Anti-VCAM-1 Ameliorates the Exacerbated Neuroinflammation Response and Improves Function Recovery [TCP2.1][JH2.2][HJT2.3][PTC2.4]in Diet-Induced Obese Mice After Stroke
Description
People who consume high-fat diets (HFD) and obese are [PTC17.1]over twice as likely to experience a stroke. We have demonstrated [PTC18.1]that high-fat diet (HFD)-fed animals exhibited worsened behavioral deficits, expanded infarcts, and a 4-fold increase in microglia/macrophage coverage compared to animals fed a control diet following stroke[PTC19.1]. HFD-fed animals also exhibit heightened expression of vascular cellular adhesion molecule-1 (VCAM-1) – a molecule crucial for the transmigration of peripheral immune cells[PTC20.1] to cross the blood brain barrier. Past research suggests blocking VCAM-1 reduced microglia activation and improved cognitive deficits in older-aged animals[PTC21.1]. We aimed to determine whether blocking VCAM-1 reduced the neuroinflammatory response and improved functional recovery in HFD-fed animals following stroke. Mice were fed a 60% kCal fat diet or 10% control diet for six weeks prior to stroke. Following stroke, animals were administered either 9 mg/kg of VCAM-1 or control treatment and then assessed on common motor behavior tasks prior to and 1-, 3-, 7-, 14-, and 28 days post-stroke. Additionally, we measured infarct volume (Neun) and macrophage/microglia and astrocyte coverage at acute and chronic timepoints (3- and 29 days) post-stroke. We confirmed after the amelioration of increasedVCAM-1 HFD-fed animals demonstrated improved functional recovery as well as reduced macrophage/microglia and astrocyte coverage, and prevented the increase in infarct expansion compared to HFD-fed animals given the control treatment. Considering the limited treatment options available and the high rates of people with obesity to have a stroke, 𝛼VCAM-1 may serve as a potential intervention for reducing infarct expansion, neuroinflammation, and improve functional recovery.
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Model of obesity and stroke (dMCAO and photothrombotic), treatment with anti vascular cellular adhesion molecule in male and female mice. Reduce macrophage and astrocyte coverage, reduce infarct expansion, improve outcomes in female mice.