NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice

Ll, Qiu; Mh, Ji; Zhang, H; Jj, Yang; Xr, Sun; Tang, Hui; Wang, J; Wx, Liu

doi:10.1016/j.bbi.2015.08.002

Cited by 109 publications

(102 citation statements)

References 42 publications

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“…BDNF is a key signaling molecule involved in a wide range of central functions and neuronal plasticity, including modulatory actions in the hippocampus of relevance to learning, memory, neurogenesis, and mood control (89)(90)(91)(92)(93). Memory impairment after surgery has also been associated with reduced BDNF expression (94)(95)(96)(97). Conditional knockout of BDNF in the forebrain impairs hippocampal-dependent learning in mice (98,99).…”

Section: Discussionmentioning

confidence: 99%

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pain is a critical component hindering recovery and regaining of function after surgery, particularly in the elderly. Understanding the role of pain signaling after surgery may lead to novel interventions for common complications such as delirium and postoperative cognitive dysfunction. Using a model of tibial fracture with intramedullary pinning in male mice, associated with cognitive deficits, we characterized the effects on the primary somatosensory system. Here we show that tibial fracture with pinning triggers cold allodynia and up-regulates nerve injury and inflammatory markers in dorsal root ganglia (DRGs) and spinal cord up to 2 wk after intervention. At 72 h after surgery, there is an increase in activating transcription factor 3 (ATF3), the neuropeptides galanin and neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), as well as neuroinflammatory markers including ionized calcium-binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the fractalkine receptor CX3CR1 in DRGs. Using an established model of complete transection of the sciatic nerve for comparison, we observed similar but more pronounced changes in these markers. However, protein levels of BDNF remained elevated for a longer period after fracture. In the hippocampus, BDNF protein levels were increased, yet there were no changes in Bdnf mRNA in the parent granule cell bodies. Further, c-Fos was down-regulated in the hippocampus, together with a reduction in neurogenesis in the subgranular zone. Taken together, our results suggest that attenuated BDNF release and signaling in the dentate gyrus may account for cognitive and mental deficits sometimes observed after surgery.postoperative pain | nerve injury | memory | delirium | neurogenesis

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Section: Discussionmentioning

confidence: 99%

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Through a combination of retrospective human studies, small prospective biomarker stud- ies, and experiments in animals, it has been suggested that durable consequences of both anesthesia and surgery occur, and that these intersect with the normal processes of aging, and the abnormal processes of chronic neurodegeneration. It is highly likely that inflammatory cascades are at the heart of this intersection (16)(17)(18)(19)(20). In preclinical studies, it has been suggested that neuroinflammation drives early POCD, whereas resolution of neuroinflammation could allow reversal of POCD (20).…”

Section: Mechanisms Underlying Pocdmentioning

confidence: 99%

Postoperative Cognitive Dysfunction: Knowns and Unknowns

Ji¹,

Su²,

Yang³

2017

J Anesth Perioper Med

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Aim of review: The aim of this review was to summarize and discuss current status and challenges in our understanding of the diagnosis, risk factors, pathophysiologic mechanisms, and preventions for postoperative cognitive dysfunction (POCD). Method: We searched and reviewed the articles about POCD published in the past 2 decades using PubMed and Google Scholar. Recent findings: POCD affects a wide variety of cognitive domains, including attention, memory, executive function and speed of information processing, with the deficits in memory and a reduced ability to handle intellectual challenges being most obvious. The causes of POCD are thought to be multifactorial and may include the preoperative health status of the patient, the patients' preoperative level of cognition, perioperative events related to the surgery itself, and possible neurotoxic effects of anesthetic agents. There are many controversies about POCD, from how it is measured to how long it lasts, to its precise implications for patients, and whether POCD is linked to a long-term risk of developing dementia. Summary: POCD is a topic of special importance in the geriatric surgical population. Unfortunately, no therapeutic interventions are available to prevent the onset of POCD, strategies for management of these patients should be a multimodal approach involving close cooperation between the anesthesiologist, surgeon, geriatricians, and family members to promote early rehabilitation and avoid loss of independence in these patients. Future researches focusing on the mechanisms involved in POCD are critical for better understanding and management of this cognitive dysfunction after surgery.

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“…However, it has become more widely accepted that although microglial activation is necessary and crucial for host defense and neuron survival, the over-activation of microglia results in deleterious and neurotoxic consequences (21). Therefore, understanding the causes and defining the characteristics of deleterious microglia activation in POCD have become a recent focus of researches (5). Although direct blocking of pro-inflammatory cytokines signaling in the brain of aged animals is reported to improve surgery-induced neuroinflammation and behavioral impairments, it should be noted that cytokines have dual roles in sustaining the innate immune response and key physiological processes, including synaptic plasticity and tissue healing (33).…”

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confidence: 99%

“…It occurs not only after cardiac surgery but also non-cardiac surgery (e.g., abdominal and orthopedic surgery) or even noninvasive procedures with sedation (2)(3)(4)(5). In fact, anesthesia and surgery-induced longlasting cognitive deficits has gained significant public concerns over the last decade because it is associated with poor patient outcomes, including increased hospital stay, reduced quality of life, loss of social dependence, and increased mortality (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%