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1.
PLoS One ; 13(10): e0198709, 2018.
Article in English | MEDLINE | ID: mdl-30325927

ABSTRACT

Functional impairment after brain ischemia results in part from loss of neuronal spines and dendrites, independent of neuronal death. Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin that form in neuronal processes (neurites) under conditions of ATP depletion and oxidative stress, and which cause neurite degeneration if not disassembled. ATP depletion and oxidative stress occur with differing severity, duration, and time course in different ischemic conditions. Here we evaluated four mouse models of brain ischemia to define the conditions that drive formation of cofilin-actin rods. Three of the models provide early reperfusion: transient middle cerebral artery occlusion (MCAo), transient bilateral common carotid artery occlusion (CCAo), and cardiac arrest / cardiopulmonary resuscitation (CA/CPR). Early reperfusion restores ATP generating capacity, but also induces oxidative stress. The fourth model, photothrombotic cortical infarction, does not provide reperfusion. Cofilin-actin rods were formed in each of these models, but with differing patterns. Where acute reperfusion occurred, rod formation was maximal within 4 hours after reperfusion. Where infarction occurred, rods continued to form for at least 24 hours after ischemic onset, and extended into the adjacent non-ischemic tissue. Interventions that limit cofilin-actin rod formation may help to preserve integrity of neuronal processes in permanent ischemia.


Subject(s)
Actins/metabolism , Brain Ischemia/metabolism , Cofilin 1/metabolism , Protein Aggregation, Pathological/metabolism , Actins/analysis , Actins/ultrastructure , Animals , Brain Ischemia/pathology , Cells, Cultured , Cofilin 1/analysis , Cofilin 1/ultrastructure , Disease Models, Animal , Male , Mice, Inbred C57BL , Neurons/metabolism , Neurons/pathology , Oxidative Stress , Protein Aggregation, Pathological/pathology
2.
Shock ; 49(3): 317-325, 2018 03.
Article in English | MEDLINE | ID: mdl-28885386

ABSTRACT

PURPOSE: We assessed the usefulness of the delta neutrophil index (DNI), reflecting immature granulocytes, to stratify risk for developing contrast-induced nephropathy (CIN) in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) in a clinical setting. METHODS: This study retrospectively analyzed prospective data of eligible adult patients admitted to the emergency department (ED) with STEMI followed by PCI. We determined DNI at multiple time points and analyzed the development of CIN and in-hospital mortality according to CIN incidence. RESULTS: Overall, 564 patients with STEMI followed by PCI were included. Of these, 58 patients (10.3%) had CIN. Areas under the curve for predictability of CIN using the DNI within 2 h after PCI (I) and 24 h on ED admission (24) among patients with CIN were 0.775 (P < 0.001) and 0.751 (P < 0.001), respectively. Multivariable logistic regression demonstrated that increased DNI values at time I (odds ratio [OR], 1.632; 95% confidence interval [CI], 1.357-1.964; P < 0.001) and time 24 (OR, 1.503; 95% CI, 1.272-1.777; P < 0.001) were strong independent factors for predicting CIN among patients with STEMI who underwent PCI. Increasing predictability of CIN was closely associated with DNI more than 1.8% on ED admission (OR, 12.494; 95% CI, 6.540-23.87; P < 0.001) and more than 1.9% at time 24 (OR, 10.45; 95% CI, 5.769-18.928; P < 0.001). CONCLUSION: The DNI is easily obtained as part of the complete blood count measurement without requiring additional cost or time. High DNI independently predicts the development of CIN in patients with acute STEMI followed by PCI.


Subject(s)
Contrast Media/adverse effects , Kidney Diseases , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Aged , Aged, 80 and over , Contrast Media/administration & dosage , Female , Hospital Mortality , Humans , Kidney Diseases/blood , Kidney Diseases/chemically induced , Kidney Diseases/etiology , Kidney Diseases/mortality , Leukocyte Count , Male , Middle Aged , Retrospective Studies , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/surgery
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