IL-1β Antibody Protects Brain from Neuropathology of Hypoperfusion

Abstract

Chronic brain hypoperfusion is the primary cause of vascular dementia and has been implicated in the development of white matter disease and lacunar infarcts. Cerebral hypoperfusion leads to a chronic state of brain inflammation with immune cell activation and production of pro-inflammatory cytokines, including IL-1β. 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. 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. 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. Over the course of hypoperfusion/injury, grip strength, coordination, and memory-related behavior were not significantly affected by ACAS surgery or antibody treatment. We conclude that antibody neutralization of IL-1β is protective from the brain damage caused by chronic, progressive brain hypoperfusion.

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2/SRC pathway in vascular cognitive impairment mice

“…Microglia play a critical role in WMLs and an elevated inflammatory response parallel with WMLs, 59,60 as is shown in our study. Meanwhile, recent studies indicated that pro‐inflammatory activated microglia could exacerbate WMLs 61 and release pro‐inflammatory markers 62,63 . Our research identified a noticeable activation of the hippocampal microglia and enhanced secretion of pro‐inflammatory cytokines in VCI mice, which was reversed by hyperforin treatment.…”

Respiratory syncytial virus infection disrupts pulmonary microbiota and immune barriers to induce microglia phenotype shift

“…Inducible nitric oxide synthase (iNOS), one of the enzymes that produces nitric oxide (NO) from the amino acid l-arginine confers some anti-inflammatory properties that regulate human asthma while IL-1β antibody has some protective effects on the brain from neuropathology of hypoperfusion [29]. An increased phenotypic marker of M1, which are IL-1β and iNOS during RSV infection can cause neurotoxicity and DNA damage respectively [30].…”

Respiratory syncytial virus infection disrupts pulmonary microbiota to induce microglia phenotype shift

“…iNOS is one of the enzymes that produces nitric oxide from the amino acid l ‐arginine confers some pro and anti‐inflammatory biomarkers that regulate human asthma while IL‐1β antibody has some protective effects on the brain from neuropathology of hypoperfusion 23 . An increased phenotypic marker of M1, which are IL‐1β and iNOS during RSV infection can cause neurotoxicity and DNA damage respectively 24 . Microglia affects the immune microenvironment of neurons mainly through the release of effector factors from different phenotypes after activation, thus affecting neuronal survival 25 .…”

“…23 An increased phenotypic marker of M1, which are IL-1β and iNOS during RSV infection can cause neurotoxicity and DNA damage respectively. 24 Microglia affects the immune microenvironment of neurons mainly through the release of effector factors from different phenotypes after activation, thus affecting neuronal survival. 25 Due to the further expression of biomarkers in our study, when Ampicillin is added, Butyrivibrio decreased significantly.…”