PubMed Health⌕ Search

PubMed · 15920636

Cognitive dysfunction after cardiac surgery: revisiting etiology.

Abstract

Cognitive dysfunction remains a frequent complication of cardiac surgery. Despite many years of research, few preventive strategies and no definitive therapeutic options exist for the management of this troublesome clinical problem. This shortcoming may be secondary to an incomplete understanding of the pathophysiology and etiology of cognitive loss after cardiac surgery; a better understanding of the etiology is essential to finding new therapies. The etiology of cognitive dysfunction after cardiac surgery is multifactorial and includes cerebral microembolization, global cerebral hypoperfusion, systemic and cerebral inflammation, cerebral temperature perturbations, cerebral edema, and possible blood-brain barrier dysfunction, all superimposed on genetic differences in patients that may make them more susceptible to injury or unable to repair from injury once it has occurred. This review expands on these potential etiologies in detailing the evidence for their existence.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hilary P Grocott, H Mayumi Homi, Ferenc Puskas. 2005. Cognitive dysfunction after cardiac surgery: revisiting etiology.. https://doi.org/10.1177/108925320500900204

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Protective effects of liver-derived apolipoprotein A1 against heat stress-induced hypothalamic lipid metabolism and blood-brain barrier integrity.

Heat stress (HS), a prevalent occupational and environmental hazard, has increasingly been recognized as a major contributor to multiple physiological disorders. The hypothalamus, a key regulator of thermoregulation and endocrine signaling, is especially susceptible to metabolic and inflammatory disturbances induced by HS. This study investigates the interplay among lipid metabolism, blood-brain barrier (BBB) integrity, and neuroinflammation in the hypothalamus under HS conditions, with a specific focus on apolipoprotein A1 (APOA1) as a potential protective factor. To achieve this, we integrated proteomic and lipidomic analyses with experimental validation in porcine and murine models. Proteomic analysis identified 266 differentially expressed proteins (DEPs) in the hypothalamus following HS, with significant enrichment in lipid metabolism pathways-especially glycerophospholipid (GP) metabolism-in which APOA1 displayed a marked increase. Lipidomic profiling further revealed HS-induced disruptions in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) metabolism. Additionally, blood-brain barrier integrity was compromised, as evidenced by increased perivascular IgG extravasation, reduced pericyte coverage, and decreased expression of tight junction proteins ZO-1 and Occludin. HS also triggered pronounced neuroinflammation, characterized by elevated levels of iNOS, GFAP, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Notably, administration of D-4F, an APOA1 mimetic peptide, alleviated blood-brain barrier damage, reduced neuroinflammation, and preserved synaptic integrity, thereby suggesting a neuroprotective role for APOA1 in HS-induced hypothalamic dysfunction. These findings underscore the critical role of lipid metabolism in maintaining hypothalamic homeostasis under HS conditions and position APOA1 as a key regulator with potential therapeutic implications for mitigating HS-related neuroinflammatory and metabolic disturbances.

Blood-Brain Barrier↗

Chemical modification of therapeutic drugs or drug vector systems to achieve targeted therapy: looking for the grail.

Most therapeutic drugs distribute to the whole body, which results in general toxicity and poor acceptance of the treatments by patients. The targeted delivery of chemotherapeutics to defined cells, either stromal or cancer cells in cancer lesions, or defined inflammatory cells in immunological disorders, is one of the main challenges and a very active field of research in the development of treatment strategies to minimize side-effects of drugs. Disease-associated cells express molecules, including proteases, receptors, or adhesion molecules, that are different or differently expressed than their normal counterparts. Therefore one goal in the field of targeted therapies is to develop chemically derivatized drugs or drug vectors able to target defined cells via specific recognition mechanisms and also able to overcome biological barriers. This article will review the approaches which have been explored to achieve these goals and will discuss in more detail three examples (i) the use of nanostructures to take advantage of increased vascular permeability in some human diseases, (ii) the targeting of therapeutic drugs to an organ, the brain, protected against foreign molecules by the blood-brain barrier, and (iii) the use of the folate receptor to target either tumor cells or activated macrophages.

Blood-Brain Barrier↗