Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Histological Findings After Aortic Cross-Clamping in Preclinical Animal Models.

ABSTRACT: Spinal cord ischemic injury and paralysis are devastating complications after open surgical repair of thoracoabdominal aortic aneurysms. Preclinical models have been developed to simulate the clinical paradigm to better understand the neuropathophysiology and develop therapeutic treatment. Neuropathological findings in the preclinical models have not been comprehensively examined before. This systematic review studies the past 40 years of the histological findings after open surgical repair in preclinical models. Our main finding is that damage is predominantly in the grey matter of the spinal cord, although white matter damage in the spinal cord is also reported. Future research needs to examine the neuropathological findings in preclinical models after endovascular repair, a newer type of surgical repair used to treat aortic aneurysms.

SUBMITTER: Awad H

PROVIDER: S-EPMC8783616 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Histological Findings After Aortic Cross-Clamping in Preclinical Animal Models.

Awad Hamdy H Efanov Alexander A Rajan Jayanth J Denney Andrew A Gigax Bradley B Kobalka Peter P Kelani Hesham H Basso D Michele DM Bozinovski John J Tili Esmerina E

Journal of neuropathology and experimental neurology 20211001 10

Spinal cord ischemic injury and paralysis are devastating complications after open surgical repair of thoracoabdominal aortic aneurysms. Preclinical models have been developed to simulate the clinical paradigm to better understand the neuropathophysiology and develop therapeutic treatment. Neuropathological findings in the preclinical models have not been comprehensively examined before. This systematic review studies the past 40 years of the histological findings after open surgical repair in p ...[more]

PMID: 34534333

Similar Datasets

Fluid-structure interaction in aortic cross-clamping: implications for vessel injury.

Project description:Vascular cross-clamping is applied in many cardiovascular surgeries such as coronary bypass, aorta repair and valve procedures. Experimental studies have found that clamping of various degrees caused damage to arteries. This study examines the effects of popular clamps on vessel wall. Models of the aorta and clamp were created in Computer Assisted Design and Finite Element Analysis packages. The vessel wall was considered as a non-linear anisotropic material while the fluid was simulated as Newtonian with pulsatile flow. The clamp was applied through displacement time function. Fully coupled two-way solid-fluid interaction models were developed. It was found that the clamp design significantly affected the stresses in vessel wall. The clamp with a protrusion feature increased the overall Von Mises stress by about 60% and the compressive stress by more than 200%. Interestingly, when the protrusion clamp was applied, the Von Mises stress at the lumen (endothelium) side of artery wall was about twice that of the outer wall. This ratio was much higher than that of the plate-like clamp which was about 1.3. The flow reversal process was demonstrated during clamping. Vibrations, flow and wall shear stress oscillations were detected immediately before total vessel occlusion. The commonly used protrusion clamp increased stresses in vessel wall, especially the compressive stress. This design also significantly increased the stresses on endothelium, detrimental to vessel health. The present findings are relevant to surgical clamp design as well as the transient mechanical loading on the endothelium and potential injury. The deformation and stress analysis may provide valuable insights into the mode of tissue injury during cross-clamping.

| S-EPMC2813350 | biostudies-literature

Robot-assisted mitral valve surgery without aortic cross-clamping: An alternative technique.

Project description: Not available

| S-EPMC8462102 | biostudies-literature

Passive Immunization in Alpha-Synuclein Preclinical Animal Models.

Project description:Alpha-synucleinopathies include Parkinson's disease, dementia with Lewy bodies, pure autonomic failure and multiple system atrophy. These are all progressive neurodegenerative diseases that are characterized by pathological misfolding and accumulation of the protein alpha-synuclein (αsyn) in neurons, axons or glial cells in the brain, but also in other organs. The abnormal accumulation and propagation of pathogenic αsyn across the autonomic connectome is associated with progressive loss of neurons in the brain and peripheral organs, resulting in motor and non-motor symptoms. To date, no cure is available for synucleinopathies, and therapy is limited to symptomatic treatment of motor and non-motor symptoms upon diagnosis. Recent advances using passive immunization that target different αsyn structures show great potential to block disease progression in rodent studies of synucleinopathies. However, passive immunotherapy in clinical trials has been proven safe but less effective than in preclinical conditions. Here we review current achievements of passive immunotherapy in animal models of synucleinopathies. Furthermore, we propose new research strategies to increase translational outcome in patient studies, (1) by using antibodies against immature conformations of pathogenic αsyn (monomers, post-translationally modified monomers, oligomers and protofibrils) and (2) by focusing treatment on body-first synucleinopathies where damage in the brain is still limited and effective immunization could potentially stop disease progression by blocking the spread of pathogenic αsyn from peripheral organs to the brain.

| S-EPMC8961624 | biostudies-literature

Tetramethylpyrazine attenuates spinal cord ischemic injury due to aortic cross-clamping in rabbits.

Project description:BackgroundLower limb paralysis occurs in 11% of patients after surgical procedure of thoracic or thoracoabdominal aneurysms and is an unpredictable and distressful complication. The aim of this study was to investigate the effects of tetramethylpyrazine (TMP), an intravenous drug made from traditional Chinese herbs, on the neurologic outcome and histopathology after transient spinal cord ischemia in rabbits.MethodsForty-five male New Zealand white rabbits were anesthetized with isoflurane and spinal cord ischemia was induced for 20 min by infrarenal aortic occlusion. Animals were randomly allocated to one of five groups (n = 8 each). Group C received no pharmacologic intervention. Group P received intravenous infusion of 30 mg x kg(-1) TMP within 30 min before aortic occlusion. Group T1, Group T2 and Group T3 received intravenous infusion of 15, 30 and 60 mg x kg(-1) TMP respectively within 30 min after reperfusion. In the sham group (n = 5), the animals underwent the same procedures as the control group except infrarental aortic unocclusion. Neurologic status was scored by using the Tarlov criteria (in which 4 is normal and 0 is paraplegia) at 4 h, 8 h, 12 h, 24 h, and 48 h after reperfusion. All animals were sacrificed at 48 h after reperfusion and the spinal cords (L5) were removed immediately for histopathologic study.ResultsAll animals in the control group became paraplegic. Neurologic status and histopathology (48 h) in the Groups P, T2 and T3 were significantly better than those in the control group (P < 0.05). There was a strong correlation between the final neurologic scores and the number of normal neurons in the anterior spinal cord (r = 0.776, P < 0.01).ConclusionTetramethylpyrazine significantly reduces neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion within a certain range of dose.

| S-EPMC107739 | biostudies-literature

Rapamycin inhibits anal carcinogenesis in two preclinical animal models.

Project description:The incidence of anal cancer is increasing especially among HIV-infected persons in the HAART era. Treatment of this cancer is based upon traditional chemoradiotherapeutic approaches, which are associated with high morbidity and of limited effectiveness for patients with high-grade disease. The mammalian target of rapamycin (mTOR) pathway has been implicated in several human cancers, and is being investigated as a potential therapeutic target. In archival human anal cancers, we observed mTOR pathway activation. To assess response of anal cancer to mTOR inhibition, we utilized two newly developed mouse models, one in which anal cancers are induced to arise in HPV16 transgenic mice and the second a human anal cancer xenograft model. Using the transgenic mouse model, we assessed the preventative effect of rapamycin on neoplastic disease. We saw significant changes in the overall incidence of tumors, and tumor growth rate was also reduced. Using both the transgenic mouse and human anal xenograft mouse models, we studied the therapeutic effect of rapamycin on preexisting anal cancer. Rapamycin was found to significantly slow, if not stop, the growth of both mouse and human anal cancers. As has been seen in other cancers, rapamycin treatment led to an activation of the MAPK pathway. These results provide us cause to pursue further the evaluation of rapamycin as a therapeutic agent in the control of anal cancer.

| S-EPMC3058330 | biostudies-literature

Dichloroacetate prevents restenosis in preclinical animal models of vessel injury.

Project description:Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.

| S-EPMC4323184 | biostudies-literature

Radiation-Induced Lung Fibrosis: Preclinical Animal Models and Therapeutic Strategies.

Project description:Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced lung fibrosis, is the most common side effect of radiation therapy. RILI is a complicated process that causes the accumulation, proliferation, and differentiation of fibroblasts and, finally, results in excessive extracellular matrix deposition. Currently, there are no approved treatment options for patients with radiation-induced pulmonary fibrosis (RIPF) partly due to the absence of effective targets. Current research advances include the development of small animal models reflecting modern radiotherapy, an understanding of the molecular basis of RIPF, and the identification of candidate drugs for prevention and treatment. Insights provided by this research have resulted in increased interest in disease progression and prognosis, the development of novel anti-fibrotic agents, and a more targeted approach to the treatment of RIPF.

| S-EPMC7352529 | biostudies-literature

A mouse model of ischemic spinal cord injury with delayed paralysis caused by aortic cross-clamping.

Project description:BackgroundSpinal cord ischemia and paralysis are devastating perioperative complications that can accompany open or endovascular repair surgery for aortic aneurysms. Here, we report on the development of a new mouse model of spinal cord ischemia with delayed paralysis induced by cross-clamping the descending aorta.MethodsTransient aortic occlusion was produced in mice by cross-clamping the descending aorta through a lateral thoracotomy. To establish an optimal surgical procedure with limited mortality, variable cross-clamp times and core temperatures were tested between experiments.ResultsThe onset of paresis or paralysis and postsurgical mortality varied as a function of cross-clamp time and core temperature that was maintained during the period of cross-clamp. Using optimal surgical parameters (7.5-min cross-clamp duration at 33°C core temperature), the onset of paralysis is delayed 24-36 h after reperfusion, and more than 95% of mice survive through 9 weeks after surgery. These mice are further stratified into two groups, 70% (n = 19/27) of mice developing severe hind limb paralysis and the remaining mice showing mild, though still permanent, behavioral deficits.ConclusionThis new model should prove useful as a preclinical tool for screening neuroprotective therapeutics and for defining the basic biologic mechanisms that cause delayed paralysis and neurodegeneration after transient spinal cord ischemia.

| S-EPMC2945453 | biostudies-literature

SGLT2 inhibition improves PI3Kα inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials.

Project description:PurposeAlpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+ /HER2- advanced breast cancer (ABC) (SOLAR-1). Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. We report data from preclinical models and two clinical trials (SOLAR-1 and BYLieve) on Sodium glucose cotransporter 2 inhibitor (SGLT2i) use to improve PI3Kα inhibitor-associated hyperglycemia.MethodsHealthy Brown Norway (BN), mild diabetic Zucker diabetic fatty (ZDF), and Rat1-myr-p110α/HBRX3077 tumor-bearing nude rats treated with alpelisib were analyzed for glucose and insulin control with metformin and dapagliflozin (SGLT2i) and alpelisib efficacy. Hyperglycemia adverse events (AEs) were compared between patients receiving SGLT2i with alpelisib (n = 19) and a propensity score-matched cohort not receiving SGLT2i (n = 74) in both trials.ResultsDapagliflozin and metformin in BN and ZDF rats treated with alpelisib normalized blood glucose and reduced insulin levels. No signs of ketosis or drug-drug interaction were observed when metformin and dapagliflozin was administered with alpelisib. Alpelisib antitumor efficacy was maintained when used with dapagliflozin in tumor-bearing rats. Compared with a matched set of patients without SGLT2i, patients receiving SGLT2i had 4.9 and 6.4 times lower rates of grade ≥ 3 hyperglycemia AEs and hyperglycemia AEs resulting in alpelisib dose adjustments, interruptions, or withdrawals, respectively, and a relative reduction in risk of experiencing these AEs (70.6% and 35.7%).ConclusionThese data suggest adding an SGLT2i can effectively manage hyperglycemia, resulting in fewer alpelisib dose modifications and discontinuations in patients with PIK3CA-mutated HR+ /HER2- ABC (SOLAR-1: NCT02437318; BYLieve: NCT03056755).

| S-EPMC11452482 | biostudies-literature

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm.

Project description:Thoracic aortic aneurysm (TAA) has a prevalence of 0.16-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

| S-EPMC10815651 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data