Altered Jagged1-Notch1 Signaling in Enhanced Dysfunctional Neovascularization and Delayed Angiogenesis After Ischemic Stroke in HFD/STZ Induced Type 2 Diabetes Rats

Abstract

Diabetes exacerbates brain damage in cerebral ischemic stroke. Our previous study has demonstrated that after cerebral ischemia, type 2 diabetes rats displayed worse neurological outcomes, larger cerebral infarction and severer blood-brain barrier disruption. However, our knowledge of the mechanisms of how diabetes impacts the cerebrovascular repair process is limited. This study was aimed to characterize structural alterations and potential mechanisms in brain microvessels before and after ischemic stroke in type 2 diabetic rats treated with high-fat diet and streptozotocin (HFD/STZ). Furtherly, we tested our hypothesis that dysregulated intercellular Jagged1-Notch1 signaling was involved in the dysfunctional cerebral neovascularization both before and after ischemic stroke in HFD/STZ rats. In our study, we found increased yet dysfunctional neovascularization with activated Jagged1-Notch1 signaling in the cerebrovasculature before cerebral ischemia in HFD/STZ rats compared with non-diabetic rats. Furthermore, we observed delayed angiogenesis as well as suppressed Jagged1-Notch1 signaling after ischemic stroke. Our results elucidate the potential mechanisms underlying diabetes-related cerebral microvasculature dysfunction after ischemic stroke.

Exercise rescues cognitive impairment through the fibrinogen pathway in diabetes

“…One limitation of this study is that we didn't use the transgenic animal model of brinogen and that will be our future research plan. What' more, although STZ induction method is a recognized model of diabetes, it can't fully represent the complex pathophysiological process of clinical cases [32].…”

Bailing capsule (Cordyceps sinensis) ameliorates renal triglyceride accumulation through the PPARα pathway in diabetic rats

“…All of the animal procedures were approval by the Animal Care Committee of the Peking Union Medical Hospital Animal Ethics Committee (Project XHDW-2015-0051, 15 February 2015). DN rat model was developed by a high-fat diet (HFD) feeding combined with low dosage of streptozotocin (STZ) injection, according to previous studies ( Danda et al, 2005 ; Liu et al, 2020 ; Guo et al, 2021 ). All rats were randomly divided into a normal control group ( n = 8) fed a standard diet (SD, fat content, 10 kcal %, D12450B, Research Diets Inc., New Brunswick, NJ) and a DN model group ( n = 24) fed a HFD (fat content, 60 kcal %, D12492, Research Diets Inc., New Brunswick, NJ), respectively.…”

“…All of the animal procedures were approval by the Animal Care Committee of the Peking Union Medical Hospital Animal Ethics Committee (Project XHDW-2015-0051, 15 February 2015. DN rat model was developed by a high-fat diet (HFD) feeding combined with low dosage of streptozotocin (STZ) injection, according to previous studies (Danda et al, 2005;Liu et al, 2020;Guo et al, 2021). All rats were randomly divided into a normal control group (n = 8) fed a Acox1, acyl-CoA oxidase 1; Ppara, peroxisome proliferator activated receptor alpha; Scd, stearoyl-CoA desaturase; Fasn, fatty acid synthase.…”

Exploring Chinese herbal medicine for ischemic stroke: insights into microglia and signaling pathways

“…et al, 2021 ; LI et al, 2022 ). Furthermore, Guo et al ( GUO Z. et al, 2021 ) have discovered that Notch can activate microglia by mediating the ligand Jagged1, leading to the secretion of pro-inflammatory cytokines.…”