Dataset Information

Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

ABSTRACT: Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limited attempts have been made to study this cognitive domain in preclinical models. Here we implemented the 5-choice serial reaction time task (5-CSRTT) to evaluate attention in a clinically relevant mouse model following orthopedic surgery. The 5-CSRTT showed a time-dependent impairment in the number of responses made by the mice acutely after orthopedic surgery, with maximum impairment at 24 h and returning to pre-surgical performance by day 5. Similarly, the latency to the response was also delayed during this time period but returned to pre-surgical levels within several days. While correct responses decreased following surgery, the accuracy of the response (e.g., selection of the correct nose-poke) remained relatively unchanged. In a separate cohort we evaluated neuroinflammation and blood-brain barrier (BBB) dysfunction using clarified brain tissue with light-sheet microscopy. CLARITY revealed significant changes in microglial morphology and impaired astrocytic-tight junction interactions using high-resolution 3D reconstructions of the neurovascular unit. Deposition of IgG, fibrinogen, and autophagy markers (TFEB and LAMP1) were also altered in the hippocampus 24 h after surgery. Together, these results provide translational evidence for the role of peripheral surgery contributing to delirium-like behavior and disrupted neuroimmunity in adult mice.

SUBMITTER: Velagapudi R

PROVIDER: S-EPMC6918861 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

Velagapudi Ravikanth R Subramaniyan Saraswathi S Xiong Chao C Porkka Fiona F Rodriguiz Ramona M RM Wetsel William C WC Terrando Niccolò N

Frontiers in immunology 20191119

Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limited attempts have been made to study this cognitive domain in preclinical models. Here we implemented the 5-choice serial reaction time task (5-CSRTT) to evaluate attention in a clinically relevant mouse model following orthopedic surgery. The 5 ...[more]

PMID: 31911786

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Project description:BackgroundPostoperative delirium (POD) is common and has negative effects on elderly patients. There is a critical need to identify patients at high risk of POD so that providers can better offer targeted interventions in the preoperative and intraoperative periods. We aimed to characterize the prevalence of preoperative anxiety and investigate whether preoperative anxiety predicted the onset of POD in elderly patients undergoing elective orthopedic surgery.MethodsWe conducted a prospective observational cohort study of elderly patients (aged 65 years or older) undergoing elective orthopedic surgery. Preoperative anxiety was assessed using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), with clinically significant values defined as HADS-A>7. POD was diagnosed according to the Confusion Assessment Method (CAM) criteria on the 5 postoperative days. To determine the independent risk factors for POD, multivariable logistic regression was conducted, including those variables with a p-value <0.05 at univariate analysis.ResultsThere were 263 patients included in the study. Seventy-three (27.8%) patients were diagnosed to be POD. Median duration of delirium was 2 days. Forty (15.2%) patients were assessed to experience preoperative anxiety. The occurrence of preoperative anxiety in total hip arthroplasty (THA), proximal femoral nail antirotation (PFNA), and total knee arthroplasty (TKA) was 12.5%, 16.1%, and 19.5%, respectively. Based on multivariable analysis, only age (odds ratio [OR]= 1.099, 95% Confidence Interval [CI]: 1.013-1.192; P=0.023), Mini Mental State Examination (MMSE) (OR= 0.603, 95% CI: 0.432-0.842; P=0.003) and preoperative anxiety (OR= 3.119, 95% CI: 1.144-8.500; P=0.026) were independently associated with POD.ConclusionIn conclusion, the current study reveals that preoperative anxiety helps to predict the risk of POD in elderly patients undergoing elective orthopedic surgery. Relieving preoperative anxiety could be a new target for preventive interventions to reduce POD.

Project description:BackgroundPostoperative delirium (POD) is a common complication after orthopedic surgery in elderly patients. The elderly may experience drastic changes in autonomic nervous system (ANS) activity and circadian rhythm disorders after surgery. Therefore, we intend to explore the relationship between postoperative long-term heart rate (HR) variability (HRV), as a measure of ANS activity and circadian rhythm, and occurrence of POD in elderly patients.MethodsThe study population of this cohort was elderly patients over 60 years of age who scheduled for orthopedic surgery under spinal anesthesia. Patients were screened for inclusion and exclusion criteria before surgery. Then, participants were invited to wear a Holter monitor on the first postoperative day to collect 24-h electrocardiographic (ECG) data. Parameters in the time domain [the standard deviation of the normal-to-normal (NN) intervals (SDNN), mean of the standard deviations of all the NN intervals for each 5-min segment of a 24-h HRV recording (SDNNI), and the root mean square of successive differences of the NN intervals (RMSSD)] and frequency domain [heart rate (HR), high frequency (HF), low frequency (LF), very low frequency (VLF), ultra low frequency (ULF), and total power (TP)] were calculated. Assessment of delirium was performed daily up to the seventh postoperative day using the Chinese version of the 3-Min Diagnostic Interview for CAM-defined Delirium (3D-CAM). The relationship between HRV and POD, as well as the association between HRV and duration of POD, was assessed.ResultsOf the 294 cases that finally completed the follow-up, 60 cases developed POD. Among the HRV parameters, SDNNI, VLF, and ULF were related to the occurrence of POD. After adjustment for potential confounders, the correlation between HRV indices and POD disappeared. Through stratified analysis, two significant negative correlations emerged: ULF in young-old participants and SDNNI, VLF, and ULF in male patients.ConclusionThe lower HRV parameters may be related to the occurrence of POD, and this correlation is more significant in young-old and male patients. ANS disorders and rhythm abnormalities reflected by HRV changes may represent a possible mechanism that promotes POD.

Dataset Information

Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

Publications

Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

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