The entire surgical procedure for each animal was completed within 20 min. SWPA ID 0.18, Wuxi Samini Spring Co., Ltd., Jiangsu, China) was placed around the left CCA to prevent cerebral blood flow (CBF) compensation. MC-0.50-55, Research Instruments SW, Escondido, CA, USA was placed around the right CCA following a published protocol. Both common carotid arteries (CCAs) were exposed through a midline cervical incision, and an ameroid constrictor ring (cat. Ophthalmic ointment was placed on the eyes the surgical area was prepared by trimming the fur and sanitizing the skin with isopropanol pads followed by betadine. Mice were anesthetized with 4–5% isoflurane and maintained under 1–2% isoflurane in a 30% O2:70% N2 mixture and placed on a feedback-controlled heating pad to maintain the body temperature at 37 ☌. Mice were randomized to sham surgery and ameroid constrictor, arterial stenosis (ACAS) surgery groups. We conclude that antibody neutralization of IL-1β is protective from the brain damage caused by chronic, progressive brain hypoperfusion. Over the course of hypoperfusion/injury, grip strength, coordination, and memory-related behavior were not significantly affected by ACAS surgery or antibody treatment. The IL-1β antibody treatment did not significantly affect CBF but largely eliminated grey matter damage and reduced white matter damage caused by ACAS surgery. We observed that ACAS surgery causes a reduction in cerebral blood flow (CBF) of about 30% and grey and white matter damage in and around the hippocampus. In the present study, we induced chronic, progressive brain hypoperfusion in mice using ameroid constrictor, arterial stenosis (ACAS) surgery and tested the efficacy of an IL-1β antibody on the resulting brain damage. Cerebral hypoperfusion leads to a chronic state of brain inflammation with immune cell activation and production of pro-inflammatory cytokines, including IL-1β. Chronic brain hypoperfusion is the primary cause of vascular dementia and has been implicated in the development of white matter disease and lacunar infarcts.
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