Hipotermia terapêutica no traumatismo crânio-encefálico

Enquadramento – A hipotermia terapêutica consiste na redução controlada da temperatura central dos doentes com objetivos terapêuticos pré-definidos, assumindo-se actualmente como uma mais-valia no tratamento clínico de vítimas com TCE. Objetivos – Avaliar a eficácia da HT intra-hospitalar na redução da morbilidade e mortalidade do adulto vítima de TCE. Métodos – Foi realizada uma revisão sistemática da literatura sobre a eficácia da HT intrahospitalar na redução da morbilidade e mortalidade do adulto vítima de TCE. Efetuou-se uma pesquisa na PUBMED, The Cochrane Library, Scielo e Google Académico de estudos publicados entre 1 de janeiro de 2012 a 31 de agosto de 2014. Partindo dos critérios de inclusão previamente definidos, os estudos selecionados foram posteriormente avaliados. Dois revisores avaliaram a qualidade dos estudos a incluir, utilizando a grelha para a avaliação crítica de um estudo de Ascenção et al. (2008). Resultados – Quatro artigos preencheram os critérios de inclusão, tendo-se constituído como corpus amostral. Como metasíntese e seleção da análise dos artigos, inferiu-se que os potenciais benefícios neuroprotetores da hipotermia terapêutica, sem efeitos colaterais negativos, deve ser implementada como parte do quotidiano de tratamento e controlo das vítimas de TCE e não como terapia de resgate. Contudo, a validação das implicações práticas da HT carece de mais estudos, cuja indução seja fator neuroprotetor, independentemente do valor da PIC, individualizando a duração da indução da hipotermia. Conclusão – Os benefícios da HT em adultos vítimas de TCE são ainda alvo de debate, requerendo a realização de mais metanálises e ensaios clínicos, visando a atualização das suas recomendações. Palavras-chave – Hipotermia terapêutica; traumatismo crânio-encefálico; eficácia

Erythropoietin protects against ischaemic acute renal injury

Erythropoietin (EPO) has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental brain injury and cisplatin-induced nephrotoxicity. The aim of the present study was to determine whether EPO administration is also renoprotectivein both in vitro and in vivo models ofischaemic acute renal failure Methods. Primary cultures of human proximal tubule cells (PTCs) were exposed to either vehicle or EPO (6.25–400 IU/ml) in the presence of hypoxia (1% O2), normoxia (21% O2) or hypoxia followed by normoxia for up to 24 h. The end-points evaluated included cell apoptosis (morphology and in situ end labelling [ISEL], viability [lactate dehydrogenase (LDH release)], cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA synthesis (thymidine incorporation). The effects of EPO pre-treatment (5000 U/kg) on renal morphology and function were also studied in rat models of unilateral and bilateral ischaemia–reperfusion (IR) injury. Results. In the in vitro model, hypoxia (1% O2) induced a significant degree of PTC apoptosis, which was substantially reduced by co-incubation with EPO at 24 h (vehicle 2.5±0.5% vs 25 IU/ml EPO 1.8±0.4% vs 200 IU/ml EPO 0.9±0.2%, n = 9, P

Simplest tasks have greatest dual task interference with balance in brain injured adults

Attention difficulties and poor balance are both common sequel following a brain injury. This study aimed to determine whether brain injured adults had greater difficulty than controls in performing a basic balance task while concurrently completing several different cognitive tasks varying in visuo-spatial attentional load and complexity. Twenty brain injured adults and 20 age-, sex- and education level-matched controls performed a balance-only task (step stance held for 30s), five cognitive-only tasks (simple and complex non-spatial, visuo-spatial, and a control articulation task), and both together (dual tasks). Brain injured adults showed a greater centre of pressure (COP) excursion and velocity in all conditions than controls. Brain injured adults also demonstrated greater interference with balance when concurrently performing two cognitive tasks than control subjects. These were the control articulation and the simple non-spatial task. It is likely that distractibility during these simple tasks contributed to an increase in COP motion and interference with postural stability in stance. Performing visuo-spatial tasks concurrently with the balance task did not result in any change in COP motion. Dual task interference in this group is thus unlikely to be due to structural interference. Similarly, as the more complex tasks did not uniformly result in increased interference, a reduction in attentional capacity in the brain injured population is unlikely to be the primary cause of dual task interference in this group. (C) 2004 Elsevier B.V. All rights reserved.

Dynamic classifiers for neonatal brain monitoring

Brain injury due to lack of oxygen or impaired blood flow around the time of birth, may cause long term neurological dysfunction or death in severe cases. The treatments need to be initiated as soon as possible and tailored according to the nature of the injury to achieve best outcomes. The Electroencephalogram (EEG) currently provides the best insight into neurological activities. However, its interpretation presents formidable challenge for the neurophsiologists. Moreover, such expertise is not widely available particularly around the clock in a typical busy Neonatal Intensive Care Unit (NICU). Therefore, an automated computerized system for detecting and grading the severity of brain injuries could be of great help for medical staff to diagnose and then initiate on-time treatments. In this study, automated systems for detection of neonatal seizures and grading the severity of Hypoxic-Ischemic Encephalopathy (HIE) using EEG and Heart Rate (HR) signals are presented. It is well known that there is a lot of contextual and temporal information present in the EEG and HR signals if examined at longer time scale. The systems developed in the past, exploited this information either at very early stage of the system without any intelligent block or at very later stage where presence of such information is much reduced. This work has particularly focused on the development of a system that can incorporate the contextual information at the middle (classifier) level. This is achieved by using dynamic classifiers that are able to process the sequences of feature vectors rather than only one feature vector at a time.

Impact of traumatic dental injuries and malocclusions on quality of life of young children

BACKGROUND The presence of traumatic dental injuries and malocclusions can have a negative impact on quality of life of young children and their parents, affecting their oral health and well-being. The aim of this study was to assess the impact of traumatic dental injuries and anterior malocclusion traits on the Oral Health-Related Quality of Life (OHRQoL) of children between 2 and 5 years-old. METHODS Parents of 260 children answered the six domains of the Early Childhood Oral Health Impact Scale (ECOHIS) on their perception of the OHRQoL (outcome). Two calibrated dentists assessed the types of traumatic dental injuries (Kappa = 0.9) and the presence of anterior malocclusion traits (Kappa = 1.0). OHRQoL was measured using the ECOHIS. Poisson regression was used to associate the type of traumatic dental injury and the presence of anterior malocclusion traits to the outcome. RESULTS The presence of anterior malocclusion traits did not show a negative impact on the overall OHRQoL mean or in each domain. Only complicated traumatic dental injuries showed a negative impact on the symptoms (p = 0.005), psychological (p = 0.029), self image/social interaction (p = 0.004) and family function (p = 0.018) domains and on the overall OHRQoL mean score (p = 0.002). The presence of complicated traumatic dental injuries showed an increased negative impact on the children's quality of life (RR = 1.89; 95% CI = 1.36, 2.63; p < 0.001). CONCLUSIONS Complicated traumatic dental injuries have a negative impact on the OHRQoL of preschool children and their parents, but anterior malocclusion traits do not.

2013-2017 State Plan on Brain Injuries - Progress Report, March 9, 2016

The 2013-2017 State Plan for Brain Injuries was developed by the Iowa Advisory Council on Brain Injuries (ACBI) as guidance for brain injury services and prevention activities in Iowa. The following outlines progress made on the plan’s goals from date of implementation through December 2015.

The influence of environmental distraction on cognitive abilities in ADL performance after frontal brain injured.

Background: Previous studies have reported errors in Activities of Daily Living (ADL) under the presence of distracting objects in dementia and brain injury patients. However, little is known about which distractor-target objects relation might be more harmful for performance. Method: We compared the ADL execution in frontal brain injured patients and control participants under two conditions: One in which target objects were mixed with distractor objects that constituted an alternative semantically related but non-required task (contextual condition) and another in which target objects were mixed with related but isolated distractors that did not constituted a coherent task (non-contextual condition). We separately analyzed ADL commission errors (repetitions, substitutions, objects manipulations, failures in sequence, extra actions) and omissions. In addition, the participants were evaluated with a neuropsychological protocol including a very specific executive functions task (Selective attention, Stimulus-Stimulus and Stimulus-Response conflict). Results: We found that frontal patients produced more commission errors compared to control participants, but only under the contextual condition. No between groups significant differences were found in omissions in both conditions or commission errors in non-contextual conditions. Scores in the Stimulus-Response conflict was significantly correlated with commission errors in the contextual condition. Conclusion: The presence of different non-target objects in ADL performance could require different cognitive process. Contextual ADL conditions required a higher level of executive functions, especially at the level of response (Stimulus-Response conflict). Application to Practice: Occupational therapists should control the presence of objects related to the target task according to the intervention objectives with the patients.

Polymeric implant of methylprednisolone for spinal injury: preparation and characterization

Purpose: To improve the effectiveness and reduce the systemic side effects of methylprednisolone in traumatic spinal injuries, its polymeric implants were prepared using chitosan and sodium alginate as the biocompatible polymers. Methods: Implants of methylprednisolone sodium succinate (MPSS) were prepared by molding the drug-loaded polymeric mass obtained after ionotropic gelation method. The prepared implants were evaluated for drug loading, in vitro drug release and in vivo performance in traumatic spinal-injury rat model with paraplegia. Results: All the implant formulations were light pale solid matrix with smooth texture. Implants showed 86.56 ± 2.07 % drug loading. Drug release was 89.29 ± 1.25 % at the end of 7 days. Motor function was evaluated in traumatic spinal injury-induced rats in terms of its movement on the horizontal bar. At the end of 7 days, the test group showed the activity score (4.75 ± 0.02) slightly higher than that of standard (4.62 ± 0.25), but the difference was not statistically different (p > 0.05). Conclusion: MPSS-loaded implants produces good recovery in traumatic spinal-injury rats.

Human congenital cytomegalovirus infection: characteristics and pathogenesis of fetal brain damage

Human cytomegalovirus (HCMV) causes congenital neurological lifelong disabilities. The study analyzed 10 HCMV-infected human fetuses at 21 weeks of gestation to evaluate the characteristics and pathogenesis of brain injury related to congenital human CMV (cCMV) infection. Specifically, tissues from cortical and white matter areas, subventricular zone, thalamus, hypothalamus, hippocampus, basal ganglia and cerebellum were analysed by: i) immunohistochemistry (IHC) to detect HCMV-infected cell distribution, ii) hematoxylin-eosin staining to evaluate histological damage and iii) real-time PCR to quantify tissue viral load (HCMV-DNA). Viral tropism was assessed by double IHC to detect HCMV-antigens and neural/neuronal markers: nestin (expressed in early differentiation stage), doublecortin (DCX, identifying neuronal precursor cells) and neuronal nuclei (NeuN, identifying mature neurons). HCMV-positive cells and viral DNA were found in the brain of 8/10 (80%) fetuses. For these cases, brain damage was classified in mild (n=4, 50%), moderate (n=3, 37.5%) and severe (n=1, 12.5%) based on presence of i) diffuse astrocytosis, microglial activation and vascular changes; ii) occasional (in mild) or multiple (in moderate/severe) microglial nodules and iii) necrosis (in severe). The highest median HCMV-DNA level was found in the hippocampus (212 copies/5ng of humanDNA [hDNA], range: 10-7,505) as well as the highest mean HCMV-infected cell value (2.9 cells, range: 0-23), followed by that detected in subventricular zone (1.8 cells, range: 0-19). This suggests a preferential HCMV tropism for immature neuronal cells, residing in these regions, confirmed by the detection of DCX and nestin in 94% and 63.3% of HCMV-positive cells, respectively. NeuN was not found among HCMV-positive cells and was nearly absent in the brain with severe damage, suggesting HCMV does not infect mature neurons and immature HCMV-infected neuronal cells do not differentiate into neurons. HCMV preferential tropism in immature neural/neuronal cells delays/inhibits their differentiation interfering with brain development processes that lead to structural and functional brain defects.

Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms

The present study investigated the role of ROS (reactive oxygen species) and COX (cyclooxygenase) in ethanol-induced contraction and elevation of [Ca(2+)](i) (intracellular [Ca(2+)]). Vascular reactivity experiments, using standard muscle bath procedures, showed that ethanol (1-800 mmol/l) induced contraction in endothelium-intact (EC(50): 306 +/- 34 mmol/l) and endothelium-denuded (EC(50): 180 +/- 40 mmol/l) rat aortic rings. Endothelial removal enhanced ethanol-induced contraction. Preincubation of intact rings with L-NAME [N(G)-nitro-L-arginine methyl ester; non-selective NOS (NO synthase) inhibitor, 100 mu mol/l], 7-nitroindazole [selective nNOS (neuronal NOS) inhibitor, 100 mu mol/l], oxyhaemoglobin (NO scavenger, 10 mu mol/l) and ODQ (selective inhibitor of guanylate cyclase enzyme, 1 mu mol/l) increased ethanol-induced contraction. Tiron [O(2)(-) (superoxide anion) scavenger, 1 mmol/l] and catalase (H(2)O(2) scavenger, 300 units/ml) reduced ethanol-induced contraction to a similar extent in both endothelium-intact and denuded rings. Similarly, indomethacin (non-selective COX inhibitor, 10 mu mol/l), SC560 (selective COX- I inhibitor, 1 mu mol/l), AH6809 [PGF(2 alpha) (prostaglandin F(2 alpha))] receptor antagonist, 10 mu mol/l] or SQ29584 [PGH(2)(prostaglandin H(2))/TXA(2) (thromboxane A(2)) receptor antagonist, 3 mu mol/l] inhibited ethanol-induced contraction in aortic rings with and without intact endothelium. In cultured aortic VSMCs (vascular smooth muscle cells), ethanol stimulated generation of O(2)(-) and H(2)O(2). Ethanol induced a transient increase in [Ca(2+)](i), which was significantly inhibited in VSMCs pre-exposed to tiron or indomethacin. Our data suggest that ethanol induces vasoconstriction via redox-sensitive and COX-dependent pathways, probably through direct effects on ROS production and Ca(2+) signalling. These findings identify putative molecular mechanisms whereby ethanol, at high concentrations, influences vascular reactivity. Whether similar phenomena occur in vivo at lower concentrations of ethanol remains unclear.

Quality of life and neuropsychological changes in mild head trauma - Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission

Introduction: mild head trauma (MHT) is defined as a transient neurological deficit after trauma with a history of impairment or loss of consciousness lasting less than 15 min and/or posttraumatic amnesia, and a Glasgow Coma Scale between 13 and 15 on hospital admission. We evaluated 50 MHT patients 18 months after the trauma, addressing signs and symptoms of post-concussion syndrome, quality of life and the presence of anxiety and depression. We correlate those findings with the S100B protein levels and cranial CT scan performed at hospital admission after the trauma. Method: patients were asked to fill out questionnaires to assess quality of life (SF36), anxiety and depression (HADS), and signs and symptoms of post-concussion syndrome. For the control group, we asked the patient`s household members, who had no history of head trauma of any type, to answer the same questionnaires for comparison. Results: total quality of life index for patients with MHT was 58.16 (+/-5), lower than the 73.47 (+/-4) presented by the control group. Twenty patients (55.2%) and four (11.1%) controls were depressed. Seventeen patients (47.2%) presented anxiety, whereas only eight (22.2%) controls were considered anxious. Victims of MHT complained more frequently of loss of balance, dry mouth, pain in the arms, loss of memory and dizziness than their respective controls (p < 0.05). We found no correlation between the presence of these signs and symptoms, quality of life, presence of anxiety and depression with S100B protein levels or with presence of injury in the cranial CT performed at hospital admission. Conclusion: MHT is associated with a higher incidence of post-concussion syndrome symptoms, lower quality of life and anxiety than their respective controls even 18 months after the trauma. (C) 2007 Elsevier Ltd. All rights reserved.

Egr transcription factors in the nervous system

The Egr proteins, Egr-1, Egr-2, Egr-3 and Egr-4, are closely related members of a subclass of immediate early gene-encoded, inducible transcription factors. They share a highly homologous DNA-binding domain which recognises an identical DNA response element. In addition, they have several less-well conserved structural features in common. As immediate early proteins, the Egr transcription factors are rapidly induced by diverse extracellular stimuli within the nervous system in a discretely controlled manner. The basal expression of the Egr proteins in the developing and adult rat brain and the induction of Egr proteins by neurotransmitter analogue stimulation, physiological mimetic and brain injury paradigms is reviewed. We review evidence indicating that Egr proteins are subject to tight differential control through diverse mechanisms at several levels of regulation. These include transcriptional, translational and posttranslational (including glycosylation, phosphorylation and redox) mechanisms and protein-protein interaction. Ultimately the differentially co-ordinated Egr response may lead to discrete effects on target gene expression. Some of the known target genes of Egr proteins and functions of the Egr proteins in different cell types are also highlighted. Future directions for research into the control and function of the different Egr proteins are also explored. (C) 1997 Elsevier Science Ltd.

Brazilian version of the Functional Assessment Measure: cross-cultural adaptation and reliability evaluation

The objective of this prospective study was to perform a cross-cultural adaptation of the Functional Assessment Measure (FAM) into Brazilian Portuguese, and to assess the test-retest reliability. The instrument was translated, back-translated, pretested, and reviewed by a committee. The Brazilian version was assessed in 61 brain-injury patients. Intrarater and interrater reliability was verified by a test-retest procedure (intraclass correlation). Intrarater reliability was moderate-to-excellent; interrater reliability was moderate-to-excellent, with the exception of one item. The Brazilian version of the FAM has acceptable test-retest reliability. Results suggest the use of the Brazilian version of the FAM in the Brazilian population, for disability evaluation and outcome assessment. Further research is required to evaluate the psychometric properties of the scale. International Journal of Rehabilitation Research 34:89-91 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Long-Term Astroglial Reaction and Neuronal Plasticity in the Subcortical Visual Pathways After a Complete Ablation of Telencephalon in Pigeons (Columba livia)

This paper analyzes the astroglial and neuronal responses in subtelencephalic structures, following a bilateral ablation of the telencephalon in the Columba livia pigeons. Control birds received a sham operation. Four months later the birds were sacrificed and their brains processed for glial fribillary acid protein (GFAP) and neurofilament immunohistochemistry, markers for astrocytes and neurons, respectively. Computer-assisted image analysis was employed for quantification of the immunoreactive labeling in the nucleus rotundus (N.Rt) and the optic tectum (OT) of the birds. An increased number of GFAP immunoreactive astrocytes were found in several subregions of the N.Rt (p .001), as well as in layers 1, 2cd, 3, and 6 of the OT (p .001) of the lesioned animals. Neurofilament immunoreactivity decreased massively in the entire N.Rt of the lesioned birds; however, remaining neurons with healthy aspect showing large cytoplasm and ramified branches were detected mainly in the periphery of the nucleus. In view of the recently described paracrine neurotrophic properties of the activated astrocytes, the data of the present study may suggest a long-lasting neuroglial interaction in regions of the lesioned bird brain far from injury. Such events may trigger neuronal plasticity in remaining brain structures that may lead spontaneous behavior recovery as the one promoted here even after a massive injury.

Influence of treadmill training on motor performance and organization of exploratory behavior in Meriones unguiculatus with unilateral ischemic stroke: Histological correlates in hippocampal CA1 region and the neostriatum

This study examined the effects of motor stimulation via treadmill on the behavior of male gerbils after external carotid ischemic brain lesion. The animals were assigned to five groups; ischemic with no stimulation (SIG), ischemic with stimulation (SIG 12/24/48/72 It after surgery), non-ischemic with no stimulation (CC), non-ischemic with stimulation (CE) and sham, surgery without occlusion with no stimulation (SH). All the animals were tested in the open-field (OF) and rotarod (RR), 4 days after surgery in order to evaluate exploratory behaviors and motor performance. Data were submitted to one-way variance (ANOVA) and Dunnett`s post hoc comparisons. SIG and SIG 12 groups showed a significant decrease in motor response (crossing) when compared to the control group (CC) (F = 20.65, P < 0.05) in the OF. SIG 12 group showed an increase in grooming behavior (F = 23.136, P < 0.05) and all ischemia groups (SIG, SIG 12/24/48/72) spent less time on the RR (F = 10.40, P < 0.05), when compared to the control group (CC). Histological analyses show extensive lesions in the hippocampus and neostriatum for all groups with ischemia (SIG, SIG 12/24/48/72), which are structures involved in the organization of motor behavior. Interestingly, the most pronounced damage was found in animals submitted to motor stimulation 12 h after ischemia which can be correlated to the increased number of grooming behavior showed by them in the OF. These findings suggest that motor stimulation through treadmill training improve motor behavior after ischemia, except when it starts 12h after surgery. (c) 2007 Elsevier Ireland Ltd. All rights reserved.