Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function after Chronic Traumatic Brain Injury.

Human neural stem cells (hNSCs) have potential as a cell therapy after traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from ongoing culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks-a more clinically relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested after long-term cryostorage and thawing before transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At four weeks post-injury, 6 × 105 freshly thawed hNSCs were transplanted into six injection sites (two ipsi- and four contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk taking in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume, and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to improve function after TBI and demonstrate that long-term biobanking of cells and thawing aliquots before use may be suitable for clinical deployment.

Investigating music-based cognitive rehabilitation for individuals with moderate to severe chronic acquired brain injury: A feasibility experiment.

BACKGROUND: Acquired brain injuries often cause cognitive impairment, significantly impacting participation in rehabilitation and activities of daily living. Music can influence brain function, and thus may serve as a uniquely powerful cognitive rehabilitation intervention. OBJECTIVE: This feasibility study investigated the potential effectiveness of music-based cognitive rehabilitation for adults with chronic acquired brain injury. METHODS: The control group participated in three Attention Process Training (APT) sessions, while the experimental group participated in three Music Attention Control Training (MACT) sessions. Pre-and post- testing used the Trail Making A & B, Digit Symbol, and Brown-Peterson Task as neuropsychological tests. RESULTS: ANOVA analyses showed no significant difference between groups for Trail A Test, Digit Symbol, and Brown-Peterson Task. Trail B showed significant differences at post-test favouring MACT over APT. The mean difference time between pre-and post-tests for the Trail B Test was also significantly different between APT and MACT in favour of MACT using a two-sample t-test as well as a follow-up nonparametric Mann Whitney U-test. CONCLUSIONS: The group differences found in the Trail B tests provided preliminary evidence for the efficacy of MACT to arouse and engage attention in adults with acquired brain injury.

Yoga improves balance, mobility, and perceived occupational performance in adults with chronic brain injury: A preliminary investigation.

BACKGROUND AND PURPOSE: This was a preliminary investigation to investigate potential benefits of group yoga, as past work has indicated that one-on-one yoga can improve functional deficits in adults with brain injury. MATERIALS AND METHODS: Participants served as their own controls. Nine participants with chronic brain injury were recruited, and seven (four female) completed the study. Performance measures of balance and mobility and self-reported measures of balance confidence, pain, and occupational performance and satisfaction were used. Data were collected 3 times: baseline (study onset), pre-yoga (after an 8-week no-contact period), and post-yoga (after 8 weeks of yoga). Group yoga was led by a yoga instructor/occupational therapist, and sessions lasted 1 h and occurred twice a week. RESULTS: No participants withdrew due to adverse effects from yoga. There were no significant changes between baseline and pre-yoga. Significant improvement was observed post-yoga in balance (p = 0.05), mobility (p = 0.03), and self-reported occupational performance (p = 0.04). CONCLUSION: We observed significant improvements in balance, mobility, and self-reported occupational performance in adults with chronic brain injury.

High-Definition Transcranial Direct Current Stimulation to Improve Verbal Retrieval Deficits in Chronic Traumatic Brain Injury.

Chronic verbal retrieval deficits have been noted in traumatic brain injury (TBI), but no U.S. Food and Drug Administration-approved interventions are available. The present study investigated whether 10 sessions of 20 min of 1 mA anodal high-definition transcranial direct current stimulation (HD-tDCS) targeting pre-supplementary motor area/dorsal anterior cingulate cortex (preSMA/dACC) compared with sham HD-tDCS would improve verbal retrieval deficits in TBI patients. Improvements in verbal retrieval processes were observed up to 8 weeks post-treatment. Thus, potential dysfunction to verbal retrieval circuitry in TBI appears amenable to remediation through electromodulation with HD tDCS to the preSMA/dACC. Although further studies clarifying mechanisms by which tDCS brought about these improvements will likely inform refinements in the application of this therapeutic technique, the findings suggest the efficacy of using HD-tDCS to target other systems vulnerable to TBI to improve functioning.

Exploration of gray matter correlates of cognitive training benefit in adolescents with chronic traumatic brain injury.

Sustaining a traumatic brain injury (TBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood. This study investigated gray matter plasticity following 2 months of cognitive training in young patients with TBI. Sixteen adolescents in the chronic stage of moderate-severe-TBI (9 male, mean age = 15y8m ±â€¯1y7m) were enrolled in a cognitive computerized training program for 8 weeks (5 times/week, 40 min/session). Pre-and post-intervention, and 6 months after completion of the training, participants underwent a comprehensive neurocognitive test-battery and anatomical Magnetic Resonance Imaging scans. We selected 9 cortical-subcortical Regions-Of-Interest associated with Executive Functioning (EF-ROIs) and 3 control regions from the Desikan-Killiany atlas. Baseline analyses showed significant decreased gray matter density in the superior frontal gyri p = 0.033, superior parietal gyri p = 0.015 and thalamus p = 0.006 in adolescents with TBI compared to age and gender matched controls. Linear mixed model analyses of longitudinal volumetric data of the EF-ROI revealed no strong evidence of training-related changes in the group with TBI. However, compared to the change over time in the control regions between post-intervention and 6 months follow-up, the change in the EF-ROIs showed a significant difference. Exploratory analyses revealed a negative correlation between the change on the Digit Symbol Substitution test and the change in volume of the putamen (r = -0.596, p = 0.015). This preliminary study contributes to the insights of training-related plasticity mechanisms after pediatric-TBI.

Treatments and rehabilitation in the acute and chronic state of traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of acquired disability globally, and effective treatment methods are scarce. Lately, there has been increasing recognition of the devastating impact of TBI resulting from sports and other recreational activities, ranging from primarily sport-related concussions (SRC) but also more severe brain injuries requiring hospitalization. There are currently no established treatments for the underlying pathophysiology in TBI and while neuro-rehabilitation efforts are promising, there are currently is a lack of consensus regarding rehabilitation following TBI of any severity. In this narrative review, we highlight short- and long-term consequences of SRCs, and how the sideline management of these patients should be performed. We also cover the basic concepts of neuro-critical care management for more severely brain-injured patients with a focus on brain oedema and the necessity of improving intracranial conditions in terms of substrate delivery in order to facilitate recovery and improve outcome. Further, following the acute phase, promising new approaches to rehabilitation are covered for both patients with severe TBI and athletes suffering from SRC. These highlight the need for co-ordinated interdisciplinary rehabilitation, with a special focus on cognition, in order to promote recovery after TBI.

Sensory Sensitivity in TBI: Implications for Chronic Disability.

PURPOSE OF REVIEW: This review investigates the relationship between sensory sensitivity and traumatic brain injury (TBI), and the role sensory sensitivity plays in chronic disability. RECENT FINDINGS: TBI is a significant cause of disability with a range of physical, cognitive, and mental health consequences. Sensory sensitivities (e.g., noise and light) are among the most frequently reported, yet least outwardly recognizable symptoms following TBI. Clinicians and scientists alike have yet to identify consistent nomenclature for defining noise and light sensitivity, making it difficult to accurately and reliably assess their influence. Noise and light sensitivity can profoundly affect critical aspects of independent function including communication, productivity, socialization, cognition, sleep, and mental health. Research examining the prevalence of sensory sensitivity and evidence for the association of sensory sensitivity with TBI is inconclusive. Evidence-based interventions for sensory sensitivity, particularly following TBI, are lacking.

Hypoaminoacidemia Characterizes Chronic Traumatic Brain Injury.

Individuals with a history of traumatic brain injury (TBI) are at increased risk for a number of disorders, including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. However, mediators of the long-term morbidity are uncertain. We conducted a multi-site, prospective trial in chronic TBI patients (∼18 years post-TBI) living in long-term 24-h care environments and local controls without a history of head injury. Inability to give informed consent was exclusionary for participation. A total of 41 individuals (17 moderate-severe TBI, 24 controls) were studied before and after consumption of a standardized breakfast to determine if concentrations of amino acids, cytokines, C-reactive protein, and insulin are potential mediators of long-term TBI morbidity. Analyte concentrations were measured in serum drawn before (fasting) and 1 h after meal consumption. Mean ages were 44 ± 15 and 49 ± 11 years for controls and chronic TBI patients, respectively. Chronic TBI patients had significantly lower circulating concentrations of numerous individual amino acids, as well as essential amino acids (p = 0.03) and large neutral amino acids (p = 0.003) considered as groups, and displayed fundamentally altered cytokine-amino acid relationships. Many years after injury, TBI patients exhibit abnormal metabolic responses and altered relationships between circulating amino acids, cytokines, and hormones. This pattern is consistent with TBI, inducing a chronic disease state in patients. Understanding the mechanisms causing the chronic disease state could lead to new treatments for its prevention.

Improved Function After Deep Brain Stimulation for Chronic, Severe Traumatic Brain Injury.

BACKGROUND: Severe traumatic brain injury (TBI) damages the frontal lobes and connecting networks, which impairs executive functions, including the ability to self-regulate. Despite significant disabling effects, there are few treatment options in the chronic phase after injury. OBJECTIVE: To investigate the safety and potential effectiveness of deep brain stimulation (DBS) for individuals with chronic, disabling TBI and problems of behavioral and emotional self-regulation. METHODS: This study was an open-label, prospective design with serial assessments of behavioral outcomes and positron emission tomography 2 years after DBS implantation. Four participants 6 to 21 years after severe TBIs from automobile crashes were included. Although alert and volitional, all experienced significant executive impairments, including either impulsivity or reduced initiation. DBS implants were placed bilaterally in the nucleus accumbens and anterior limb of the internal capsule to modulate the prefrontal cortex. RESULTS: The procedure was safe, and all participants had improved functional outcomes. Two years after implantation, 3 met a priori criteria for improvement on the Mayo-Portland Adaptability Inventory-4. Improvement was due largely to better emotional adjustment, although 1 participant showed marked increases in multiple domains. Significant improvement in a composite score of functional capacity indicated improved independence in self-care and activities of daily living. The pattern of change in cognition corresponded with changes in activation of the prefrontal cortex observed in serial scanning. CONCLUSION: This first study of DBS to this target for severe TBI supports its safety and suggests potential effectiveness to improve function years after injury. The primary impact was on behavioral and emotional adjustment, which in turn improved functional independence. ABBREVIATIONS: DBS, deep brain stimulationIC, internal capsuleMPAI-4, Mayo-Portland Adaptability Inventory-4NAcc, nucleus accumbensTBI, traumatic brain injury.

Clinical results in brain injury trials using HBO2 therapy: Another perspective.

The current debate surrounding the use of hyperbaric oxygen (HBO2) for neurological indications, specifically mild to moderate chronic traumatic brain injury (mTBI) and post-concussion syndrome (PCS), is mired in confusion due to the use of non-validated controls and an unfamiliarity by many practitioners of HBO2 therapy with the experimental literature. In the past 40 years, the use of an air sham (21% oxygen, 1.14-1.5 atmospheres absolute/atm abs) in clinical and animal studies, instead of observational or crossover controls, has led to false acceptance of the null hypothesis (declaring no effect when one is present), due to the biological activity of these "sham" controls. The recent Department of Defense/Veterans Administration (DoD/VA) sponsored trials, previous published reports on the use of HBO2 therapy on stroke and mTBI and preliminary reports from the HOPPS Army trial, have helped to highlight the biological activity of pressurized air, validate the development of a convincing control for future studies and demonstrate the effectiveness of a hyperbaric intervention for mTBI/ PCS. Approval of HBO2 for neurological indications, especially for mTBI/PCS, should be granted at the federal, state and certifying body levels as a safe and viable treatment for recovery in the post-acute phase.

Ice Hockey Summit II: zero tolerance for head hits and fighting.

OBJECTIVE: To present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards; and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. RESULTS: The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. CONCLUSIONS: The highest priority action items identified from the Summit includes the following: (1) eliminate head hits from all levels of ice hockey, (2) change body-checking policies, and (3) eliminate fighting in all amateur and professional hockey.

Brain injury after cardiac surgery.

In patients undergoing cardiac surgery, postoperative brain injury significantly contributes to increase morbidity and mortality and has negative consequences on quality of life and costs. Moreover, over the past years, compelling medical and technological improvements have allowed an even older patients' population, with several comorbidities, to be treated with cardiac surgery; however, the risk of brain injury after such interventions is also increased in these patients. With the aim of improving post-operative neurological outcome, a variety of neuromonitoring methods and devices have been introduced in clinical practice. These techniques allow the assessment of a number of parameters, such as cerebral blood flow, brain embolic events, cerebral cortical activity, depth of anesthesia and brain oxygenation. Some of them have been used to optimize the hemodynamic management of such patients and to select specific therapeutic interventions. Also, various pharmacological and non-pharmacological approaches have been proposed to minimize the incidence of brain injury in this setting. In this review we describe the risk factors and mechanisms of cerebral injury after cardiac surgery and focus on monitoring techniques and clinical strategies that could help clinicians to minimize the incidence of brain injury.

Speech-language pathology and concussion management in intercollegiate athletics: the Miami University Concussion Management Program.

PURPOSE: The Miami University Concussion Management Program was established in 1999 to assess, manage, and monitor athletes who sustain concussions and experience neurobehavioral and neurocognitive symptoms secondary to their injury. The purpose of this article is to describe the established procedures of one of the oldest university-based interdisciplinary concussion management programs that is coordinated by speech-language pathologists (SLP). METHOD: The theoretical and clinical underpinnings of baseline and postconcussion neurocognitive assessment and management procedures are discussed. Additionally, 2 illustrative case studies are presented to demonstrate the evolution and implementation of the interdisciplinary concussion management protocol and to present different patterns of concussion symptoms and recovery. Paper and computer-based neurocognitive assessment protocols are discussed and integrated in the case studies. RESULTS/CONCLUSIONS: Successful management of sport-related concussion requires an interdisciplinary team that understands the unique neurobehavioral and neurocognitive symptoms associated with sports concussions. SLPs can play a valuable role on the interdisciplinary team in the prompt and appropriate management of postconcussion symptoms so that athletes can successfully return to their athletic, academic, and social activities.

Chronic traumatic encephalopathy: where are we and where are we going?

Chronic traumatic encephalopathy (CTE, previously called punch drunk and dementia pugilistica) has a rich history in the medical literature in association with boxing, but has only recently been recognized with other contact sports, such as football and ice hockey, as well as with military blast injuries. CTE is thought to be a neurodegenerative disease associated with repeated concussive and subconcussive blows to the head. There is characteristic gross and microscopic pathology found in the brain, including frontal and temporal atrophy, axonal degeneration, and hyperphosphorylated tau and TAR DNA-binding protein 43 pathology. Clinically, there are characteristic progressive deficits in cognition (memory, executive dysfunction), behavior (explosivity, aggression), mood (depression, suicidality), and motor function (parkinsonism), which correlate with the anatomic distribution of brain pathology. While CTE shares clinical and neuropathological traits with other neurodegenerative diseases, the clinical syndrome and the neuropathology as a whole are distinct from other neurodegenerative diseases. Here we review the CTE literature to date. We also draw on the literature from mild traumatic brain injury and other neurodegenerative dementias, particularly when these studies provide guidance for future CTE research. We conclude by suggesting seven essential areas for future CTE research.

Análisis del efecto de las actividades físicas grupales en pacientes con daño cerebral adquirido en fase subaguda / Analysis of the effect of physical group activities in patients with acquired brain injury in the subacute phase

Introducción. El daño cerebral adquirido (DCA) hace referencia a cualquier tipo de lesión no degenerativa que se produce en el cerebro. Las actividades físicas grupales (AFG) se presentan como un tratamiento efectivo para la mejora de la capacidad funcional. Objetivo. Analizar la eficacia de un programa de AFG en personas con DCA en fase subaguda para su integración física en la comunidad. Pacientes y métodos. Treinta y tres pacientes con DCA, con una edad de 33,18 ± 10,39 años, participaron en un programa de AFG (talleres de circuito, equilibrio simple, equilibrio dual, desplazamiento dual y actividades físico-deportivas) de 10 semanas. Al comenzar y concluir el programa se evaluaron las variables de velocidad (prueba de velocidad de la marcha en 10 metros), resistencia (prueba de marcha de seis minutos), equilibrio dinámico (Step Test), capacidad funcional (Timed Up & Go), escala de percepción de seguridad (Activities-specific Balance Confidence Scale) y Physical Activity and Disability Survey (PADS), el promedio por hora de la intensidad de la actividad y el número de pasos fuera del centro de rehabilitación (usando monitores de actividad física). La prueba t para muestras relacionadas se utilizó para evaluar las diferencias en las variables. Resultados. Se hallaron diferencias significativas (p ≤ 0,05) en las variables de velocidad, resistencia, equilibrio, capacidad funcional, percepción de seguridad, percepción de realización de actividad general (pregunta 3 del PADS) y número de pasos. Conclusión. Los programas de AFG mejoran las capacidades físicas, percepción de seguridad, realización de actividad en general y número de pasos, lo que puede conllevar una mayor participación en la comunidad (AU)

Introduction. The term acquired brain injury (ABI) refers to any kind of non-degenerative injury that occurs in the brain. Group physical activities (GPA) are an effective treatment that improves the functional capacity. Aims. To analyse the efficacy of a GPA programme in persons with ABI in the subacute phase so that they can be reintegrated physically in the community.Patients and methods. Thirty-three patients with ABI, aged 33.18 ± 10.39 years, took part in a 10-week GPA programme (circuit workshops, simple equilibrium, dual equilibrium, dual displacement and physical-sports activities). At the start and the end of the programme the following variables were evaluated: speed (10-metre walking speed test), resistance (sixminute walk test), dynamic balance (Step Test), functional capacity (Timed Up & Go), safety perception scale (Activitiesspecific Balance Confidence Scale) and Physical Activity and Disability Survey (PADS), the average per hour intensity of the ctivity and the number of steps outside the rehabilitation centre (using physical activity monitors). The t test for related samples was used to evaluate the differences among the variables. Results. Significant differences were found (p ≤ 0.05) in the variables speed, resistance, balance, functional capacity, perception of safety, perception of general activity performance (question 3 of the PADS) and number of steps. Conclusions. GPA programmes improve physical capacities, perception of safety, performance of activity in general and the number of steps, which can lead to greater participation in the community (AU)

Chronic traumatic encephalopathy - neuropathology in athletes and war veterans.

OBJECTIVE: The neuropathologic findings of chronic traumatic encephalopathy (CTE) were first described almost 40 years after the first clinical reports. We reviewed the literature and describe the neuropathological findings seen primarily in professional athletes and more recently, in war veterans. METHODS: We reviewed the literature of CTE concentrating on references that focused on the correlation of clinical findings with the neuropathologic changes. The pathobiology and proposed mechanisms of injury are described. Diagnostic modalities and various diagnostic criteria of CTE are reviewed. RESULTS: We are beginning to understand the neuropathologic basis of CTE, which appears to be a consequence of repetitive mild brain injuries. There appear to be reproducible criteria for the post-mortem diagnosis of CTE and the neuropathologic findings are becoming more widely accepted. More research is required to elucidate the risk factors that predispose athletes and war veterans to CTE. There is also a need for more diagnostic markers and a method to assess CTE in patients prior to death. The neuropathologic findings of a progressive tauopathy including the presence of numerous neurofibrillary tangles (NFTs), rare neuritic plaques, and widespread expression of TDP-43 (transactive response [TAR] DNA binding protein 43) also require further study. DISCUSSION: The potential prevalence of CTE, as well as the vulnerable populations involved, makes research into this topic crucial. Currently, a comprehensive neurological exam, neuropsychiatric assessment, and standard radiographic techniques such as conventional MRI are the mainstay of diagnosis. There is a pressing need for the prevention of CTE and the development of non-invasive diagnostic tests in order to develop therapies that may be of clinical use to athletes and blast injury veterans during their lifetimes.

Chronic traumatic encephalopathy.

Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research.

Pediatric providers' self-reported knowledge, practices, and attitudes about concussion.

OBJECTIVE: To determine the self-reported practices and attitudes surrounding concussion diagnosis and management in a single, large pediatric care network. METHODS: A cross-sectional survey was distributed to pediatric primary care and emergency medicine providers in a single, large pediatric care network. For all survey participants, practices and attitudes about concussion diagnosis and treatment were queried. RESULTS: There were 145 responses from 276 eligible providers, resulting in a 53% response rate, of which 91% (95% confidence interval [CI]: 86%-95%) had cared for at least 1 concussion patient in the previous 3 months. A Likert scale from 1 "not a barrier" to 5 "significant barrier" was used to assess providers' barriers to educating families about the diagnosis of concussion. Providers selected 4 or 5 on the scale for the following barriers and frequencies: inadequate training to educate 16% (95% CI: 11%-23%), inadequate time to educate 15% (95% CI: 12%-24%), and not my role to educate 1% (95% CI: 0.4%-5%). Ninety-six percent (95% CI: 91%-98%) of providers without a provider decision support tool (such as a clinical pathway or protocol) specific to concussion, and 100% (95% CI: 94%-100%) of providers without discharge instructions specific to concussion believed these resources would be helpful. CONCLUSIONS: Although pediatric primary care and emergency medicine providers regularly care for concussion patients, they may not have adequate training or infrastructure to systematically diagnose and manage these patients. Specific provider education, decision support tools, and patient information could help enhance and standardize concussion management.

Daño cerebral traumático: fallo de la vía intravenosa para la administración de células madre estromales de médula ósea como tratamiento de las secuelas neurológicas crónicas / Traumatic brain injury: failure of the intravenous route for the administration of bone marrow stromal stem cells as treatment of chronic neurological sequels

Objetivo: Estudiar el posible efecto terapéutico de la administración intravenosa de células madre estromales (CME) obtenidas de médula ósea para tratar las secuelas neurológicas en fase crónica tras una lesión cerebral traumática. Material y método: Se realizó un modelo de lesión cerebral traumática en ratas Wistar adultas y se estudió el déficit neurológico inducido en el curso de los dos meses siguientes, por medio del test mNSS y el test Smart. Tras ese tiempo, en fase de secuelas crónicamente establecidas, se administraron intravenosamente 15 x 106 CME (n:10) o suero fisiológico (n:10). En los dos meses siguientes se estudió la posible modificación de las secuelas neurológicas. Resultados: Cuando se compararon los resultados de la valoración funcional entre ambos grupos experimentales, no se observaron diferencias estadísticamente significativas. Conclusión: Nuestros resultados sugieren que el trasplante de CME por vía intravenosa, en una fase de secuelas crónicamente establecidas tras una lesión traumática cerebral grave, no tiene efecto terapéutico (AU)

Objective: We studied the possible therapeutic effect of intravenous administration (noninvasive method) of BMSCs to treat neurological sequels in a chronic stage after TBI. Material and method: A model of TBI in adult Wistar rats was performed and we studied the neurological deficit induced in the course of two months, through the mNSS and Smart tests. After this time, with established sequels, 15 x 106 BMSCs (n = 10) or saline (n = 10) were administered intravenously. Changes in the neurological deficits were studied in two months. Results: Comparison of functional changes between both experimental groups showed no statistically significant differences. Conclusions: Our results suggest that transplantation of BMSCs intravenously, at a stage of established sequels after severe TBI, has no therapeutic effect (AU)