Abstract

Introduction: Obesity is a risk factor for stroke and diet-induced obesity is the most common type of obesity in humans. Yet, the effects of high fat diet (HFD) on neurovascular function and the extent of ischemic brain injury after ischemic stroke are not well understood. Previously we showed that HFD worsens functional hyperemia, vascular function and short-term (24 h) outcomes of ischemic brain injury induced by 3/21 h middle cerebral artery occlusion (MCAO)/reperfusion. The goal of this study is to test the hypotheses that HFD beginning early in life will exacerbate vascular injury and worsen long-term outcomes after focal cerebral ischemia. Methods: Starting at 4 weeks, Wistar rats were fed control (CD) or HFD diet for 8 weeks. The outcomes of cerebral ischemia were evaluated after 90 min MCAO and 5 d reperfusion by measuring neurological deficit, infarct size and hemorrhagic transformation (HT) frequency and severity. The sham groups were treated with same diet and surgical process without artery occlusion. Results: The HFD group had significantly increased body weight and adiposity. In MCAO animals, the infarct volume (37.02 ± 3.68% vs. 19.25 ± 5.52%, p<0.05), HT occurrence (5 out of 7 vs. 2 out of 8) and excess hemoglobin (100.9 ± 55.8 vs. 18.6 ± 4.7 mg/g protein) were greater in the HFD group. After ischemia and reperfusion, the HFD animals showed worse neurological function compared to the CD group. There was no difference between the sham groups. Conclusion and Translational Impact: These results indicate that the HFD started in the early life time lowers the threshold of ischemia to induce HT, exacerbates neurovascular injury and worsens the long term outcomes of focal cerebral ischemia. Given that obesity and stroke incidences are on the rise in young population, diet control should be implemented early to prevent and/or reduce ischemic brain injury.

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