Published: 30-12-2011 00:00 | Updated: 26-11-2013 10:29

Surgery affects concentration and memory

[NEWS 30 December 2011] Patientsundergoing surgery and anesthesia can develop a decline in memory and learning a long time afterwards. This has been called postoperative cognitive decline and is a significant problem for patients having surgery. Researchers at Karolinska Institutet and Karolinska University Hospital, in collaboration with groups from the US, have now mapped the signal pathways from the peripheral surgical lesion and into the parts of the brain involved in memory and learning, and have gained a better understanding of how to prevent postoperative cognitive decline.

Lars I ErikssonPhoto: Bildmakarna

Postoperative cognitive decline is particularly common in the first week after surgery, but in ten per cent of adult patients it can persist even longer, that is for up to three months. Although the reason for this impairment of memory and learning capacity remains unclear, it is known that patient-related factors such as age, morbidity and pre-existent cognitive impairments are a significant risk factor.

"In recent years, animal studies have shown that surgery itself can cause distinct changes in the parts of the brain involved in cognitive functions, as the inflammatory response to surgery leads to neuroinflammation-related disruption to cognitive abilities," says Lars I Eriksson, professor of anaesthesiology and intensive care at Karolinska Institutet's Department of Physiology and Pharmacology and doctor at Karolinska University Hospital.

The study, which is now published in the scientific journal Annals of Neurology was initiated by Lars I Eriksson and Niccolo Terrando, and conducted in association with researchers at the University of California, San Francisco in the USA. By studying the neuroinflammatory changes and seeing how they are affected by the introduction of substances that stimulate acetylcholine-dependent inflammatory reflex paths in the peripheral and central nervous system, the researchers have found that one of the side-effects of surgery is damage to the blood-brain barrier.

"We show how the peripheral surgical intervention increases inflammatory proteins, which in turn damage the blood-brain barrier, thus enabling activated immunocompetent blood cells, or macrophages, to pass into the parts of the brain involved in cognitive processes," says Professor Eriksson.

Professor Eriksson also cites studies on genetically modified animals that lack the ability to activate peripheral macrophages, in which no damage to the blood-brain barrier or infiltration of macrophages into the brain has been observed - something that also demonstrates the importance of these cells for the signal pathways to the brain.

"If you give an acetylcholine-like substance with an affinity for an alpha-7 protein, part of the natural anti-inflammatory reflex pathway, prior to surgery, you significantly decrease the levels of inflammatory proteins and the consequent damage to the blood-brain barrier, and thus prevent the infiltration of macrophages into the brain," he says.

The present study also shows that treatment with this selective stimulation of an endogenous inflammatory pathway leads to an almost total normalisation of cognitive capacity during the postoperative period. It thus indicates that the use of new molecular anti-inflammatory mechanisms can prevent postoperative neuroinflammation and the attendant decline in cognitive abilities.

Publication:

Niccolo Terrando, Lars I Eriksson, Jae Kyu Ryu, Ting Yang, Claudia Monaco, Marc Feldman, Malin Jonsson Fagerlund, Israel F Charo, Katerina Akassoglou, Mervy Maze

Resolving postoperative neuroinflammation and cognitive decline

Annals of Neurology, december 2011, DOI: 10.1002/ana.22664

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