Surgery Upregulates High Mobility Group Box‐1 and Disrupts the Blood–Brain Barrier causing Cognitive Dysfunction in Aged Rats

He, Huijuan; Wang, Yi; Yuan, Long; Duan, Kai-Ming; Yan, Xinfeng; Liao, Qin; Liao, Yan; Tong, Jianbin; Terrando, Niccolò; Ouyang, Wen

doi:10.1111/cns.12018

Cited by 164 publications

(132 citation statements)

References 49 publications

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“…The MWM test was used to evaluate the learning and memory of rats. A computerized video track system (Logitech, Suzhou, China) was used to record the movement of the rats in the water maze by following a previous method (13). Briefly, a transparent circular platform was placed below the water surface of the southeast quadrant in a circular black pool.…”

Section: Methodsmentioning

confidence: 99%

“…These showed that ROCK2 was closely involved in the neurotoxicity of sevoflurane. Neurotoxicity of anesthetics was well reported in aged animals (13)(14)(15), natal animals (15) and cultured neurons (16). Yan et al (17) showed that the isoflurane-induced decrease of nNOS is closely correlated with the cognitive impairment in aged rats.…”

Section: Rhoa and Rock2 Upregulation Of Rat Hippocampus Is Involved Imentioning

confidence: 99%

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Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7–9

Han

Tang

et al. 2015

Biomedical Reports

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Abstract. The aim of the present study was to investigate the roles of Rho protein A (RhoA) and Rho kinases 2 (ROCK2) in the memory dysfunction of adult rats exposed to sevoflurane at postnatal days 7-9 (P7-9). One-week-old Sprague-Dawley rats were divided into four groups known as C, S1, S3 and F. Rats in the S1 (2 h at P7) and S3 groups (2 h/day at P7-9) were exposed to sevoflurane. The rats in the F group were treated with the ROCK2 inhibitor and subsequent sevoflurane exposure (2 h/day at P7-9). The rats in the C group received no sevoflurane. The protein levels of RhoA, ROCK2 and cleaved caspase-3 (Cl-Csp3) in the adult hippocampus were assessed by western blot analysis. Learning and memory of rats at postnatal 45-50 days (P45-50) were detected by the Morris water maze (MWM) test. During the training of MWM, the latency and distance of rats in the S3 group were significantly longer than that of the C group (P<0.05, respectively). In the probe test, the percentages of time and distance in the target quadrant for the S3 group were evidently less than that of the C group (P<0.05). There was no significant difference in the behaviors between the C and S1 groups (P>0.05, respectively). Corresponding to the behavioral changes, the levels of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S3 group significantly increased, compared to that of the C and S1 groups (P<0.05). Additionally, the ROCK2 inhibitor clearly decreased ROCK2 and Cl-Csp3 expression and shortened the latency during the training (P<0.05, P46-49 respectively) and probe test (P<0.05) in the F group, compared to that of the S3 group. Compared to the C group, the expression of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S1 group had no significant difference (P>0.05). Multiple inhalation of sevoflurane can induce neurotoxicity and memory dysfunction. RhoA and ROCK2 played important roles in the impairment of learning and memory of adults rats exposed to sevoflurane at the postnatal early stage.

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Section: Methodsmentioning

confidence: 99%

Section: Rhoa and Rock2 Upregulation Of Rat Hippocampus Is Involved Imentioning

confidence: 99%

Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7–9

Han

Tang

et al. 2015

Biomedical Reports

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“…Co-application of multiple anesthetics (midazolam, nitrous oxide and isoflurane) in 7-day old mice caused widespread apoptosis and degenerative changes in central nervous system and subsequent impairment of learning and memory in their adulthood (Jevtovic-Todorovic et al, 2003). In aged rats, isoflurane anesthesia induced weak and temporary cognitive deficit (He et al, 2012). Surgical trauma plus anesthesia, especially major surgery, causes more severe POCD.…”

Section: Introductionmentioning

confidence: 99%

“…Surgical trauma plus anesthesia, especially major surgery, causes more severe POCD. Numerous reports showed that splenectomy, which greatly alters circular system and immune system, resulted in severe cognitive dysfunction in elder rats and mice He et al, 2012;Kamer et al, 2012). Thus, splenectomy is frequently used as major surgery trauma in research involving POCD (Wan et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice

Qian

Zhang

Liu

et al. 2015

European Journal of Pharmacology

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“…Peripheral cytokines, including alarmins like HMGB-1, mediate and facilitate the migration of macrophages into the brain parenchyma through activation of TNF-α/NF-κB signaling pathway and impairing BBB function, which may consequently affect memory and cognitive function (30,53). HMGB-1 has recently been shown to be associated with BBB dysfunction after abdominal surgery and its effect on macrophages have been proven to be related to the processes of surgery-induced cognitive decline and long-term neurocognitive function after sepsis (39,40,54). Aside from a direct effect of pro-inflammatory cytokines on the endothelium, comorbidities including advanced age, systemic diseases, and infections can further impact on the BBB integrity and permeability (55).…”

Section: Volume 1 November 2014mentioning

confidence: 99%

The Role of Inflammation in Postoperative Cognitive Dysfunction

Xu¹,

Yang²,

Terrando³

2014

J Anesth Perioper Med

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Aim of review:Postoperative cognitive dysfunction (POCD) is a common complication following surgery, especially in the elderly population. Surgery exposes patients to extensive trauma, blood loss, and tissue injury, all of which contribute to an inflammatory response. In recent years, inflammation has been shown to be a key contributor to the pathogenesis of cognitive decline and neuroinflammatory processes, both in animal models and initial clinical observations. Method: We review the recent literatures on the proposed mechanisms whereby peripheral trauma leads to cognitive impairments and some of the new neuroprotective strategies that may be implemented to prevent neuroinflammation and POCD. Recent findings: Changes in pro-inflammatory cytokines, alarmins, macrophage activation and blood-brain barrier (BBB) dysfunction have been proven to be related to the pathogenesis of cognitive decline using a variety of models, reagents, and technologies. Strategies to harness these pathways through anti-inflammatory and pro-resolving strategies show remarkable effects in modulating neuronal function, synaptic plasticity, glia activity and memory processes. Summary: Further studies are needed to better identify the patients at higher risk for cognitive decline in the postoperative period and which interventions may be suitable for translation and new clinical trials.

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Surgery Upregulates High Mobility Group Box‐1 and Disrupts the Blood–Brain Barrier causing Cognitive Dysfunction in Aged Rats

Abstract: HMGB1 and RAGE signaling appear pivotal mediators of surgery-induced cognitive decline and may contribute to the changes in BBB permeability after peripheral surgical trauma.

Cited by 164 publications

References 49 publications

Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7–9

Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7–9

Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice

The Role of Inflammation in Postoperative Cognitive Dysfunction

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