| Autor: |
Peterson TC; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Palo Alto, CA, USA.; Department of Psychology, University of North Carolina Wilmington, Wilmington, NC, USA., Lechtenberg KJ; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Palo Alto, CA, USA., Piening BD; Department of Genetics, Stanford School of Medicine, Palo Alto, CA, USA.; Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA., Lucas TA; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Palo Alto, CA, USA., Wei E; Department of Genetics, Stanford School of Medicine, Palo Alto, CA, USA., Chaib H; Department of Genetics, Stanford School of Medicine, Palo Alto, CA, USA., Dowdell AK; Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA., Snyder M; Department of Genetics, Stanford School of Medicine, Palo Alto, CA, USA., Buckwalter MS; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Palo Alto, CA, USA. marion.buckwalter@stanford.edu.; Department of Neurosurgery, Stanford School of Medicine, Palo Alto, CA, USA. marion.buckwalter@stanford.edu.; Department of Neurology and Neurological Sciences and Department of Neurosurgery, Stanford University, P209 MSLS Building, 1201 Welch Road, Stanford, CA, 94305, USA. marion.buckwalter@stanford.edu. |
| Abstrakt: |
Obesity is associated with chronic peripheral inflammation, is a risk factor for stroke, and causes increased infarct sizes. To characterize how obesity increases infarct size, we fed a high-fat diet to wild-type C57BL/6J mice for either 6 weeks or 15 weeks and then induced distal middle cerebral artery strokes. We found that infarct expansion happened late after stroke. There were no differences in cortical neuroinflammation (astrogliosis, microgliosis, or pro-inflammatory cytokines) either prior to or 10 h after stroke, and also no differences in stroke size at 10 h. However, by 3 days after stroke, animals fed a high-fat diet had a dramatic increase in microgliosis and astrogliosis that was associated with larger strokes and worsened functional recovery. RNA sequencing revealed a dramatic increase in inflammatory genes in the high-fat diet-fed animals 3 days after stroke that were not present prior to stroke. Genetic pathways unique to diet-induced obesity were primarily related to adaptive immunity, extracellular matrix components, cell migration, and vasculogenesis. The late appearance of neuroinflammation and infarct expansion indicates that there may be a therapeutic window between 10 and 36 h after stroke where inflammation and obesity-specific transcriptional programs could be targeted to improve outcomes in people with obesity and stroke. |
Full text from SpringerLink