RESUMO
After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Masculino , Feminino , Estudos Longitudinais , China/epidemiologia , SARS-CoV-2/classificação , SARS-CoV-2/fisiologia , Anticorpos Neutralizantes , Cinética , Anticorpos Antivirais/sangue , Reinfecção/epidemiologiaRESUMO
The medicinal Dendrobium species of Orchidaceae possess significant pharmaceutical value, and modern pharmacological research has shown that Dendrobium contains many important active ingredients. Alkaloids, the crucial components of medicinal Dendrobium, demonstrate beneficial healing properties in cardiovascular, cataract, gastrointestinal, and respiratory diseases. Members of the cytochrome P450 monooxygenase (CYP) gene family play essential roles in alkaloid synthesis, participating in alkaloid terpene skeleton construction and subsequent modifications. Although studies of the CYP family have been conducted in some species, genome-wide characterization and systematic analysis of the CYP family in medicinal Dendrobium remain underexplored. In this study, we identified CYP gene family members in the genomes of four medicinal Dendrobium species recorded in the Pharmacopoeia: D. nobile, D. chrysotoxum, D. catenatum, and D. huoshanense. Further, we analyzed the motif composition, gene replication events, and selection pressure of this family. Syntenic analysis revealed that members of the clan 710 were present on chromosome 18 in three medicinal Dendrobium species, except for D. nobile, indicating a loss of clan 710 occurring in D. nobile. We also conducted an initial screening of the CYP genes involved in alkaloid synthesis through transcriptome sequencing. Quantitative real-time reverse transcription PCR showed that the expression of DnoNew43 and DnoNew50, homologs of secologanin synthase involved in the alkaloid synthesis pathway, was significantly higher in the stems than in the leaves. This result coincided with the distribution of dendrobine content in Dendrobium stems and leaves, indicating that these two genes might be involved in the dendrobine synthesis pathway. Our results give insights into the CYP gene family evolution analysis in four medicinal Dendrobium species for the first time and identify two related genes that may be involved in alkaloid synthesis, providing a valuable resource for further investigations into alkaloid synthesis pathway in Dendrobium and other medicinal plants.
Assuntos
Alcaloides , Dendrobium , Dendrobium/genética , Alcaloides/genética , Alcaloides/análise , Vias Biossintéticas/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Terpenos/metabolismoRESUMO
Traumatic subdural effusion (TSE) is one of the main associated complications of brain trauma. About half of the asymptomatic TSEs ultimately evolve into chronic subdural hematomas (CSDHs), most of which will be inevitably treated by surgical evacuation. With the emergence of subdural hydroma (SDH), rupture of bridge-veins, bleeding of the hydroma wall, hyperfunction of fibrinolysis and increasing protein content in the hydroma are some of the traditionally cited explanations of the pathogenesis of TSE evolving into CSHD. Despite intensive research and subsequent advances in surgical techniques of CSDH, a single treatment with measurable clinical impact on the evolution interruption has yet to be investigated. Compared with peripheral venous blood, inflammatory cytokines were elevated in TSE and CSDH demonstrated by a number of investigators. Neoformation of capillaries, vascular hyper-permeability, serum protein exudation and other characteristics of aseptic inflammatory reaction were observed. Meanwhile, steroid was applied to treat CSDH in several groups, which was generally used as an effective anti-inflammatory agent. Based on systemic thinking, we hypothesize that TSE and CSDH are different stages, with different appearances, of the same inflammatory reaction. The evolution from TSE into CSDH and propagation of CSDH seem to be the results of local aseptic inflammation. Our hypothesis holds potential as a target for therapeutic intervention.
Assuntos
Lesões Encefálicas/complicações , Hematoma Subdural Crônico/etiologia , Inflamação , Modelos Neurológicos , Derrame Subdural/complicações , Humanos , Derrame Subdural/etiologiaRESUMO
To compare the effect of long-term mild hypothermia versus short-term mild hypothermia on the outcome of 215 severe traumatic brain injured patients with cerebral contusion and intracranial hypertension. At three medical centers, 215 patients aged 18 to 45 years old with an admission Glasgow Coma Scale < or =8 within 4 h after injury were randomly divided into two groups: long-term mild hypothermia group (n = 108) for 5+/-1.3 days mild hypothermia therapy and short-term mild hypothermia group (n = 107) for 2+/-0.6 days mild hypothermia therapy. All patients had intracranial hypertension and frontotemporoparietal contusion with midline shift >1 cm confirmed on computed tomographic scan. Glasgow Outcome Scale at 6-month follow-up, 47 cases had favorable outcome (43.5%), and other 61 cases had unfavorable outcome (56.5%) in the long-term mild hypothermia group. However, only 31 cases had favorable outcome (29.0%), and other 76 cases had unfavorable outcome (71.0%) in the short-term mild hypothermia group (P < 0.05). The intracranial pressure significantly rebounded after rewarming in the short-term mild hypothermia group, but not in the long-term mild hypothermia (P < 0.05). Furthermore, the incidence of stress ulcer, epilepsy, pulmonary infection, intracranial infection did not significantly differ between the two groups (P > 0.05). Compared with short-term mild hypothermia, long-term mild hypothermia significantly improves the outcome of severe traumatic brain injured patients with cerebral contusion and intracranial hypertension without significant complications. Our data suggest that 5 days of long-term cooling is more efficacious than 2 days of short-term cooling when mild hypothermia is used to control refractory intracranial hypertension in patients with severe traumatic brain injury.
Assuntos
Lesões Encefálicas/terapia , Hipotermia Induzida , Adolescente , Adulto , Lesões Encefálicas/complicações , Feminino , Escala de Resultado de Glasgow , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/terapia , Masculino , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do TratamentoRESUMO
Hypothermia has been demonstrated to protect the brain from ischemia or traumatic brain injury. Achieving profound hypothermia has relied on techniques requiring total body cooling, which may result in serious cardiovascular and pulmonary complications. A technique to selectively cool the brain could conceivably exert a marked protection on cerebral structures and provide a relatively bloodless operative surgical field without systemic complications. Accordingly, this approach was tried in 7 rhesus monkeys after induction of general anesthesia. The right internal carotid artery and both internal jugular veins were each occlusively cannulated and connected to a circulation pump. The left internal carotid artery, both external carotid arteries, and both external jugular veins were temporarily clamped to establish severe cerebral ischemia. Using a closed-circuit system, cooled Ringer's lactate liquid (4 degrees C) was infused through right internal carotid artery with outflow draining though both internal jugular veins. Cooled perfusate decreased cerebral temperature to the target temperature of 15 degrees C. Thereafter, pump flow was discontinued, and brains were rewarmed spontaneously, while the temporarily clamped carotid arteries and jugular veins were opened to resume normal cerebral blood circulation. Neurological functions were recorded daily and cerebral histology was examined at the conclusion of the experiment. Magnetic resonance (MR) scans were routinely taken before and 3 weeks after ischemia. In the normothermia control group of five rhesus monkeys, Ringer's solution at 37 degrees C was infused in the same manner as the cold solution with cerebral temperature maintained at 36.7 +/- 0.32 degrees C. Right cerebral temperature decreased from 36.5 +/- 0.49 to 15.5 +/- 2.29 degrees C, and simultaneously the left cerebral temperature decreased from 36.4 +/- 0.38 to 16.3 +/- 2.4 degrees C for 62.8 +/- 9.76 min during selective cerebral cooled Ringer's liquid perfusion. In contrast, rectal temperature was only reduced to 32.4 +/- 0.96 degrees C from a baseline of 37.2 +/- 0.76 degrees C. Internal jugular vein hematocrit was 38.2 +/- 0.31% before perfusion and 2.82 +/- 0.46% at the end of perfusion in profound hypothermia group; hematocrit was 39.7 +/- 0.62% before perfusion and 3.42 +/- 0.38% at the end of perfusion in the normothermia group. In the hypothermic group, neurological functions were normal during 6 months of follow-up, and microscopic examination of brain tissue did not show evidence of pathological changes in hippocampus or medulla. MR scans did not show any cerebral infarction. In contrast, none of the monkeys in normothermia group survived for more than several hours, and microscopic examination of the brain revealed extensive neuronal necrosis within the medulla. Selective cerebral profound hypothermia provides significant histologic and neurologic protection after severe cerebral ischemia. In addition, there were no major complications, and the operative field remained relatively bloodless in the profound hypothermic group.
Assuntos
Isquemia Encefálica/prevenção & controle , Hipotermia Induzida/métodos , Soluções Isotônicas/administração & dosagem , Anestesia Geral , Animais , Temperatura Corporal , Isquemia Encefálica/patologia , Artéria Carótida Interna , Temperatura Baixa , Circulação Extracorpórea , Infusões Intra-Arteriais , Macaca mulatta , Lactato de RingerRESUMO
BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.
Assuntos
Lesões Encefálicas/terapia , Respiração Artificial , Adulto , Idoso , Lesões Encefálicas Traumáticas/terapia , China , Estudos Transversais , Feminino , Humanos , Hipóxia-Isquemia Encefálica/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/terapia , Inquéritos e QuestionáriosRESUMO
A microbial consortium having a high capacity for rapid decolorization of azo dye (RED RBN) was immobilized by a phosphorylated polyvinyl alcohol (PVA) gel. The immobilized-cell beads exhibited a color removal capability of 75%, even at a high concentration of RED RBN (500 mg l(-1)) within 12 h using flask culture. The continuous operation was conducted at a hydraulic retention time (HRT) of 5-20 h in which the dye loading rate ranged from 240 to 60 mg dye h(-1). A removal efficiency exceeding 90% was obtained at the HRT higher than 10 h. No recognizable destruction of bead appearance was observed in the 6-month operation. Examination of the mechanism of the decolorization process by cell beads indicated that it proceeded primarily by biological decolorization associated with partial adsorption of the dye onto the entrapped cells and gel matrix. Microscopic observation revealed that the microbial consortium contained in the gel beads was at least made up of three kinds of bacterial species. From the economical viewpoint, alternative cheaper nitrogen sources such as fish meal, soybean meal, pharmamedia and vita yeast powder were examined.
Assuntos
Compostos Azo/metabolismo , Bactérias Aeróbias/metabolismo , Reatores Biológicos/microbiologia , Cor , Corantes/metabolismo , Esgotos/microbiologia , Bactérias Aeróbias/citologia , Biodegradação Ambiental , Células Imobilizadas/metabolismo , Colorimetria/métodos , Estudos de Viabilidade , Resíduos Industriais/prevenção & controle , Microesferas , Projetos Piloto , Álcool de Polivinil , Controle de Qualidade , Poluentes Químicos da Água/metabolismoRESUMO
OBJECTIVE: To determine the effect of arousal methods for prolonged coma of 175 patients with severe traumatic brain injury and related factors. METHODS: There were 175 cases with persistent coma longer than 1 month after severe traumatic brain injury. Coma lasted 1-12 months. Arousal procedures included hyperbaric oxygen, physical therapy and arousal drugs. RESULTS: In the 175 prolonged coma patients 110 got recovery of consciousness; in 118 cases with coma of 1-3 months, 86 cases recovered consciousness (72.9%); in 42 cases with coma of 4-6 months, 20 cases recovered consciousness (47.6); and in 15 cases with coma of longer than 6 months, only 4 cases recovered consciousness (26.7%). The recovery of consciousness depended on patient's primary brain stem damage, cerebral hernia, GCS score, and age. CONCLUSIONS: Application of appropriate arousal procedures improves recovery of consciousness in patients with prolonged coma.
Assuntos
Lesões Encefálicas/terapia , Coma Pós-Traumatismo da Cabeça/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
Here we investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. We began with 210 adult male Sprague-Dawley rats and randomly assigned them to three groups: TBI with hypothermia treatment (32°C), TBI with normothermia (37°C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. Mild hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. The rats were killed at 4, 6, 12, 24, 48, and 72 h and 1 week after TBI. The mRNA and protein level of TIMP-3 in both the injured and uninjured hemispheres of the brains from each group were measured using RT-PCR and Western blotting. In the normothermic group, TIMP-3 levels in both the injured and uninjured hemispheres were significantly increased after TBI compared with those of sham-injured animals (p < 0.01). In contrast, post-traumatic hypothermia significantly attenuated this increase. According to the RT-PCR and Western blot analyses, the maximum mRNA levels of TIMP-3 were reduced to 60.60 ± 2.30%, 55.83 ± 1.80%, 66.03 ± 2.10%, and 64.51 ± 1.50%, respectively, of the corresponding values in the normothermic group in the injured and uninjured hemispheres (cortex and hippocampus) of the hypothermia group (p < 0.01), while the respective maximum protein levels of TIMP-3 were reduced to 57.50 ± 1.50, 52.67 ± 2.20, 60.31 ± 2.50 and 54.76 ± 1.40 (p < 0.01). Our data suggest that moderate fluid percussion brain injury significantly upregulates TIMP-3 expression, and that this increase may be suppressed by hypothermia treatment.
Assuntos
Lesões Encefálicas/metabolismo , Hipotermia Induzida , Inibidor Tecidual de Metaloproteinase-3/biossíntese , Animais , Western Blotting , Temperatura Corporal/fisiologia , Lesões Encefálicas/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Lateralidade Funcional/fisiologia , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Inibidor Tecidual de Metaloproteinase-3/genéticaRESUMO
In this study, we explored the effect of moderate hypothermia on brain tissue oxygenation following acute intracranial hypertension in micropigs. Twenty healthy juvenile micropigs weighting 4-6 kg were randomized into two groups: a normothermia group (n = 10) and a moderate hypothermia group (n = 10). The animals were intravenously anesthetized with propofol (4 mg/kg), an endotracheal tube was inserted, and mechanical ventilation was begun. Autologous arterial blood was injected into the left frontal lobe to establish acute intracerebral hematoma and intracranial hypertension (intracranial pressure [ICP] >40 mm Hg) in all animals. Cooling was initiated at 30 min after injection of the blood, and was achieved via the use of an ice bath and ice packs. In the hypothermia group, the brain temperature decreased to 33-34 degrees C. Brain temperature was maintained at 37 +/- 0.3 degrees C in the normothermia group. The ICP, cerebral perfusion pressure (CPP), brain tissue oxygen pressure (P(br)O(2)), brain tissue carbon dioxide pressure (P(br)CO(2)), and brain tissue pH value (pH(br)) were continuously monitored for 3 h in all animals. Compared to normothermia group, ICP values significantly decreased and CPP markedly improved in the hypothermia group (p < 0.05). Further, pH(br) also markedly increased and P(br)CO(2) decreased significantly in the hypothermia group (p < 0.05). However, P(br)O(2) did not statistically significantly improve in the hypothermia group (p > 0.05). In sum, moderate hypothermia significantly decreased ICP, reduced P(br)CO(2), and increased pH(br) values, but did not improve cerebral oxygenation following acute intracranial hypertension.
Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Hipotermia Induzida , Hipertensão Intracraniana/terapia , Animais , Encéfalo/patologia , Hipertensão Intracraniana/metabolismo , Hipertensão Intracraniana/patologia , SuínosRESUMO
BACKGROUND: Traumatic brain injury (TBI), a major cause of morbidity and mortality, is a serious public health concern. OBJECTIVE: To evaluate the effect of mild hypothermia on gene expression in the hippocampus and to try to elucidate molecular mechanisms of hypothermic neuroprotection after TBI. METHODS: Rats were subjected to mild hypothermia (group 1: n = 3, 33 degrees C, 3H) or normothermia (group 2: n = 3; 37 degrees C, 3H) after TBI. Six genome arrays were applied to detect the gene expression profiles of ipsilateral hippocampus. Functional clustering and gene ontology analysis were then carried out. Another 20 rats were randomly assigned to 4 groups (n = 5 per group): group 3, sham-normothermia; group 4, sham-hypothermia; group 5, TBI-normothermia; and group 6, TBI-hypothermia. Real-time fluorescent quantitative reverse-transcription polymerase chain reaction was used to detect specific selected genes. RESULTS: We found that 133 transcripts in the hypothermia group were statistically different from those in the normothermia group, including 57 transcripts that were upregulated and 76 that were downregulated after TBI (P < .01). Most of these genes were involved in various pathophysiological processes, and some were critical to cell survival. Analysis showed that 9 gene ontology categories were significantly affected by hypothermia, including the most affected categories: synapse organization and biogenesis (upregulated) and regulation of inflammatory response (downregulated). The mRNA expression of Ank3, Cmbp, Nrxn3, Tgm2, and Fcgr3 was regulated by hypothermia, TBI, or a combination of TBI and hypothermia compared with the sham-normothermia group. Their mRNA expression was significantly regulated by hypothermia in TBI groups. CONCLUSION: Posttraumatic mild hypothermia has a significant effect on the gene expression profiles of the hippocampus, especially those genes belonging to the 9 gene ontology categories. Differential expression of those genes may be involved in the most fundamental molecular mechanisms of cerebral protection by mild hypothermia after TBI.
Assuntos
Lesões Encefálicas/genética , Lesões Encefálicas/terapia , Regulação da Expressão Gênica/fisiologia , Hipocampo/metabolismo , Hipotermia Induzida/métodos , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Animais , Lesões Encefálicas/fisiopatologia , Modelos Animais de Doenças , Genômica/métodos , Hipocampo/fisiopatologia , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Abstract In this study we retrospectively analyzed the outcome of bilateral decompressive craniectomy (BDC) for 37 patients with bilateral malignant diffuse brain swelling following severe traumatic brain injury (TBI). Our 37 patients (Glasgow Coma Scale [GCS] score =8) were retrospectively analyzed from September 2005 through September 2008. All patients underwent bilateral frontotemporoparietal decompressive craniectomy followed by duraplasty. The intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were measured before and after BDC, and Glasgow Outcome Scale (GOS) scores were measured after >6 months of follow-up. The mean ICP was 37.7 +/- 6.4 mm Hg, and the mean CPP was 57.6 +/- 7.5 mm Hg before BDC. The ICP significantly decreased to 27.4 +/- 7.2 mm Hg (p < 0.05) after bone removal, and the CPP significantly increased to 63.3 +/- 8.4 mm Hg (p < 0.05). The ICP had a larger decrease, to 11.2 +/- 7.1 mm Hg (p < 0.05), after opening and enlargement of the dura mater (p < 0.05) compared to the levels seen after bone removal, and CPP significantly increased to 77.8 +/- 8.3 mm Hg (p < 0.05). After surgery, the ICP was elevated, but remained lower than the initial ICP (p < 0.05), and was easily controlled by routine medical treatment in the ensuing days, and the CPP remained above the optimal threshold of 70 mm Hg. The mean follow-up time was 9.4 +/- 3.2 months. In total, 20 patients (54.1%) had favorable outcomes, including 12 patients (32.5%; GOS 4) with moderate deficits, and 8 patients (21.6%; GOS 5) showed good recovery and social reintegration. Also, 17 patients (45.9%) had unfavorable outcomes, including 7 patients (18.9%; GOS 1) who died, 4 patients (10.8%; GOS 2) remained in a vegetative state, and 6 patients (16.2%; GOS 3) had severe deficits. The most common complication was hydrocephalus (7 patients, 18.9%). Our data show that BDC offers immediate reductions in intracranial hypertension, and perhaps contributes to satisfactory outcomes in patients with bilateral diffuse brain swelling following severe TBI.
Assuntos
Edema Encefálico/cirurgia , Lesões Encefálicas/cirurgia , Craniectomia Descompressiva/métodos , Hipertensão Intracraniana/cirurgia , Adolescente , Adulto , Idoso , Edema Encefálico/etiologia , Lesões Encefálicas/complicações , Craniectomia Descompressiva/efeitos adversos , Feminino , Escala de Coma de Glasgow , Humanos , Hidrocefalia/etiologia , Hipertensão Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The temporal and regional expression profiles of matrix metalloproteinase-9 (MMP-9), after moderate or severe traumatic brain injury (TBI) were measured to investigate the effects of post-traumatic hypothermia (33 degrees C) or hyperthermia (39 degrees C). In the first phase of this study, adult male Sprague-Dawley rats were randomly assigned to groups of moderate TBI (1.8-2.2 atm), severe TBI (2.4-2.7 atm), and sham-injured control. The rats were killed at 4, 6, 12, 24, 48, and 72 h, or 1 week after TBI, for mRNA and protein analysis. In the second phase, rats underwent moderate fluid percussion brain injury, followed immediately by 4 h of post-traumatic normothermia (37 degrees C), hyperthermia (39 degrees C), or hypothermia (32 degrees C). The rats were killed at 12 and 48 h after TBI for mRNA expression analyses, or killed at 24 and 72 h after TBI for protein expression analyses. Brain samples, including the cerebral cortex and hippocampus (both ipsilateral and contralateral hemispheres of each group), were assayed using RT-PCR and Western blot techniques. MMP-9 levels in both the ipsilateral and contralateral hemispheres were significantly increased after TBI compared with those of sham injured animals (p < 0.01). Two expression peaks of MMP-9 were observed in the ipsilateral cortex and hippocampus. An increase in injury severity was associated with an increase in mRNA (12 and 48 h), and protein (24 and 72 h) levels of MMP-9. Post-traumatic hypothermia attenuated the increase in both the mRNA and protein levels of MMP-9, compared with normothermia and hyperthermia (p < 0.01). In contrast, hyperthermia had no significant effect on mRNA (at 12 h) and protein levels (at 24 h) of MMP-9, compared with normothermic values (p > 0.05), but resulted in a significant increase in the levels of MMP-9 mRNA and protein at 24 and 72 h, respectively (p < 0.01). Increases in MMP-9 mRNA and protein after TBI were proportional to injury severity in this model. The effects of post-traumatic hypothermia on the expression of MMP-9 may partially explain the observed effects of post-traumatic temperature on secondary injury after TBI.
Assuntos
Temperatura Corporal , Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Animais , Western Blotting , Lesões Encefálicas/genética , Masculino , Metaloproteinase 9 da Matriz/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índices de Gravidade do TraumaRESUMO
In this investigation, we evaluated the effect of post-traumatic mild hypothermia on cell death in the hippocampus after fluid percussion traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n = 40/group): TBI with hypothermia treatment (32 degrees C), TBI with normothermia (37 degrees C), and sham injury. The TBI model was induced by a fluid percussion TBI device. Mild hypothermia (32 degrees C) was achieved by partial immersion in a water bath (0 degrees C) under general anesthesia for 4h. All rats were killed at 24 or 72h after TBI. The ipsilateral hippocampal CA1 in all rats were analyzed by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL), and 4',6-diamidino-2-phenylindole (DAPI) staining for determining cell death. Caspase-3 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. At 24h, based on TUNEL and DAPI results, the cell death index was 28.80 +/- 2.60% and 32.10 +/- 1.40% in the normothermia TBI group, while reaching only 14.30 +/- 2.70% and 18.40 +/- 2.10% in the hypothermic TBI group (p < 0.01). Based on RT-PCR and Western blotting results, the expression of caspase-3 was 210.20 +/- 5.30% and 170.30 +/- 4.80% in the normothermic TBI group, while reaching only 165.10 +/- 3.70% and 130.60 +/- 4.10% in the hypothermic TBI group (p < 0.05). At 72h, based on TUNEL and DAPI results, the cell death index was 20.80 +/- 2.50% and 25.50 +/- 1.80% in the normothermic TBI group, while reaching only 10.20 +/- 2.60% and 15.50 +/- 2.10% in the hypothermic TBI group (p < 0.01). Based on RT-PCR and Western blotting results, the expression of caspase-3 was 186.20 +/- 6.20% and 142.30 +/- 5.10% in the normothermic TBI group, versus only 152.10 +/- 3.60% and 120.60 +/- 3.90% in the hypothermic TBI group (p < 0.05). Based on our findings, we conclude that post-traumatic hypothermia significantly attenuates cell death within the hippocampus following fluid percussion injury. Taken together with other studies, these observations support the premise that post-traumatic mild hypothermia can provide cerebral protection for patients with TBI.
Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/terapia , Hipocampo/patologia , Hipotermia Induzida/métodos , Animais , Western Blotting , Temperatura Corporal , Caspase 3/genética , Caspase 3/metabolismo , Morte Celular , Corantes Fluorescentes , Hipocampo/fisiologia , Marcação In Situ das Extremidades Cortadas , Indóis , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
It is well recognized that brain death starts to occur just 4-6 min after cardiac arrest, and few attempts at resuscitation succeed after 10 min of severe cerebral ischemia and anoxia. We sought to determine the therapeutic window of selective cerebral profound hypothermia of primates following severe cerebral ischemia in primates. Fourteen rhesus monkeys with severe cerebral ischemia were divided into four groups: normothermia (n = 3); profound hypothermia I (n = 4), with cooling initiated 10 min after ischemia; profound hypothermia II (n = 4), with cooling initiated 15 min after ischemia; and profound hypothermia III (n = 3), with cooling initiated 20 min after ischemia. Severe cerebral ischemia was induced by clamping both the internal and external carotid arteries, as well as the internal and external jugular veins. Profound cerebral hypothermia (15.8 degrees +/- 0.9 degrees C) was achieved and maintained for 60 min, and the animals were then re-warmed gradually. All four animals in hypothermia group I survived without any neurological deficits. Only 1 animal survived and 3 animals died in hypothermia group II. All 4 animals died in both hypothermia group III and the normothermia group. Neurological functions were normal in all surviving animals, and MRI scans showed no cerebral infarction in these animals. Microscopic examination showed no injured neurons in the hippocampus and cerebral cortex of the surviving animals, and showed that the heart, lung, liver, and kidneys were normal in these animals. Our data indicate that post-ischemic profound cerebral hypothermia provided significant cerebral protection with no systemic complications, and that the effective therapeutic window is more than 10 min, but less than 15 min, after severe cerebral ischemia.
Assuntos
Isquemia Encefálica/terapia , Hipotermia Induzida/métodos , Ressuscitação/métodos , Animais , Isquemia Encefálica/patologia , Macaca mulatta , Imageamento por Ressonância Magnética , Recuperação de Função Fisiológica , TempoRESUMO
To investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. 210 adult male Sprague Dawley rats were randomly assigned to the groups of TBI with hypothermia treatment (32 degrees C), TBI with normothermia (37 degrees C), and sham injured control. TBI model was induced by fluid percussion TBI device. Mild hypothermia (32 degrees C) was achieved by partial immersion in a water bath (0 degrees C) under general anesthesia for 4 hours. All the rats were killed at 4, 6, 12, 24, 48, 72h and 1w after TBI. The mRNA and protein level of TIMP-3 in both injured and uninjured hemispheres of each group were measured using RT-PCR and western blot techniques. In the normothermic group, TIMP-3 levels in both injured and uninjured hemispheres were significantly increased after TBI compared with those of sham injured animals (p < 0.01). In contrast, post-traumatic hypothermia significantly attenuated such an increase. According to the RT-PCR and western blot analysis, the maximum mRNA levels of TIMP-3 were reduced to 60.60%+/-2.30, 55.83%+/-1.80, 66.03%+/-2.10 and 64.51%+/-1.50 of the corresponding values in the normothermic group in injured and uninjured hemispheres (cortex and hippocampus) by hypothermia treatment, respectively (p < 0.01), while the respective maximum protein levels of TIMP-3 were reduced to 57.50%+/-1.50, 52.67%+/-2.20, 60.31%+/-2.50and 54.76%+/-1.40 (p < 0.01). Our data suggests that moderate F-P brain injury would significantly upregulate TIMP-3 expression, while such an increase could be efficiently suppressed by hypothermia treatment.