scholarly journals Dietary Choline Protects Against Cognitive Decline After Surgery in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Sara V. Maurer ◽  
Cuicui Kong ◽  
Niccolò Terrando ◽  
Christina L. Williams
Keyword(s):  
Cognitive Deficits ◽  
Tibial Fracture ◽  
Dietary Intervention ◽  
Granule Cells ◽  
Subgranular Zone ◽  
Common Complication ◽  
Impaired Memory ◽  
Post Surgery ◽  
Dietary Choline ◽  
Fracture Surgery

Perioperative neurocognitive disorders (PNDs) are a common complication following procedures such as orthopedic surgery. Using a mouse model of tibial fracture and repair surgery, we have previously shown an increase in neuroinflammation and hippocampal-dependent cognitive deficits. These changes were ameliorated with the addition of a cholinergic agonist. Here, we sought to examine the effects of a high-choline diet for 3 weeks prior to tibial fracture surgery. We evaluated memory using novel object recognition (NOR) as well as young neurons and glial cell morphology at 1 day and 2 weeks post-surgery. At both time points, tibial fracture impaired NOR performance, and dietary choline rescued these impairments. Astrocytic density and hilar granule cells increased 1 day after tibial fracture, and these increases were partially blunted by dietary choline. An increase in young neurons in the subgranular zone of the dentate gyrus was found 2 weeks after tibial fracture. This increase was partially blunted by choline supplementation. This suggests that shortly after tibial fracture, hippocampal reorganization is a possible mechanism for acute impaired memory. These findings together suggest that non-pharmaceutical approaches, such as pre-surgical dietary intervention with choline, may be able to prevent PNDs.

Increasing dietary choline attenuates spatial memory deficits resulting from exposure to the chemotherapeutic agents cyclophosphamide and doxorubicin

2021 ◽  
pp. 026988112110297
Author(s):  
Bethany E Johns ◽  
Melissa Ficken ◽  
Melanie E Engberg ◽  
Lynn Wecker ◽  
Rex M Philpot
Keyword(s):  
Spatial Memory ◽  
Cognitive Deficits ◽  
Memory Deficits ◽  
Chemotherapeutic Agents ◽  
Standard Diet ◽  
Cognitive Domains ◽  
Intravenous Injections ◽  
Impaired Memory ◽  
Dietary Choline

Background: Choline supplementation (+Ch) improves cognitive function in impaired animals and humans. Chemotherapy-related cognitive deficits (CRCDs) occur in cancer patients, and these deficits persist following treatment, adversely impacting quality of life. To date, there are no approved treatments for this condition. Aim: Because +Ch improves impaired memory, it was of interest to determine whether +Ch can attenuate spatial memory deficits induced by the chemotherapeutic agents doxorubicin (DOX) and cyclophosphamide (CYP). Methods: Female BALB/C mice, 64 days of age, were trained in the Morris water maze and baseline performance determined on day 15. Following baseline assessment, mice were placed on +Ch diet (2.0% Ch) or remained on standard diet (0.12% Ch). Mice received intravenous injections of DOX (2.5 mg/kg) and CYP (25 mg/kg), or equivalent volumes of saline (0.9% NaCl), on days 16, 23, 30, and 37, and spatial memory was assessed weekly from day 22 to 71. Results: DOX and CYP produced a prolonged impairment in spatial memory as indicated by an increased latency to the correct zone ( p < 0.05), and a decrease in time in the correct zone ( p < 0.05), % of total swim distance in the correct zone ( p < 0.05) and % entries to the correct zone ( p < 0.05). These effects were attenuated by +Ch. Conclusion: Although it remains to be determined whether this effect extends to other cognitive domains and whether +Ch is prophylactic or therapeutic, these findings suggest that +Ch may be an effective intervention for CRCDs.

scholarly journals Identification of hypercoagulability with thrombelastography in patients with hip fracture receiving thromboprophylaxis

2021 ◽  
Vol 64 (3) ◽  
pp. E324-E329
Author(s):  
Daniel You ◽  
Leslie Skeith ◽  
Robert Korley ◽  
Paul Cantle ◽  
Adrienne Lee ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Point Of Care ◽  
Common Complication ◽  
Maximal Amplitude ◽  
Clot Strength ◽  
Hip Fracture Surgery ◽  
Point Of Care Test ◽  
Trochanteric Region ◽  
Fracture Surgery ◽  
Over Time

Background: Venous thromboembolism (VTE) is the second most common complication after hip fracture surgery. We used thrombelastography (TEG), a whole-blood, point-of-care test that can provide an overview of the clotting process, to determine the duration of hypercoagulability after hip fracture surgery. Methods: In this prospective study, consecutive patients aged 51 years or more with hip fractures (trochanteric region or neck) amenable to surgical treatment who presented to the emergency department were eligible for enrolment. Thrombelastography, including calculation of the coagulation index (CI) (combination of 4 TEG parameters for an overall assessment of coagulation) was performed daily from admission until 5 days postoperatively, and at 2 and 6 weeks postoperatively. All patients received 28 days of thromboprophylaxis. We used single-sample t tests to compare mean maximal amplitude (MA) values (a measure of clot strength) to the hypercoagulable threshold of greater than 65 mm, a predictor of in-hospital VTE. Results: Of the 35 patients enrolled, 11 (31%) were hypercoagulable on admission based on an MA value greater than 65 mm, and 29 (83%) were hypercoagulable based on a CI value greater than 3.0; the corresponding values at 6 weeks were 23 (66%) and 34 (97%). All patients had an MA value greater than 65 mm at 2 weeks. Patients demonstrated normal coagulation on admission (mean MA value 62.2 mm [standard deviation (SD) 6.3 mm], p = 0.01) but became significantly hypercoagulable at 2 weeks (mean 71.6 mm [SD 2.6 mm], p < 0.001). There was a trend toward persistent hypercoagulability at 6 weeks (mean MA value 66.2 mm [SD 3.8 mm], p = 0.06). Conclusion: More than 50% of patients remained hypercoagulable 6 weeks after fracture despite thromboprophylaxis. Thrombelastography MA thresholds or a change in MA over time may help predict VTE risk; however, further study is needed.

scholarly journals The Repair of a Distal (one – third) Tibial Fracture in a Local Cock (Gallus gallus domesticus)

2018 ◽  
Vol 1 (1) ◽  
pp. 65-73
Author(s):  
R. O. S Okafor
Keyword(s):  
Tibial Fracture ◽  
Gallus Gallus ◽  
Fracture Repair ◽  
Gallus Domesticus ◽  
Radiographic Examination ◽  
Gallus Gallus Domesticus ◽  
Post Surgery ◽  
Intramedullary Pinning ◽  
Post Operation ◽  
The Right

A local cock(Gallus gallus domesticus) weighing 1.2 kg and kept as a pet was referred to the Veterinary Teaching Hospital (VTH), University of Abuja (UA) with the chief complaint of right limb lameness for three days. A close observation showed that the limb was dangling and had a fresh cut on the skin at the distal 1/3 of the tibia. The region was swollen and had a light-greenish colour suspected to be a sign of gangrene formation. Radiographic examination of the region confirmed a complete oblique simple fracture of the distal 1/3 of the tibia of the right limb. The cause of the fracture was unknown. Under Xylazine hydrochloride and Ketamine hydrochloride anaesthesia, the fracture was repaired through an open reduction with intramedullary pin. Eleven days post-surgery, the cock was found to bear slight weight on the limb. Clinical examination three weeks post operation showed normal usage of the limb and radiological evidence of good fracture healing. The intramedullary pinning appeared to be effective for the management of this simple tibial fracture in the local cock. This report appears to be the first intensive fracture repair documented in the local cock..

scholarly journals Longitudinal Connectome Analyses following Low-Grade Glioma Neurosurgery: Implications for Cognitive Rehabilitation

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv8-iv8
Author(s):  
Anujan Poologaindran ◽  
Mike Hart ◽  
Tom Santarius ◽  
Stephen Price ◽  
Rohit Sinha ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Cognitive Rehabilitation ◽  
Fluid Intelligence ◽  
Higher Order ◽  
Optimal Time ◽  
Single Subject ◽  
Low Grade ◽  
Post Surgery ◽  
Cognitive Data

Abstract Aims Low-grade gliomas (LGG) slowly grow and infiltrate the brain's network architecture (the connectome). Unlike strokes that acutely damage the connectome, LGGs intricately remodel it, leading to varying deficits in executive function (i.e. attention, concentration, working memory). By longitudinally mapping the “mesoscale” architecture of the connectome, we may begin to systematically accelerate domain-general cognitive rehabilitation in LGG patients. In this study, we pursued the following aims: 1) track cognitive and connectome trajectories following LGG surgery, 2) determine optimal time period for cognitive rehabilitation, and 3) distinguish patients with perioperative predictors of long-term cognitive deficits (&gt;1 year). Method With MRI and cognitive data from n=629 individuals across the lifespan, we first validated the structural, functional, and topological relevance of the multiple demand (MD) system for higher-order cognition. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectome and cognitive data: pre-surgery, post-surgery Day 1, Month 3, & 12. We assessed how glioma infiltration, surgery, and rehabilitation affected MD system trajectories at the single-subject level. Deploying transcriptomic and graph theoretical analyses, we tested if perioperative connectome modularity can accurately distinguish long-term cognitive trajectories. Results Controlling for age and sex, the MD system’s multi-scale architecture in health was positively associated with higher-order cognition (Catell’s fluid intelligence). Pre-operative glioma infiltration into the MD system was negatively associated with the number of long-term cognitive deficits (OCS-Bridge cognitive battery), suggesting its functional reorganisation. Mixed-effects modelling demonstrated the resilience of the MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed perioperative modularity can distinguish patients with long-term cognitive deficits at one-year follow-up. Transcriptomic analyses of inter-module connector hubs revealed increased gene expression for mitochondrial metabolism and synaptic plasticity. Conclusion This is the first serial functional mapping of LGG patient trajectories for domain-general cognition. By assessing the mesoscale architecture, we demonstrate how connectomics can help overcome the intrinsic heterogeneity in LGG patients and predict long-term rehabilitation trajectories. We discuss how to identify neurobiologically-grounded personalised targets for 'interventional neurorehabilitation' following LGG surgery.

Neural transplantation and recovery of cognitive function

1995 ◽  
Vol 18 (1) ◽  
pp. 10-35 ◽  
Author(s):  
John D. Sinden ◽  
Helen Hodges ◽  
Jeffrey A. Gray
Keyword(s):  
Cognitive Function ◽  
Cognitive Deficits ◽  
Granule Cells ◽  
Hippocampal Formation ◽  
Fetal Brain ◽  
Pyramidal Cells ◽  
Local Injection ◽  
Projection System ◽  
Ca1 Pyramidal Cells ◽  
Neural Transplants

AbstractCognitive deficits were produced in rats by different methods of damaging the brain: chronic ingestion of alcohol, causing widespread damage to diffuse cholinergic and aminergic projection systems; lesions (by local injection of the excitotoxins, ibotenate, quisqualate, and AMPA) of the nuclei of origin of the forebrain cholinergic projection system (FCPS), which innervates the neocortex and hippocampal formation; transient cerebral ischaemia, producing focal damage especially in the CA1 pyramidal cells of the dorsal hippocampus; and lesions (by local injection of the neurotoxin, colchicine) of the granule cells of the dentate gyrus. Following chronic alcohol or lesions of the FCPS, transplants of cholinergically rich fetal brain tissue into the terminal areas (neocortex and/or hippocampus) restored performance almost to control levels, with a time course consistent with growth of the transplants and integration with host tissue; transplants of cholinergically poor fetal tissue (hippocampus) were without effect, as were transplants of cholinergically rich tissue into the region containing the nuclei of origin of the FCPS. Grafts of primary cells enriched in glia and cultured neuroblastoma cells into the terminal areas of the FCPS were equally effective, suggesting that there are multiple mechanisms by which neural transplants can restore cognitive function following diffuse cholinergic damage. In contrast, after ischaemia- or neurotoxin-induced damage to CA1 or dentate granule cells respectively, cholinergically rich fetal transplants into the damaged hippocampal formation were ineffective in restoring performance. After ischaemic damage, however, performance was restored by suspension grafts of CA1 cells but not by transplants containing CA3 pyramidal cells or granule cells; and after colchicine damage it was restored by solid grafts containing granule but not CA1 pyramidal cells. Furthermore, electrophysiological evidence has demonstrated functional, graft type-specific host-graft functional neuronal connectivity. Thus, restoration of cognitive function by neural transplants is possible after damage to either diffuse (cholinergic) or point-to-point (intrahippocampal) forebrain systems, but the transplant must be appropriate to the damage to be repaired. Because the different types of brain damage studied provide analogues of human alcoholic dementia, Alzheimer's disease, and heart attack, these results are encouraging with regard to the eventual application of neural transplant surgery to the treatment of cognitive deficits in humans.

Association between Intravenous Iron Therapy and Short-term Mortality Risk in Older Patients Undergoing Hip Fracture Surgery: An Observational Study

2021 ◽  
Author(s):  
Silas Zacharias Clemmensen ◽  
Kristian Hay Kragholm ◽  
Dorte Melgaard ◽  
Lene Torp Hansen ◽  
Johannes Riis Jensen ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Intravenous Iron ◽  
Iron Therapy ◽  
Short Term ◽  
Treatment Groups ◽  
Hip Fracture Surgery ◽  
Post Surgery ◽  
Short Term Mortality ◽  
Intravenous Iron Therapy ◽  
Fracture Surgery

Abstract Background: Anemia is common among ortho-geriatric hip fracture patients and is associated with prolonged recovery and increased postoperative mortality rate. Intravenous iron seems to increase hemoglobin recovery and reduce the mortality rate in patients undergoing orthopedic surgeries. This study investigated the association between short-term mortality risk and intravenous iron therapy in older patients undergoing hip fracture surgery.Methods: This observational study included 210 patients undergoing hip fracture surgery from July 2018 to Maj 2020. These 210 patients were alive and had a hemoglobin ≤ 6.5mmol/L on the 3rd postoperative day. In May 2019 a local intravenous iron therapy protocol was implemented and recommended intravenous iron (Monofer ©) if hemoglobin on the 3rd postoperative day was ≤ 6.5 mmol/L. According to treatment of postoperative anemia between 1st and 3rd day post-surgery, the patients were divided into four groups: No treatment (n=52), blood transfusion (n=38), IV Monofer (n=80) and blood transfusion & IV Monofer (n=40). Primary outcome was 30-day mortality post-surgery. The secondary outcome was the impact on hemoglobin level 14-30 days postoperatively. Multivariable Cox regression was used to estimate the 30-day mortality standardized for covariates. Results: Of 210 patients, 17 (8.1%) died within 30-days after surgery. There was a significantly lower mortality among the patients who received IV Monofer compared to those who received no treatment (HR: 0.17, 95% CI: [0.03-0.93], P = 0.041). Among the 86 patients with available hemoglobin measurements within 14 to 30 days post-surgery, there was no significant difference in hemoglobin level between the various treatment groups (mean 6.6 mmol/L, P = 0.1165).Conclusion: IV Monofer on the 3rd postoperative day in older hip fracture patients seemed to reduce 30-day mortality compared with no treatment. No significant differences in hemoglobin levels between 14-30 days post-surgery across treatment groups were found, although this was assessed in a subset of patients with available hemoglobin levels warranting further study. Trial registration: NA

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