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Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats.
CNS Neurosci Ther 2012; 18(12):994-1002CN

Abstract

AIM

Postoperative cognitive dysfunction (POCD) is a growing and largely underestimated problem without defined etiology. Herein, we sought to determine the relationship between cognitive decline, blood-brain barrier (BBB) permeability, and inflammation, namely high mobility group box-1 (HMGB1), after surgery in aged rats.

METHODS

Aged rats were randomly assigned as surgery group (n = 45, splenectomy under general anesthesia), anesthesia (n = 45, 2% isoflurane for 2 h), and naïve control (n = 15). Markers of inflammation were measured in plasma and brain. Blood-brain barrier ultrastructure and permeability were measured by transmission electron microscope (TEM) and IgG immunohistochemistry. Cognitive function was assessed in a reversal learning version of the Morris water maze (MWM).

RESULTS

Surgical trauma under general anesthesia caused distinct changes in systemic and central proinflammatory cytokines. Levels of HMGB1 and the receptor for advanced glycation end products (RAGE) were significantly upregulated in the hippocampus of operated animals. Immunohistochemistry and TEM showed BBB disruption induced by surgery and anesthesia. These molecular changes were associated with cognitive impairment in latency with the MWM up to postoperative day 3.

CONCLUSIONS

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.

Authors+Show Affiliations

Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23078219

Citation

He, Hui-Juan, et al. "Surgery Upregulates High Mobility Group Box-1 and Disrupts the Blood-brain Barrier Causing Cognitive Dysfunction in Aged Rats." CNS Neuroscience & Therapeutics, vol. 18, no. 12, 2012, pp. 994-1002.
He HJ, Wang Y, Le Y, et al. Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther. 2012;18(12):994-1002.
He, H. J., Wang, Y., Le, Y., Duan, K. M., Yan, X. B., Liao, Q., ... Ouyang, W. (2012). Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neuroscience & Therapeutics, 18(12), pp. 994-1002. doi:10.1111/cns.12018.
He HJ, et al. Surgery Upregulates High Mobility Group Box-1 and Disrupts the Blood-brain Barrier Causing Cognitive Dysfunction in Aged Rats. CNS Neurosci Ther. 2012;18(12):994-1002. PubMed PMID: 23078219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. AU - He,Hui-Juan, AU - Wang,Yi, AU - Le,Yuan, AU - Duan,Kai-Ming, AU - Yan,Xue-Bin, AU - Liao,Qin, AU - Liao,Yan, AU - Tong,Jian-Bin, AU - Terrando,Niccolò, AU - Ouyang,Wen, Y1 - 2012/10/19/ PY - 2012/08/09/received PY - 2012/09/16/revised PY - 2012/09/17/accepted PY - 2012/10/20/entrez PY - 2012/10/20/pubmed PY - 2013/5/10/medline SP - 994 EP - 1002 JF - CNS neuroscience & therapeutics JO - CNS Neurosci Ther VL - 18 IS - 12 N2 - AIM: Postoperative cognitive dysfunction (POCD) is a growing and largely underestimated problem without defined etiology. Herein, we sought to determine the relationship between cognitive decline, blood-brain barrier (BBB) permeability, and inflammation, namely high mobility group box-1 (HMGB1), after surgery in aged rats. METHODS: Aged rats were randomly assigned as surgery group (n = 45, splenectomy under general anesthesia), anesthesia (n = 45, 2% isoflurane for 2 h), and naïve control (n = 15). Markers of inflammation were measured in plasma and brain. Blood-brain barrier ultrastructure and permeability were measured by transmission electron microscope (TEM) and IgG immunohistochemistry. Cognitive function was assessed in a reversal learning version of the Morris water maze (MWM). RESULTS: Surgical trauma under general anesthesia caused distinct changes in systemic and central proinflammatory cytokines. Levels of HMGB1 and the receptor for advanced glycation end products (RAGE) were significantly upregulated in the hippocampus of operated animals. Immunohistochemistry and TEM showed BBB disruption induced by surgery and anesthesia. These molecular changes were associated with cognitive impairment in latency with the MWM up to postoperative day 3. CONCLUSIONS: 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. SN - 1755-5949 UR - https://www.unboundmedicine.com/medline/citation/23078219/Surgery_upregulates_high_mobility_group_box_1_and_disrupts_the_blood_brain_barrier_causing_cognitive_dysfunction_in_aged_rats_ L2 - https://doi.org/10.1111/cns.12018 DB - PRIME DP - Unbound Medicine ER -