Abstract
Aging is a major risk factor for developing postoperative cognitive dysfunction. Neuroinflammatory processes, which can play a causal role in the etiology of postoperative cognitive dysfunction, are potentiated or primed as a function of aging. Here we explored whether exposure to a microorganism with immunoregulatory and anti-inflammatory properties, Mycobacterium vaccae NCTC 11659 (M.vaccae), could ameliorate age-associated neuroinflammatory priming. Aged (24months) and adult (3months) male F344XBN rats were immunized with heat-killed M.vaccae (3 injections, once per week) before undergoing a laparotomy or anesthesia control procedure. Aged, but not young rats, showed postoperative learning/memory deficits in a fear-conditioning paradigm. Importantly, M.vaccae immunization protected aged rats from these surgery-induced cognitive impairments. M.vaccae immunization also shifted the aged proinflammatory hippocampal microenvironment toward an anti-inflammatory phenotype. Furthermore, M.vaccae immunization reduced age-related hyperinflammatory responses in isolated hippocampal microglia. Overall, our novel data suggest that M.vaccae can induce an anti-inflammatory milieu in the aged brain and thus mitigate the neuroinflammatory and cognitive impairments induced by surgery.
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