RESUMO
BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).
Assuntos
Ketamina , Procedimentos Ortopédicos , Complicações Cognitivas Pós-Operatórias , Cuidados Pré-Operatórios , Humanos , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Método Duplo-Cego , Idoso , Masculino , Feminino , Procedimentos Ortopédicos/efeitos adversos , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Transtornos Neurocognitivos/prevenção & controle , Testes Neuropsicológicos , Delírio/prevenção & controleRESUMO
Perioperative neurocognitive disorders (PNDs) are now considered the most common neurological complication in older adult patients undergoing surgical procedures. A significant increase exists in the incidence of post-operative disability and mortality in patients with PNDs. However, no specific treatment is still available for PNDs. Recent studies have shown that exercise may improve cognitive dysfunction-related disorders, including PNDs. Neuroinflammation is a key mechanism underlying exercise-induced neuroprotection in PNDs; others include the regulation of gut microbiota and mitochondrial and synaptic function. Maintaining optimal skeletal muscle mass through preoperative exercise is important to prevent the occurrence of PNDs. This review summarizes current clinical and preclinical evidence and proposes potential molecular mechanisms by which perioperative exercise improves PNDs, providing a new direction for exploring exercise-mediated neuroprotective effects on PNDs. In addition, it intends to provide new strategies for the prevention and treatment of PNDs.
Assuntos
Exercício Físico , Transtornos Neurocognitivos , Assistência Perioperatória , Humanos , Transtornos Neurocognitivos/prevenção & controle , Transtornos Neurocognitivos/etiologia , Animais , Assistência Perioperatória/métodos , Exercício Físico/fisiologia , Período PerioperatórioRESUMO
Perioperative neurocognitive disorder (PND) is a common disorder following anesthesia and surgery, especially in the elderly. The complex cellular and molecular processes are involved in PND, but the underlying pathogenesis of which remains inconclusive due to conflicting data. A growing body of evidence has been shown that perioperative systemic inflammation plays important roles in the development of PND. We reviewed the relevant literature retrieved by a search in the PubMed database (on July 20, 2023). The search terms used were "delirium", "post operative cognitive dysfunction", "perioperative neurocognitive disorder", "inflammation" and "systemic", alone and in combination. All articles identified were English-language, full-text papers. The ones cited in the review are those that make a substantial contribution to the knowledge about systemic inflammation and PNDs. The aim of this review is to bring together the latest evidence for the understanding of how perioperative systemic inflammation mediates neuroinflammation and brain injury, how the inflammation is regulated and how we can translate these findings into prevention and/or treatment for PND.
Assuntos
Transtornos Neurocognitivos , Doenças Neuroinflamatórias , Humanos , Idoso , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/patologia , Transtornos Neurocognitivos/prevenção & controle , Inflamação/prevenção & controleRESUMO
Perioperative neurocognitive disorders are a group of conditions characterised by changes in cognitive function, which affect older people after surgery and anaesthesia. Multicomponent interventions may reduce the impact of perioperative neurocognitive disorders on patients and healthcare systems.
Assuntos
Anestesia , Anestesiologia , Humanos , Idoso , Anestesia/efeitos adversos , Cognição , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controleRESUMO
The dysfunction of the blood-brain barrier could contribute to the pathogenesis of the perioperative neurocognitive disorder. In a recent study published in the British Journal of Anaesthesia, Yang and colleagues developed an innovative microï¬uidics-assisted blood-brain barrier device to investigate the effects of neuroimmune interactions on blood-brain barrier opening. The findings are important and timely to understanding the mechanistic insights of perioperative neurocognitive disorder.
Assuntos
Barreira Hematoencefálica , Microfluídica , Humanos , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controleRESUMO
Perioperative neurocognitive disorders (PND) is a common postoperative complication associated with regional or general anesthesia and surgery. Growing evidence in both patient and animal models of PND suggested that neuroinflammation plays a critical role in the development and progression of this problem, therefore, mounting efforts have been made to develop novel therapeutic approaches for PND by targeting specific factors or steps alongside the neuroinflammation. Multiple studies have shown that perioperative anti-neuroinflammatory strategies via administering pharmacologic agents or performing nonpharmacologic approaches exert benefits in the prevention and management of PND, although more clinical evidence is urgently needed to testify or confirm these results. Furthermore, long-term effects and outcomes with respect to cognitive functions and side effects are needed to be observed. In this review, we discuss recent preclinical and clinical studies published within a decade as potential preventive and therapeutic approaches targeting neuroinflammation for PND.
Assuntos
Cognição , Transtornos Neurocognitivos , Animais , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Anestesia Geral/efeitos adversosRESUMO
Postoperative neurocognitive disorders are common neurological complications following surgery that are generally characterized by varying degrees of cognitive impairment. Postoperative neurocognitive disorders can exhibit as short-term postoperative delirium and/or long-term postoperative cognitive dysfunction. In addition, postoperative neurocognitive disorders may result in poor outcomes in patients, and are a leading cause of postoperative morbidity and mortality, particularly in elderly patients. Recently, there has been a heightened interest in mechanisms and clinical treatments for postoperative neurocognitive disorders. Though some influencing factors and mechanisms of postoperative neurocognitive disorders have been revealed, they remain troublesome problems in clinical departments. Dexmedetomidine is a commonly used anesthetic adjuvant that may help improve postoperative cognitive impairment, especially the conditions of a postoperative acute event (postoperative delirium, within 1 week after operation) and delayed neurocognitive recovery (postoperative cognitive dysfunction, up to 30 days). In the recent literature, dexmedetomidine has been shown to exert positive effects on cognitive impairment in clinical and animal studies, especially for postoperative neurocognitive disorders. However, not all clinical findings support this efficacy. Though some mechanisms of dexmedetomidine on postoperative neurocognitive disorders have been proposed, such as signaling pathways associated with inflammation and apoptosis, this evidence is fragmentary and disputed in the literature. Therefore, this article aims to review the potential biological mechanisms underlying dexmedetomidine's effects on postoperative neurocognitive disorders, providing a reference for future studies.
Assuntos
Dexmedetomidina , Transtornos Neurocognitivos , Complicações Cognitivas Pós-Operatórias , Adjuvantes Anestésicos/uso terapêutico , Delírio/prevenção & controle , Dexmedetomidina/uso terapêutico , Transtornos Neurocognitivos/prevenção & controle , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Humanos , IdosoRESUMO
PURPOSE OF REVIEW: Reducing the risk of HIV-associated neurocognitive disorders (HAND) is an elusive treatment goal for people living with HIV. Combination antiretroviral therapy (cART) has reduced the prevalence of HIV-associated dementia, but milder, disabling HAND is an unmet challenge. As newer cART regimens that more consistently suppress central nervous system (CNS) HIV replication are developed, the testing of adjunctive neuroprotective therapies must accelerate. RECENT FINDINGS: Successes in modifying cART regimens for CNS efficacy (penetrance, chemokine receptor targeting) and delivery (nanoformulations) in pilot studies suggest that improving cART neuroprotection and reducing HAND risk is achievable. Additionally, drugs currently used in neuroinflammatory, neuropsychiatric, and metabolic disorders show promise as adjuncts to cART, likely by broadly targeting neuroinflammation, oxidative stress, aerobic metabolism, and/or neurotransmitter metabolism. Adjunctive cognitive brain therapy and aerobic exercise may provide additional efficacy. Adjunctive neuroprotective therapies, including available FDA-approved drugs, cognitive therapy, and aerobic exercise combined with improved cART offer plausible strategies for optimizing the prevention and treatment of HAND.
Assuntos
Complexo AIDS Demência , Infecções por HIV , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controle , Neuroproteção , Neurotransmissores/uso terapêutico , Receptores de Quimiocinas/uso terapêuticoRESUMO
Perioperative neurocognitive disorders (NCDs) refer to neurocognitive abnormalities detected during the perioperative periods, including preexisting cognitive impairment, preoperative delirium, delirium occurring up to 7 days after surgery, delayed neurocognitive recovery, and postoperative NCD. The Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) is the golden standard for diagnosing perioperative NCDs. Given the impracticality of using the DSM-5 by non-psychiatric practitioners, many diagnostic tools have been developed and validated for different clinical scenarios. The etiology of perioperative NCDs is multifactorial and includes predisposing and precipitating factors. Identifying these risk factors is conducive to preoperative risk stratification and perioperative risk reduction. Prevention for perioperative NCDs should include avoiding possible contributors and implementing nonpharmacologic and pharmacological interventions. The former generally includes avoiding benzodiazepines, anticholinergics, prolonged liquid fasting, deep anesthesia, cerebral oxygen desaturation, and intraoperative hypothermia. Nonpharmacologic measures include preoperative cognitive prehabilitation, comprehensive geriatric assessment, implementing fast-track surgery, combined use of regional block, and sleep promotion. Pharmacological measures including dexmedetomidine, nonsteroidal anti-inflammatory drugs, and acetaminophen are found to have beneficial effects. Nonpharmacological treatments are the first-line measures for established perioperative NCDs. Pharmacological treatments are still limited to severely agitated or distressed patients.
Assuntos
Anestesia , Disfunção Cognitiva , Delírio , Idoso , Anestesia/efeitos adversos , Disfunção Cognitiva/etiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: Postoperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulate, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice undergoing abdominal surgery. Further, we examined the underlying mechanisms from the perspective of neuroinflammatory state and synaptic plasticity in the hippocampus. METHODS: 18-month-old C57BL/6N mice were trained for 5 weeks using a ladder-climbing protocol with progressively increasing weight loading. Preoperative baseline body parameters, cognitive performance and neuroinflammatory states were assessed and compared between sedentary and trained groups of 9-month-old and 18-month-old mice. To access the neuroprotective effect of resistance training on postoperative aged mice, both sedentary and trained mice were subjected to a laparotomy under 3% sevoflurane anesthesia. Cognitive performance on postoperative day 14, hippocampal neuroinflammation, mitochondrial dysfunction and synaptic plasticity were examined and compared during groups. RESULTS: 18-month-old mice have increased body weight, higher peripheral and central inflammatory status, reduction in muscle strength and cognitive performance compared with middle-aged 9-month-old mice, which were improved by resistance exercise. In the laparotomy group, prehabilitative resistant exercise improved cognitive performance and synaptic plasticity, reduced inflammatory factors and glial cells activation after surgery. Furthermore, resistance exercise activated hippocampal PGC-1α/BDNF/Akt/GSK-3ß signaling and improved mitochondrial biogenesis, as well as ameliorated mitochondrial dynamics in postoperative-aged mice. CONCLUSIONS: Resistance exercise reduced risk factors for perioperative neurocognitive disorders such as increased body weight, elevated inflammatory markers, and pre-existing cognitive impairment. Accordantly, preoperative resistance exercise improved surgery-induced adverse effects including cognitive impairment, synaptic deficit and neuroinflammation, possibly by facilitate mitochondrial health through the PGC1-a/BDNF pathway.
Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Treinamento Resistido , Idoso , Animais , Peso Corporal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controle , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Treinamento Resistido/métodosRESUMO
BACKGROUND: To investigate whether short-term perioperative cognitive therapy combined with rehabilitation exercise decreases the incidence of neurocognitive disorder (NCD) in elderly patients who have undergone hip joint replacement surgery. This was a randomized, parallel controlled trial on elderly patients who underwent unilateral total hip joint replacement surgery at the Third Xiangya Hospital of Central South University. METHODS: Patients in the perioperative cognitive therapy combined with rehabilitation exercise group underwent preoperative cognitive training and postoperative cognitive training, rehabilitation exercise, and standardized health care services; the control group received only postoperative standardized health care service. Patients with NCD were defined as those with two or more abnormalities on 11 neuropsychological tests. Of the 607 individuals that we screened, 86 (exercise, 50; control, 36) who completed the study were included. RESULTS: The baseline characteristics were similar for the two groups. The incidence of NCD in the exercise group (10%, 5/50) was significantly lower than that in the control group (27.8%, 10/36) (P=0.032). The HVLT-R, HVLT-R delayed recall test, and HVLT-R recognition discriminating index were significantly improved in the exercise group compared with the control group (all P<0.05). Our findings highlight the clinical significance of perioperative cognitive exercise combined with rehabilitation exercise in preventing NCD among patients after surgery and anesthesia. CONCLUSIONS: Our study indicates that perioperative cognitive therapy combined with rehabilitation exercise can effectively reduce the incidence of NCD in elderly patients after total hip joint replacement surgery.
Assuntos
Artroplastia de Quadril , Terapia Cognitivo-Comportamental , Idoso , Terapia por Exercício , Humanos , Incidência , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/prevenção & controleRESUMO
Perioperative neurological disorders are important causes of postoperative disability and even perioperative death, bringing a huge challenge to the vulnerable and increasing aging population. Perioperative neurological disorders usually contain ischemic stroke, hemorrhagic stroke, and neurocognitive disorders during the perioperative period. Although a few prevention and treatment strategies have been developed for each disorder, there is still a lack of effective treatments and the underlying mechanisms are far from well-understood. This special issue is dedicated to introducing the recent advances in new strategies towards the management of perioperative neurological disorders. The issue collects research articles and reviews focusing on the neuroprotection mechanisms and application of novel technologies in perioperative neurological disorders, including machine learning and nano-delivery system. These works help to shed lights on developing novel therapeutic targets of perioperative neurological disorders in the pursuit of better recovery and prognosis of the surgical patients.
Assuntos
AVC Isquêmico , Doenças do Sistema Nervoso , Idoso , Humanos , Doenças do Sistema Nervoso/terapia , Transtornos Neurocognitivos/prevenção & controle , Neuroproteção , Período PerioperatórioRESUMO
Peri-operative neurocognitive disorders are the most common complication experienced by older individuals undergoing anaesthesia and surgery. Peri-operative neurocognitive disorders, particularly postoperative delirium, result in long-term poor outcomes including: death; dementia; loss of independence; and poor cognitive and functional outcomes. Recent changes to the nomenclature of these disorders aims to align peri-operative neurocognitive disorders with cognitive disorders in the community, with consistent definitions and clinical diagnosis. Possible mechanisms include: undiagnosed neurodegenerative disease; inflammation and resulting neuroinflammation; neuronal damage; and comorbid systemic disease. Pre-operative frailty represents a significant risk for poor postoperative outcomes; it is associated with an increase in the incidence of cognitive decline at 3 and 12 months postoperatively. In addition to cognitive decline, frailty is associated with poor functional outcomes following elective non-cardiac surgery. It was recently shown that 29% of frail patients died or experienced institutionalisation or new disability within 90 days of major elective surgery. Identification of vulnerable patients before undergoing surgery and anaesthesia is the key to preventing peri-operative neurocognitive disorders. Current approaches include: pre-operative delirium and cognitive screening; blood biomarker analysis; intra-operative management that may reduce the incidence of postoperative delirium such as lighter anaesthesia using processed electroencephalography devices; and introduction of guidelines which may reduce or prevent delirium and postoperative neurocognitive disorders. This review will address these issues and advocate for an approach to care for older peri-operative patients which starts in the community and continues throughout the pre-operative, intra-operative, postoperative and post-discharge phases of care management, involving multidisciplinary medical teams, as well as family and caregivers wherever possible.
Assuntos
Idoso Fragilizado , Transtornos Neurocognitivos/prevenção & controle , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Idoso Fragilizado/psicologia , Humanos , Mediadores da Inflamação/metabolismo , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/psicologia , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/psicologiaRESUMO
BACKGROUND: Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2. METHODS: Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively. RESULTS: Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits. CONCLUSIONS: MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.
Assuntos
Envelhecimento/metabolismo , Antígeno 96 de Linfócito/biossíntese , Transtornos Neurocognitivos/metabolismo , Complicações Pós-Operatórias/metabolismo , Receptores de GABA-A/biossíntese , Envelhecimento/efeitos dos fármacos , Animais , Células Cultivadas , Feminino , Agonistas GABAérgicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Período Perioperatório/efeitos adversos , Período Perioperatório/tendências , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , GravidezRESUMO
BACKGROUND: Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring. METHODS AND FINDINGS: Between April 2014 and April 2015, we followed 421 Malawian mother-baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur-Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], -7.53 [-13.04, -2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], -8.57 [-13.09, -4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies. CONCLUSIONS: This mother-baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.
Assuntos
Transtornos do Desenvolvimento da Linguagem/etiologia , Malária/fisiopatologia , Transtornos Neurocognitivos/etiologia , Complicações Infecciosas na Gravidez , Estudos de Coortes , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Malária/embriologia , Malária/imunologia , Malaui , Masculino , Transtornos Neurocognitivos/prevenção & controle , Testes Neuropsicológicos , Gravidez , Complicações Infecciosas na Gravidez/imunologiaRESUMO
Perioperative neurocognitive disorder (PND) is the mild cognitive impairment associated with surgery and anesthesia. It is a common surgical complication in the elderly. An important mechanism of PND is the surgically induced neuroinflammation. The interaction between the neuronal surface protein CD200 and its receptor in microglia, CD200R1, is an important regulatory pathway to control neuroinflammation. However, the potential role of the CD200-CD200R1 pathway in the acute period of PND has not been fully investigated. In this study, in a PND mouse model, we first measured the protein expression level of CD200, CD200R1, and the related pro- and anti-inflammatory cytokines in the hippocampus. Then, we investigated cognitive function, neuroinflammation and postsynaptic density protein 95 (PSD-95) expression after the injection of CD200-Fc (agonist), CD200R1-Fc (antagonist) or IgG1-Fc (vehicle) into lateral ventricle in PND models. Compared with the control group, the expression of CD200 was up-regulated at day 1 after surgery in PND models. The injection of the CD200-Fc into the lateral ventricle could mitigate primed neuroinflammation and cognitive decline, increase the expression of PSD-95 at day 1 after surgery in PND models. In conclusion, we have demonstrated that CD200-CD200R1 signaling was involved in the acute inflammatory process of PND, and activating CD200R1 can inhibit neuroinflammation and attenuate PND. Thus, the CD200-CD200R1 axis is a potential novel target for PND prevention and treatment.
Assuntos
Antígenos CD/metabolismo , Fígado/cirurgia , Transtornos Neurocognitivos/prevenção & controle , Doenças Neuroinflamatórias/prevenção & controle , Receptores de Orexina/metabolismo , Assistência Perioperatória , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Animais , Antígenos CD/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/patologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Receptores de Orexina/genéticaRESUMO
Whole-brain radiotherapy (WBRT) is the mainstay of therapy in treating cancer patients with brain metastases, but unfortunately, it might also lead to decline in neurocognitive function. This study aims to investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Retrospectively, 47 patients diagnosed with brain metastases of non-small cell lung cancer (NSCLC) between 2015-01-01 and 2017-12-31 at the Department of Oncology, XXX Hospital were selected and divided into 2 groups. Group A (n = 27) received HA-WBRT, whereas group B (n = 20) received WBRT. Neurocognitive function was analyzed at baseline and at 3, 6, 9, 12 and 24 months after radiotherapy, using Mine-Mental State Examination (MMSE) scales and Montreal Cognitive Assessment (MoCA) scales. The OS, PFS and tumor recurrence sites were also analyzed. When evaluated at 12 and 24 months after radiotherapy, the cognitive function scores of the hippocampal avoidance group were significantly higher than those of the non-hippocampal avoidance group (P < 0.001). In terms of patient survival, there was no significant difference in OS (P = 0.2) and PFS (P = 0.18) between these 2 groups. Fourteen patients in group A and 12 patients in group B had brain tumor recurrence after radiation, only one patient in group A occurred within 5 mm from the edge of the hippocampus (P > 0.05). In conclusion, HA-WBRT might have a protective effect on long-term neurocognitive function and did not affect patient survival.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Irradiação Craniana/métodos , Hipocampo/efeitos da radiação , Neoplasias Pulmonares/radioterapia , Transtornos Neurocognitivos/prevenção & controle , Tratamentos com Preservação do Órgão/métodos , Lesões por Radiação/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/patologia , Prognóstico , Lesões por Radiação/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos RetrospectivosRESUMO
Neurocognitive impairment is common in sickle cell disease (SCD) and is associated with significant functional limitations. In a cross-sectional analysis, we examined the association between hydroxyurea (HU) treatment and neurocognitive functioning from school-age to young adulthood in individuals with SCD. A total of 215 patients with HbSS/HbSß0 -thalassaemia (71% HU treated) and 149 patients with HbSC/HbSß+ -thalassaemia (20% HU treated) completed neurocognitive measures at one of four developmental stages: school-age (age 8-9 years), early adolescence (age 12-13 years), late adolescence (age 16-17 years) and young adulthood (ages 19-24 years). For participants with multiple assessments, only the most recent evaluation was included. In multivariable analysis adjusted for social vulnerability, HU treatment and sex, older age was associated with a reduction in overall intelligence quotient (IQ) of 0·55 points per year of life [standard error (SE) = 0·18, false discovery rate adjusted P value (PFDR) = 0.01] for patients with HbSS/HbSß0 -thalassaemia. Earlier initiation of HU (n = 152) in HbSS/HbSß0 -thalassaemia was associated with higher scores on neurocognitive measures across most domains, including IQ [estimate (SE) 0·77 (0·25)/year, PFDR = 0·01], after adjusting for social vulnerability, sex and treatment duration. These results support the early use of HU to limit the detrimental neurocognitive effects of SCD, while highlighting the need for additional measures to further mitigate neurocognitive deterioration.