Resveratrol Reduces Neuroinflammation and Hippocampal Microglia Activation and Protects Against Impairment of Memory and Anxiety-Like Behavior in Experimental Cerebral Palsy.

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by motor and postural impairments. However, early brain injury can promote deleterious effects on the hippocampus, impairing memory. This study aims to investigate the effects of resveratrol treatment on memory, anxiety-like behavior, and neuroinflammation markers in rats with CP. Male Wistar rats were subjected to perinatal anoxia (P0-P1) and sensory-motor restriction (P2-P28). They were treated with resveratrol (10 mg/kg, 0.1 ml/100 g) or saline from P3-P21, being divided into four experimental groups: CS (n = 15), CR (n = 15), CPS (n = 15), and CPR (n = 15). They were evaluated in the tests of novel object recognition (NORT), T-Maze, Light-Dark Box (LDB), and Elevated Plus Maze (EPM). Compared to the CS group, the CPS group has demonstrated a reduced discrimination index on the NORT (p < 0.0001) and alternation on the T-Maze (p < 0.01). In addition, the CPS group showed an increase in permanence time on the dark side in LDB (p < 0.0001) and on the close arms of the EPM (p < 0.001). The CPR group demonstrated an increase in the object discrimination index (p < 0.001), on the alternation (p < 0.001), on the permanence time on the light side (p < 0.0001), and on the open arms (p < 0.001). The CPR group showed a reduction in gene expression of IL-6 (p = 0.0175) and TNF-α (p = 0.0007) and an increase in Creb-1 levels (p = 0.0020). The CPS group showed an increase in the activated microglia and a reduction in cell proliferation in the hippocampus, while CPR animals showed a reduction of activated microglia and an increase in cell proliferation. These results demonstrate promising effects of resveratrol in cerebral palsy behavior impairment through reduced neuroinflammation in the hippocampus.

Neonatal treatment with resveratrol decreases postural and strength impairments and improves mitochondrial function in the somatosensory cortex rats submitted to cerebral palsy.

Cerebral palsy is a neurodevelopmental disease characterized by postural, motor, and cognitive disorders, being one of the main causes of physical and intellectual disability in childhood. To minimize functional impairments, the use of resveratrol as a therapeutic strategy is highlighted due to its neuroprotective and antioxidant effects in different regions of the brain. Thus, this study aimed to investigate the effects of neonatal treatment with resveratrol on postural development, motor function, oxidative balance, and mitochondrial biogenesis in the brain of rats submitted to a cerebral palsy model. Neonatal treatment with resveratrol attenuated deficits in somatic growth, postural development, and muscle strength in rats submitted to cerebral palsy. Related to oxidative balance, resveratrol in cerebral palsy decreased the levels of MDA and carbonyls. Related to mitochondrial biogenesis, was observed in animals with cerebral palsy treated with resveratrol, an increase in mRNA levels of TFAM, in association with the increase of citrate synthase activity. The data demonstrated a promising effect of neonatal resveratrol treatment, improving postural and muscle deficits induced by cerebral palsy. These findings were associated with improvements in oxidative balance and mitochondrial biogenesis in the brain of rats submitted to cerebral palsy.

Therapeutic advances for treating memory impairments in perinatal brain injuries with implications for cerebral palsy: a systematic review and meta-analysis of preclinical studies.

Cerebral palsy (CP) is a neurodevelopmental disorder caused by damage to the immature brain. CP is considered the main cause of physical disability in childhood. Studies have shown that memory function and emotional behaviour are significantly impaired in CP. Current thought is that interventions for neuromotor damaged play a prominent role, but neglects the memory acquisition problems that affect the functioning and quality of life of these children. This systematic review aims to map and analyse pre-clinical interventions used to treat memory formation problems resulting from CP. For this, a search was carried out in the Pubmed, Web of Science, Scopus and Lilacs databases. Then, eligibility, extraction date and evaluation of the methodological quality of the studies were determined. 52 studies were included in this review, and 27 were included in a meta-analysis. Assessing memory performance as a primary outcome, and structural and biochemical changes in the hippocampus as a secondary outcome. CP models were reported to be induced by hypoxia-ischemia, oxygen deprivation and liposaccharide (LPS) exposure, resulting in impairments in the formation of short-term and long-term memory in adult life. A reduction in escape latency and dwell time were observed in the target quadrant as well as an increase in the time needed for the rodents to find the platform in the Morris Water Maze (MWM). Brain injuries during the perinatal period are considered an insult that negatively impacts hippocampus maturation and causes impairment in memory formation in adult life. Some studies reported that regions of the hippocampus such as the dentate gyrus and cornu ammonis 1 were impaired in CP, noting an increase in oxidative stress enzymes and pro-inflammatory cytokines, associated with a reduction in BDNF and neurogenesis levels. These were reported to cause a reduction in the number of neurons and the volume of the hippocampus, in addition to an increase in astrogliosis and apoptosis of neurons and difficulties in forming new memories similar to those that occur in children with CP. Interventions that reduced neuroinflammation and the presence of free radicals were highlighted as a therapy for the memory disturbance present in CP. Preclinical studies registered treatments with oxygen interventions, resveratrol and erythropoietin, which were able to reduce the damage to the hippocampus and promote improvements in memory and behaviour. In the meta-analysis of selected studies, we observed favorable results, through effect size, for the use of oxygen interventions (SDM -6.83 95% CI [-7.91, -5.75], Z = 12.38, p = 0.03; I2 = 71%), erythropoietin (SDM -3.16 95% CI [-4.27, -2.05], Z = 5.58, p = 0.002; I2 = 82%) and resveratrol (SDM -2.42 95% CI [-3.19, - 1.66], Z = 6.21, p = 0.01; I2 = 77%), stimulating plastic responses in the hippocampus and facilitating the memory formation, with these presenting positive effects in general (SDM -2.84 95% CI [-3.10, -2.59], Z = 22.00; p < 0.00001; I2 = 92.9%). These studies demonstrate possible avenues of intervention for memory alterations in experimental models of early brain injuries, highlighting promising interventions that can facilitate the maturation of the hippocampus and memory formation and, consequently, minimize functional problems that arise during development.

Locomotion is impacted differently according to the perinatal brain injury model: Meta-analysis of preclinical studies with implications for cerebral palsy.

BACKGROUND: Different approaches to reproduce cerebral palsy (CP) in animals, contribute to the knowledge of the pathophysiological mechanism of this disease and provide a basis for the development of intervention strategies. Locomotion and coordination are the main cause of disability in CP, however, few studies highlight the quantitative differences of CP models, on locomotion parameters, considering the methodologies to cause brain lesions in the perinatal period. METHODS: Studies with cerebral palsy animal models that assess locomotion parameters were systematically retrieved from Medline/PubMed, SCOPUS, LILACS, and Web of Science. Methodological evaluation of included studies and quantitative assessment of locomotion parameters were performed after eligibility screening. RESULTS: CP models were induced by hypoxia-ischemia (HI), Prenatal ischemia (PI), lipopolysaccharide inflammation (LPS), intraventricular haemorrhage (IVH), anoxia (A), sensorimotor restriction (SR), and a combination of different models. Overall, 63 studies included in qualitative synthesis showed a moderate quality of evidence. 16 studies were included in the quantitative meta-analysis. Significant reduction was observed in models that combined LPS with HI related to distance traveled (SMD -7.24 95 % CI [-8.98, -5.51], Z = 1.18, p < 0.00001) and LPS with HI or anoxia with sensory-motor restriction (SMD -6.01, 95 % CI [-7.67, -4.35], Z = 7.11), or IVH (SMD -4.91, 95 % CI [-5.84, -3.98], Z = 10.31, p < 0.00001) related to motor coordination. CONCLUSION: The combination of different approaches to reproduce CP in animals causes greater deficits in locomotion and motor coordination from the early stages of life to adulthood. These findings contribute to methodological refinement, reduction, and replacement in animal experimentation, favoring translational purposes.

Perfil clínico-epidemiológico de vítimas de traumatismo torácico submetidas a tratamento cirúrgico em um hospital de referência / Clinical and epidemiological profile of victims of chest trauma undergoingsurgical treatment at a referral hospital

Objetivos: Descrever o perfil clínico-epidemiológico de vítimas de traumatismo torácico submetidas a tratamento cirúrgico em um hospital de referência em trauma.Métodos: Um estudo epidemiológico transversal analisou os prontuários de todos os pacientes admitidos por traumatismo torácico e submetidos a tratamento cirúrgico entre agosto e novembro de 2011 no Hospital de Urgências de Goiânia.Resultados: Fizeram parte do estudo 89 (89%) homens e 11 (11%) mulheres, a maioria entre 20 e 39 anos (49%). Os ferimentos por arma branca (57,9%) e o hemopneumotórax (45,6%) foram mais frequentes no trauma torácico aberto e os acidentes motociclísticos (62,8%) e o hemotórax (48,8%) mais frequentes no fechado. O raio-x (69%) e a drenagem torácica unilateral (78%) foram os principais meios de diagnóstico e tratamento. Entre os pacientes com trauma torácico aberto, 11 (19,3%) necessitaram de toracotomia; destes, 36,3% apresentavam lesões pulmonares. Grande parte dos pacientes (48%) ficaram internados entre três e quatro dias. A taxa de mortalidade foi de 11%.Conclusões: O perfil das vítimas de trauma torácico que necessitaram de atendimento cirúrgico corresponde principalmente a homens jovens, com lesão decorrente de ferimento por arma branca ou de acidente motociclístico, apresentando hemopneumotórax ou hemotórax. Na maioria dos casos essas lesões foram diagnosticadas por raios-x e tratadas com drenagem torácica fechada. A maior parte dos pacientes teve boa evolução, com tempo de internação curto seguido da alta hospitalar. Estas informações podem auxiliar na organização do atendimento hospitalar de urgência e na implementação de medidas preventivas e de conscientização.

Aims: To describe the clinical and epidemiological profile of victims of chest trauma undergoing surgical treatment at a referral hospital for trauma.Methods: A cross-sectional epidemiological study analysed medical records of all patients admitted with chest trauma and underwent surgery between August and November 2011 in Emergency Hospital of Goiânia.Results: Participants were 89 (89%) men and 11 (11%) women, most between 20 and 39 years (49%). The stab wounds (57.9%) and hemopneumothorax (45.6%) were more frequent in open chest injury and motorcycle accidents (62.8%), and hemothorax (48.8%) was more frequent in blunt trauma. The x-ray (69%) and unilateral chest tube drainage (78%) were the main means of diagnosis and treatment. Among patients with open chest trauma, 11 (19.3%) required thoracotomy and of these, 36.3% had lung lesions. Most patients (48%) were hospitalized for three to four days. The mortality rate was 11%.Conclusions: The profile of victims of chest trauma requiring surgical care consisted mainly of young men with injuries caused by stab wound or motorcycle accidents, presenting hemopneumothorax or hemothorax. In most cases these lesions were diagnosed by x-rays and treated with closed drainage. Most patients had a good outcome, with shorter hospitalization?s time followed by hospital discharge. This information can assist in the organization of emergency hospital care as well as in the implementation of preventive measures and awareness.