β2-Microglobulin exacerbates neuroinflammation, brain damage, and cognitive impairment after stroke in rats

beta 2-Microglobulin (beta 2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of beta 2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of beta 2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that beta 2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit beta 2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased beta 2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha were also effectively inhibited by beta 2M silencing. These findings suggest that beta 2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.