Surgery-induced Cognitive Dysfunction Research Articles

Experimental insights into age‐exacerbated cognitive dysfunction after peripheral surgery

Here I comment on the recent contribution by Barrientos et al. J. Neurosci. 32, 14641-14648 (2012) addressing treatment possibilities for surgery-induced cognitive dysfunction. It has been over 15 years since the publication of a landmark study that indicated age as a major risk factor for postoperative cognitive dysfunction (POCD) (Moller et al., Lancet 351, 857-861 1998). With increasing life expectancy, surgical procedures conducted in elderly persons are becoming more common. The prevalence of POCD may mean that some patients will exchange the incapacitating condition that led them to surgery in the first instance for another such condition, which has been created by the surgical procedure itself. The report by Barrientos and collaborators (2012) is a timely and welcome study that further examines treatment possibilities for surgery-induced cognitive dysfunction. Future studies should address issues such as intensity and onset of inflammation within the brain and additional treatments possibilities beyond IL-1-ra.

Hydrogen sulfide attenuates surgical trauma-induced inflammatory response and cognitive deficits in mice

BackgroundIt has been increasingly reported that peripheral surgical trauma triggers neuroinflammatory processes associated with postoperative cognitive dysfunction, and that mitigating the neuroinflammatory effects of surgery prevents surgery-induced cognitive dysfunction. Endogenously produced hydrogen sulfide (H2S) has multiple functions in the brain, and an increasing number of studies have demonstrated its anti-inflammatory effects. The present study was designed to investigate the effects of sodium hydrosulfide (NaHS), an H2S donor, on the cognitive impairment of mice as they experience neuroinflammatory changes induced by surgery. MethodsEach mouse received 5 mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection once daily, 3 d before surgery, on the day of surgery, and for 3 d afterward. We assessed cognitive function using a Morris water maze and evaluated expression of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the serum and hippocampus. We performed each test 1, 3, and 7 d after surgery. ResultsHippocampal-dependent memory impairment in mice after surgery was associated with increased serum proinflammatory cytokines, as well as proinflammatory cytokine expression in the hippocampus. Presurgery treatment with NaHS, an H2S donor, significantly attenuated surgery-induced memory impairment and expression of proinflammatory cytokines in the serum and hippocampus. ConclusionsThese findings suggest that intraperitoneal injections of NaHS could significantly mitigate surgery-induced memory impairment in mice, which is strongly associated with reduced levels of serum and hippocampal proinflammatory cytokines.

Systemic inflammation enhances surgery-induced cognitive dysfunction in mice

The activation of the immune system, by either lipopolysaccharide (LPS) administration or surgical trauma, has been shown to be capable of affecting hippocampal function, causing memory impairment. Here, we examined the extent to which LPS-induced infection may aggravate impairment of memory function following orthopaedic surgery. Hippocampal memory function impairment was assessed using fear-conditioning tasks, while IL-1β levels in plasma and hippocampus were measured using ELISA. LPS-induced inflammation disrupted hippocampal memory consolidation as evidenced by reduced contextual freezing time exhibited by infected mice. Likewise, surgery caused hippocampal-dependent memory impairment, which was associated with increased levels of IL-1β both in plasma and hippocampus. However, a sub-pyrogenic dose of LPS alone failed to impair memory function. This dose of LPS, when administered prior to surgery, exacerbated surgery-induced cognitive dysfunction as evidenced by further reduction of contextual freezing time. Also, it caused a concomitant additional increase in the levels of IL-1β in both plasma and hippocampus of those animals. Our data suggest that sub-clinical infection may sensitise the immune system augmenting the severity of post-operative cognitive dysfunction.