Abstract # 3175 Mycobacterium vaccae immunization protects aged rats from surgery-elicited neuroinflammation and cognitive dysfunction

Abstract

Advanced age is a major risk factor for developing postoperative cognitive dysfunction (POCD). Age-related neuroinflammatory “priming” may contribute to POCD: peripheral immune stimuli (e.g., infection or surgery) cause exaggerated pro-inflammatory responses in the aged brain that can elicit pathology. Exposure to micro-organisms with immunoregulatory and anti-inflammatory properties may be a promising strategy to quell neuroinflammatory priming. We hypothesized that immunization with Mycobacterium vaccae (M. vaccae; NCTC11659) would reduce neuroinflammation and cognitive impairments in aged rats post-surgery. Aged (24mos) and adult (3mos) male F344XBN rats received subcutaneous injections of heat-killed M. vaccae (3 injections, once per week) and then 5 days following the final M. vaccae injection rats underwent a laparotomy or sham (anesthesia control) procedure. Three days post-surgery, rats were trained in a fear conditioning paradigm or tissue was collected. Aged (but not young) rats showed post-operative memory deficits. Prophylactic treatment with M. vaccae protected aged rats from surgery induced-cognitive impairments. Furthermore, M. vaccae treatment shifted the aged pro-inflammatory hippocampal microenvironment (increased IL-1beta and NFKBIA) towards an anti-inflammatory phenotype (increased IL-4 and Arg1). Microglia may mediate the anti-inflammatory effects of M. vaccae in the brain: prior in vivo treatment with M. vaccae reduced hyperinflammatory responses to ex vivo lipopolysaccharide in microglia isolated from aged rats. Overall, our novel data suggest that M. vaccae can re-direct a primed neuroimmune environment in aged rats and prevent POCD.