High-Fat Diet Aggravates Cerebral Infarct, Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Abstract

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.

Body mass index, blood glucose, and mortality in patients with ischemic stroke in the intensive care unit: A retrospective cohort study

“…Studies have demonstrated that increased fat mass can provoke disorders of glucose metabolism by an array of pathways ( Song et al, 2006 ; King, 2008 ; Stienstra et al, 2010 ). In another experimental study, it is also reported that a high-fat diet could induce hyperglycemia and aggravate the growth of cerebral infarct volume ( Grisotto et al, 2021 ). In our research, we found that the excessive BMI group exactly had a higher blood glucose concentration in the first 24 h, and the level of blood glucose was also independently linked to lower 30-day mortality, but irrelevant to 90-day and 1-year mortality.…”

Prognostic Significance of Admission Glucose Combined with Hemoglobin A1c in Acute Ischemic Stroke Patients with Reperfusion Therapy

“…It has been demonstrated that diabetes is related to cerebral small vessel disease, which may impair the brain’s ability to compensate for acute ischemic insults [ 28 ]. A recent study involving a stroke model in mice with impaired glucose tolerance demonstrated that chronic hyperglycemia is significantly associated with larger infarct volume [ 29 ] and this may result in a worse outcome at 3 months [ 30 ]. In another study, researchers found that chronic pre-stroke hyperglycemia affected middle cerebral artery blood flow velocity during recovery, which might impact the functional outcomes of patients [ 31 ].…”

Isoflurane Attenuates Cerebral Ischaemia–Reperfusion Injury via the TLR4-NLRP3 Signalling Pathway in Diabetic Mice

“…Diabetes is characterized by chronic systemic inflammation that causes an immune response and then leads to microvascular dysfunction [ 5 ]. Studies have shown that diabetes worsens neurological damage after stroke [ 29 , 30 ]. Our research also confirmed that diabetes exacerbated CIRI and worsened ischaemic stroke outcomes.…”