title: Microemboli alter the acute stress response and cause prolonged expression of MCP-1 in the hippocampus.
abstract: Microvascular ischemia is linked to cardiovascular disease pathology, as well as alterations in mood and cognition. Ischemia activates the hypothalamic-pituitary-adrenal (HPA) axis and through chronic activation, alters HPA axis function. Dysregulation of the HPA axis can lead to the chronic release of glucocorticoids, a hyper-inflammatory cerebral response, cell damage, and changes in behavior. Although the interactions between injury and HPA axis activity have been established in global ischemia, HPA-related repercussions of diffuse ischemic damage and subsequent inflammation have not been assessed. The current study used a rat model of microsphere embolism (ME) ischemia to test the hypothesis that microvascular ischemia would lead to long term alterations in HPA axis function and inflammatory activity. Furthermore, given the pro-inflammatory nature of chronic stress, we assessed the implications of chronic stress for gene expression of inflammatory factors and key components of the glucocorticoid receptor response, following microvascular ischemia. Results indicated that ME altered the response to an acute stress fourteen days following ME injury and increased hippocampal expression of monocyte chemoattractant protein 1 (Mcp-1) as long as 4 weeks following ME injury, without concomitant effects on gene expression of the glucocorticoid receptor or its co-chaperones. Furthermore, no exacerbative effects of chronic stress exposure were observed following ME injury beyond the effects of ME injury alone. Together, these results indicate that ME injury is sufficient to alter both HPA axis activity and cerebral inflammation for a prolonged period of time following injury.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States; Department of Physiology, Emory University, Atlanta, GA, United States.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Nemeth
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States; Department of Physiology, Emory University, Atlanta, GA, United States. Electronic address: gretchen.neigh@emory.edu.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D020766:Intracranial Embolism / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007511:Ischemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D011965:Receptors, Glucocorticoid; D003345:Corticosterone
keywords: HPA axis; Inflammation; Ischemia; Stress; Vasculature