Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
10
05
2019
accepted:
19
06
2019
pubmed:
30
7
2019
medline:
30
5
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
Postoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19-52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood. We utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S-adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested. PND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S-adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice. Serum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.
Sections du résumé
BACKGROUND
Postoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19-52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood.
METHODS
We utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S-adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested.
RESULTS
PND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S-adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice.
CONCLUSIONS
Serum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.
Identifiants
pubmed: 31353838
doi: 10.1002/acn3.50838
pmc: PMC6689684
doi:
Substances chimiques
Homocysteine
0LVT1QZ0BA
S-Adenosylmethionine
7LP2MPO46S
Folic Acid
935E97BOY8
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1435-1444Subventions
Organisme : NIH HHS
Pays : United States
Organisme : Elite Team Grant of the Fourth Military Medical University
Pays : International
Organisme : National Natural Science Foundation of China
ID : 8172018012
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81730032
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81771421
Pays : International
Organisme : Henry K. Beecher Professorship from Harvard University
Pays : International
Organisme : Shanghai Natural Science Foundation
ID : 16410724500
Pays : International
Informations de copyright
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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