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

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 increasedVCAM-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.