzed. The outcome was evaluated using the Glasgow Outcome Scale–Extended at 1 year after TBI. RESULTS Fifteen patients (38.5%) had a favorable outcome. Collected demographic, clinical, and radiographic data did not show significant differences between favorable and unfavorable outcomes. In contrast, the densitometric analysis demonstrated that greater absolute differences between both hemispheres were associated with poor outcome. These differences were detected along the supratentorial region, but were greater at the high convexity level. Moreover, these HU differences were far more marked at the cortical parenchyma. It was also detected that these differences were more prone to ischemic and/or edematous insults than to hyperemic changes. Age was significantly correlated with the side-to-side HU differences in patients with unfavorable outcome. CONCLUSIONS The densitometric analysis is a promising prognostic tool in patients diagnosed with ASDH. The supplementary prognostic information provided by the densitometric analysis should be evaluated in future studies.
- PublicationOpen AccessDiferencias en el funcionamiento ejecutivo en boxeadores universitarios amateurs con distintos niveles de experiencia y categoría de peso(Universidad de Murcia. Servicio de publicaciones, 2023) Guzmán, Jorge; Villalva, Fernando; Bernal, Jorge; Guerrero, VicenteEl boxeo es un deporte popular que implica golpes repetitivos a la cabeza, los cuales podrían producir alteraciones en el funcionamiento cerebral. Aunque existe evidencia del daño cerebral causado por la práctica del boxeo a nivel profesional, permanece la controversia sobre los posibles riesgos en el boxeo aficionado. El objetivo del presente estudio fue analizar si existen diferencias en el funcionamiento ejecutivo en boxeadores universitarios amateursen función de su nivel de experiencia en la práctica deportiva y su interacción con la categoría/peso. Método: Participaron 24 boxeadores mexicanos amateurs agrupados en novatos y experimentados y por su categoría de peso en ligero y medio. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas y Lóbulos Frontales BANFE-2 (Flores-Lázaro et al., 2014). Resultados: se realizó un MANOVA, los contrastes multivariados indican que hay diferencias en la interacción de las variables dependientes, de acuerdo con el nivel de experiencia F(4,17) = 3.75, p= .023, ηp2= .469, 1-β=.56. En particular, las tareas en que se observan diferencias significativas son aquellas que evalúan el control inhibitorio (stroop) y la toma de decisiones de riesgo beneficio (juego de cartas), procesos que se encuentran asociados al funcionamiento de la corteza prefrontal orbito medial. Los hallazgos sugieren que la evaluación del funcionamiento ejecutivo puede ser una herramienta útil para evidenciar cambios funcionales en boxeadores amateur
- PublicationOpen AccessFerroptosis-relevant mechanisms and biomarkers for therapeutic interventions in traumatic brain injury(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Rui, Tongyu; Li, Qianqian; Song, Shunchen; Gao, Yaxuan; Luo, ChengliangTraumatic brain injury (TBI) is one of the most significant health care problems worldwide, causing disability and death especially among young individuals. Although a large range of agents and therapies have been proved beneficial to lesions post- TBI to some extent, effective treatments have not been translated to the clinic. As a newly discovered form of iron-dependent regulated cell death, ferroptosis has been implicated in TBI. In this review, we update the current state of knowledge related to second injuries post-TBI, including ferroptosis, oxidative stress, mitochondrial dysfunction, neuroinflammation and so on, which often lead to chronic symptoms and long-term disability. This review systematically summarizes the latest progress in the pathophysiological mechanisms of TBI, with a focus on providing references for proposing new multi- molecular targets for comprehensive therapeutic strategies based on ferroptosis-relevant mechanisms. In addition, biomarkers are essential diagnostic and prognostic tools in TBI. Several biomarkers associated with the outcome of TBI have been listed in this article, such as Pde10a, MDA, UCH-L1, S100A9, S100B, ALDOC, ACSL4, MBP and F2-Isoprostane. Therefore, the understating of ferroptosis-relevant mechanisms and biomarkers may contribute to development of promising therapies for TBI clinical trials.
- PublicationRestrictedIntracranial pressure monitoring in patients with severe traumatic brain injury: extension of the recommendations and the effect on outcome by propensity score matching(Lippincott, Williams & Wilkins, 2022-09) Castaño-León, Ana M.; Gomez, Pedro A.; Jiménez-Roldán, Luís; Paredes, Igor; Munarriz, Pablo M.; Pérez, Irene Panero; Eiriz Fernández, Carla; Posadas Guillermo García; García Pérez, Daniel; Moreno Gómez, Luis Miguel; Sinovas, Olga Esteban; Posadas García, Guillermo; Lagares, Alfonso; Farmacología; FarmaciaBACKGROUND: Intracranial pressure (ICP) monitoring is recommended for patients with traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) <9 on admission and revealing space-occupying lesions or swelling on computed tomography. However, previous studies that have evaluated its effect on outcome have shown conflicting results. OBJECTIVE: To study the effect of ICP monitoring on outcome after adjustment of patient’s characteristics imbalance and determine the potential benefit on patients with higher GCS that deteriorates early or in the absence of computed tomography results suggesting high ICP. METHODS: We searched for adult patients with TBI admitted between 1996 and 2020 with a GCS <9 on admission or deterioration from higher scores within 24 hours after TBI. Patients were divided into groups if they fulfilled strict (Brain Trauma Foundation guidelines) or extended criteria (patients who worsened after admission or without space-occupying lesions) for ICP monitoring. Propensity score analyses based on nearest neighbor matching was performed. RESULTS: After matching, we analyzed data from 454 patients and 184 patients who fulfilled strict criteria or extended criteria for ICP monitoring, respectively. A decreased on in-hospital mortality was detected in monitored patients following strict and extended criteria. Those patients with a higher baseline risk of poor outcome showed higher odds of favorable outcome if they were monitored. CONCLUSION: ICP monitoring in patients with severe TBI within 24 hours after injury following strict and extended criteria was associated with a decreased in-hospital mortality. The identification of patients with a higher risk of an unfavorable outcome might be useful to better select cases that would benefit more from ICP monitoring.
- PublicationOpen AccessMedian nerve electrical stimulation improves traumatic brain injury by reducing TACR1 to inhibit nuclear factor-κB and CCL7 activation in microglia(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Sun, Fan; Li, Xiaodong; Wang, Xiao-Wei; Ou, Yali; Li, Xuesong; Shi, MinThe existing report elucidates that median nerve electrical stimulation (MNS) plays a role in treating traumatic brain injury (TBI). Herein, we explored the mechanism of MNS in TBI. A TBI-induced coma model (skull was hit by a cylindrical impact hammer) was established in adult Sprague-Dawley rats. Microglia were isolated from newborn Sprague-Dawley rats and was injured by lipopolysaccharide (LPS; 10 ng/mL). Consciousness was assessed by sensory and motor functions. Brain tissue morphology was detected using hematoxylin-eosin staining assay. Ionized calcium binding adapter molecule 1, NeuN and tachykinin receptor 1 (TACR1) level were detected by immunohistochemical assay. Levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme linked immune sorbent assay (ELISA). Levels of TACR1, C-C motif chemokine ligand 7 (CCL7), phosphorylation (p)-P65 and P65 were assessed by quantitative real time polymerase chain reaction (qRT-PCR) and western blot. M1 markers (inducible nitric oxide synthase and CD86) and M2 markers (arginase-1 (Arg1) and chitinase 3-like 3 (YM1)) of microglia as well as the transfection efficiency of short hairpin TACR1 (shTACR1) were assessed by qRT-PCR. Immunofluorescence and flow cytometry assay were used to detect microglia morphology and neuron apoptosis. MNS reduced neuron injury and microglia activation in the TBI-induced rat coma model. MNS reversed the effects of TBI on levels of inflammation-related factors, M1/M2 microglia markers, TACR1, p-P65/P65 and CCL7 in rats. shTACR1 reversed the effects of LPS on inflammation-related factors, M1/M2 microglia markers, microglia activation, neuron apoptosis, p-P65/P65 value and CCL7 level. Our results revealed that MNS improved TBI by reducing TACR1 to inhibit nuclear factor-κB (NF-κB) and CCL7 activation in microglia.
- PublicationOpen AccessMiR-124-3p attenuates brain microvascular endothelial cell injury in vitro by promoting autophagy(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zhao, Jing; Wang, Yan; Wang, Dong; Yan, Wei; Zhang, Shishuang; Li, Dai; Han, Zhaoli; Chen, Fanglian; Le, Ping. Traumatic brain injury (TBI) can cause the pathological disruption of the blood-brain barrier (BBB) and associated neurological injury. Reducing the severity of such barrier disruption following TBI can decrease the degree of brain edema, suppress intracranial inflammation, and thereby protect against neurological damage. The BBB is made up of brain microvascular endothelial cells (BMVECs), neurons, pericytes, astrocytes, and extracellular matrix components. In prior analyses, we have demonstrated that miR-124-3p expression is enhanced in microglia-derived exosomes following TBI, with this miRNA being capable of promoting neural repair after such injury. Based upon these results, the present study was formulated to examine the impact of miR-124-3p on BMVEC function and to evaluatethe mechanistic basis for its activity by overexpressing miR-124-3p in these endothelial cells. We utilized a bEnd.3 cell scratch wound in vitro model to simulate TBI-associated brain microvascular endothelial cell injury. Lipofectamine3000 was used to transfect endothelial cells such that they overexpressed miR-124-3p. Fluorescence microscopy was used to observe the effects of miR-124-3p expression on these endothelial cells. TUNEL+CD31 immunofluorescence stainingwas employed to observe endothelial cell apoptosis. Tight junctions were observed via ionconductivity microscopy. Western blotting was used to detect the expression of tight junction proteins (occludin, ZO-1), autophagy-associated proteins (Beclin1, p62, LC3-II/LC3-I), and mTOR-associated proteins (p-mTOR, PDE4B). Chloroquine was used to treat these injured endothelial cells overexpressing miR-124-3p, and endothelial cell apoptosis was assessed via TUNEL+CD31 immunofluorescence staining. We found that the upregulation of miR-124-3p was sufficient to suppress bEnd.3 cell apoptotic death following in vitro scratch injury while promoting the upregulation of the tight junction proteins ZO-1 and occludin in these cells, thereby reducing the degree of leakage across the cerebral microvascular endothelial barrier. These protective effects may be related to the ability of miR124-3p to suppress mTOR signaling and to induce autophagic activity within BMVECs. These data support a model wherein miR-124-3p can inhibit mTOR signaling and promote autophagic induction in BMVECs, thereby protecting these cells against TBIinduced damage.
- PublicationRestrictedNovel CT‑based parameters assessing relative cross‑sectional area to guide surgical management and predict clinical outcomes in patients with acute subdural hematoma(Springer, 2023) García Pérez, Daniel; Castaño León, Ana María; Moreno Gómez, Luis Miguel; Esteban Sinovas, Olga; García Posadas, Guillermo; Paredes, Igor; Gómez López, Pedro A.; Lagares, Alfonso; Panero Pérez, Irene; FarmacologíaIntroduction Acute subdural hematoma (aSDH) is one of the most devastating entities secondary to traumatic brain injury (TBI). Even though radiological computed tomography (CT) findings, such as hematoma thickness (HT), midline shift (MLS), and MLS/HT ratio, have an important prognostic role, they suffer from important drawbacks. We hypothesized that relative cross-sectional area (rCSA) of specific brain regions would provide valuable information about brain compression and swelling, thus being a key determining factor governing the clinical course. Methods We performed an 8-year retrospective analysis of patients with moderate to severe TBI with surgically evacuated, isolated, unilateral aSDH. We investigated the influence of aSDH rCSA and ipsilateral hemisphere rCSA along the supratentorial region on the subsequent operative technique employed for aSDH evacuation and patient’s clinical outcomes (early death and Glasgow Outcome Scale [GOS] at discharge and after 1-year follow-up). Different conventional radiological variables were also assessed. Results The study included 39 patients. Lower HT, MLS, hematoma volume, and aSDH rCSA showed a significant association with decompressive craniectomy (DC) procedure. Conversely, higher ipsilateral hemisphere rCSA along the dorso-ventral axis and, specifically, ipsilateral hemisphere rCSA at the high convexity level were predictors for DC. CT segmentation analysis exhibited a modest relationship with early death, which was limited to the basal supratentorial subregion, but could not predict long-term outcome. Conclusion rCSA is an objectifiable and reliable radiologic parameter available on admission CT that might provide valuable information to optimize surgical treatment.
- PublicationOpen AccessPrincipales causas asociadas al traumatismo craneoencefálico en ancianos(Murcia : Servicio de Publicaciones de la Universidad de Murcia, 2011) Pinheiro, A.L.; De Almeida, F.M.; Barbosa, I.V.; Mesquita Melo, E.; Borges Studart, R.M.; De Figueiredo Carvalho, Z.M.Estudios demuestran un aumento en el número de traumas en ancianos, lo que puede estar asociado al crecimiento de esta población. El objetivo del estudio fue evaluar las características de los ancianos afectados por trauma craneoencefálico (TCE) e identificar las causas asociadas a dicho traumatismo en ancianos. Estudio exploratorio descriptivo, realizado con 41 ancianos, víctimas de TCE, atendidos en hospital público, referencia en trauma, localizado en Fortaleza-Ceará. Los datos fueron colectados en los meses de febrero y marzo de 2009, por medio de un guión de entrevista estructurado, conteniendo datos de identificación y cuestiones relacionadas a las características del accidente que ocasionó el TCE. Los aspectos éticos y legales fueron contemplados. La mayoría de los participantes es de sexo masculino (85,3%), en situación económicamente activa; 75,7% residen con familiares. La principal causa del TCE son las caídas (34,2%). Respecto al lugar donde ocurrió el accidente que generó el TCE, 23 (56,1%) fue en la calle. Los traumatismos craneoencefálicos en los ancianos constituyen un gran problema de salud pública, siendo fundamental la prevención de accidentes en dicha población.
- PublicationOpen AccessLa relación entre la percepción del cuidador sobre los síntomas derivados del daño cerebral en personas con traumatismos craneoencefálicos y su propia Salud Mental(Murcia: Servicio de Publicaciones de la Universidad de Murcia, 2015) De los Reyes-Aragón, Carlos José; Olabarrieta Landa, Laiene; Caracuel Romero, Alfonso; Arango Lasprilla, Juan CarlosObjetivo: Determinar si existe una relación entre la percepción que tiene el cuidador de los síntomas que presentan los pacientes con traumatismos craneoencefálicos (TCE) y su salud mental. Participantes: Se entrevistó a 50 cuidadores de individuos con TCE de la ciudad de Barranquilla, Colombia, a quienes se les aplicó la escala de satisfacción con la vida, la versión en español del Patient Health Questionary-9, la escala de sobrecarga de Zarit, la escala de autoestima de Rosenberg, el inventario de ansiedad estado-rasgo y un cuestionario de 22 preguntas que evaluó la percepción de síntomas del individuo con TCE, compuesto por cuatro grupos de síntomas: cognitivos, neuroconductuales, físicos y sociales. Resultados: Los análisis de correlación canónica revelaron que a mayor número de síntomas que se perciben en el paciente, peor es la salud mental que tienen los cuidadores, específicamente se encontró que a mayor percepción de síntomas neuroconductuales en el paciente mayor sobrecarga, mayor depresión y menor autoestima en el cuidador. Conclusiones: Los resultados sugieren la necesidad de desarrollar e implementar programas de intervención psicoterapéutica, así como terapia de rehabilitación cognitiva, con el fin de reducir o eliminar los problemas neuroconductuales en personas con TCE en Colombia. De igual forma, es importante el diseño de intervenciones que trabajen de manera paralela con los cuidadores y familiares para orientarlos respecto al impacto que puede tener el TCE tanto en la vida del paciente, como en la familia, brindándoles, además, herramientas para manejar la aparición de problemas emocionales, como la depresión, la baja autoestima y la sobrecarga.
- PublicationOpen AccessSerum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility(American Association of Neurological Surgeons, 2022-07-15) Castaño-Leon, Ana M.; Sánchez Carabias, Cristina; Hilario, Amaya; Ramos, Ana; Navarro-Main, Blanca; Paredes, Igor; Munarriz, Pablo M.; Panero, Irene; Eiriz Fernández, Carla; García Pérez, Daniel; Moreno-Gómez, Luis Miguel; Estéban-Sinova, Olga; Garcia Posadas, Guillermo; Gomez, Pedro A.; Lagares, Alfonso; Farmacología; FarmaciaOBJECTIVE: Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomarkers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored. METHODS: Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale–Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis. RESULTS: A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome. CONCLUSIONS: UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome.
- PublicationOpen AccessSeven days post-injury fate and effects of genetically labelled adipose-derived mesenchymal cells on a rat traumatic brain injury experimental model(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Dori, Ioanna; Petrakis, Spyros; Giannakopoulou, Aggeliki; Bekiari, Chryssa; Grivas, Ioannis; Siska, Evangelia K.; Koliakos, Georgios; Papadopoulos, Georgios C.Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissuederived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus. Venus+ASCs were transplanted intra-cerebroventricularly (ICV), on a rat TBI model and their survival, fate and effects on host brain responses were examined at seven days post-injury (7dPI). We provide evidence that Venus+ASCs survived, migrated into the periventricular striatum and were negative for neuronal or glial lineage differentiation markers. Venus+ASCs stimulated the proliferation of endogenous neural stem cells (NSCs) in the brain neurogenic niches, the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). It was also evident that Venus+ASCs modify the host brain’s cellular microenvironment both at the injury site and at their localization area by promoting a significant reduction of the lesion area, as well as altering the post-injury, pro-inflammatory profile of microglial and astrocytic cell populations. Our data support the view that ICV transplantation of ASCs induces alterations in the host brain’s cellular response to injury that may be correlated to a reversal from a detrimental to a beneficial state which is permissive for regeneration and repair.
- PublicationOpen AccessThe application of mesenchymal stem cells in the treatment of traumatic brain injury: Mechanisms, results, and problems(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhang, Ying; Zheng, Zejun; Sun, Jinmeng; Xu, Shuangshuang; Wei, Yanan; Ding, Xiaoling; Ding, GangMesenchymal stem cells (MSCs) are multipotent stromal cells that can be derived from a wide variety of human tissues and organs. They can differentiate into a variety of cell types, including osteoblasts, adipocytes, and chondrocytes, and thus show great potential in regenerative medicine. Traumatic brain injury (TBI) is an organic injury to brain tissue with a high rate of disability and death caused by an external impact or concussive force acting directly or indirectly on the head. The current treatment of TBI mainly includes symptomatic, pharmacological, and rehabilitation treatment. Although some efficacy has been achieved, the definitive recovery effect on neural tissue is still limited. Recent studies have shown that MSC therapies are more effective than traditional treatment strategies due to their strong multi-directional differentiation potential, self-renewal capacity, and low immunogenicity and homing properties, thus MSCs are considered to play an important role and are an ideal cell for the treatment of injurious diseases, including TBI. In this paper, we systematically reviewed the role and mechanisms of MSCs and MSC-derived exosomes in the treatment of TBI, thereby providing new insights into the clinical applications of MSCs and MSC-derived exosomes in the treatment of central nervous system disorders
- PublicationOpen AccessTraumatic brain injury: Estimate of the age of the injury based on neuroinflammation, endothelial activation markers and adhesion molecules(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) dell'Aquila, Massimiliano; Maiese, Aniello; De Matteis, Alessandra; Viola, Rocco Valerio; Arcangeli, Mauro; La Russa, Raffaele; Fineschi, VittorioStudies on traumatic brain injury (TBI) are applicable not only in the clinical context, but also in the forensic field. Over time, the literature has accumulated scientific evidence supporting the use of specific histopathological tests in dating traumatic brain injuries. In primary damage, cell death occurs by necrosis/apoptosis. In secondary injury, the underlying mechanisms are inflammation and ischemia. The inflammatory response of the central nervous system (CNS) follows the common steps of the innate response. In head injury, the blood brain barrier (BBB) undergoes both functional damage and, subsequently, finer structural changes. Scientific evidence has shown modifications of the junctional-endothelial system that favors the extravasation of immunocompetent cells. The histological evaluation of the subdural hematoma, of the cerebral contusions, of the diffuse axonal damage can certainly bring useful elements, with limitations, to the chronological evaluation of the lesions. Many markers have been used to better define the dating of the head injury. Several authors also analyzed the usefulness of secondary damage markers in brain tissue. The progress achieved with immunohistochemistry is significant compared to the use of routine staining. With immunohistochemistry it is possible to identify much narrower and more precise time intervals and, above all, with greater probative reliability. Recently attention has been paid to the modification of structural proteins and miRNAs. Future research is already started and entrusted to multidisciplinary teams that know how to combine their specific skills in search of a reproducible standard of known and sufficient accuracy