Pre-treatment with nimodipine and 7.5% hypertonic saline protects aged rats against postoperative cognitive dysfunction via inhibiting hippocampal neuronal apoptosis.

Abstract

OBJECTIVE:

This study aimed to investigate the effects of pre-treatment with nimodipine and 7.5% hypertonic saline (HS) on postoperative cognitive dysfunction (POCD) in aged rats.

METHODS:

Healthy Sprague-Dawley aged rats were randomly assigned into 4 groups: POCD group, nimodipine group, HS group, and nimodipine+HS group. Rats in POCD group received normal saline injection and then splenectomy 30min later under 1.8% isoflurane inhalation for 2h. In remaining groups, rats received injection of 1mg/kg nimodipine (i.p) and/or 4ml/kg 7.5% HS (i.v) and then splenectomy. Morris water maze test was performed before and after surgery. The hippocampus was harvested for the detection of neuronal apoptosis rate (AR), cytoplasmic calcium ([Ca2+]i), Bcl-2 and Bax mRNA expression and hippocampal neuronal ultrastructure.

RESULTS:

When compared with POCD group, the latency to escape, neuronal AR, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced dramatically, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly (P<0.05) in nimodipine group, NS group and nimodipine+HS group. In addition, the latency to escape, neuronal AR, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced markedly, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly in nimodipine+HS group as compared to nimodipine group and NS group (P<0.05). Hippocampal neuronal ultrastructure damage was observed in all 4 groups, but it was the mildest in nimodipine+HS group.

CONCLUSION:

Pre-treatment with both nimodipine and 7.5% HS exerts better protective effects, which is related to the inhibition of hippocampal neuronal apoptosis.

• Authors: Zhang Qi, Yuan Tianbao, Li Yanan, Xin Xi, He Jinhua, Wang Qiujun
• Journal: Behavioural brain research (Behav Brain Res) Vol. 321 Pg. 1-7 (03 15 2017) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 28017853 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Bax protein, rat
• Bcl2 protein, rat
• Neuroprotective Agents
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Saline Solution, Hypertonic
• bcl-2-Associated X Protein
• Nimodipine

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Cognition Disorders (etiology, pathology, physiopathology, prevention & control)
• Disease Models, Animal
• Drug Therapy, Combination
• Hippocampus (drug effects, pathology, physiopathology)
• Male
• Maze Learning (drug effects, physiology)
• Neurons (drug effects, pathology, physiology)
• Neuroprotective Agents (pharmacology)
• Nimodipine (pharmacology)
• Postoperative Complications (pathology, physiopathology, prevention & control)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• RNA, Messenger (metabolism)
• Random Allocation
• Rats, Sprague-Dawley
• Saline Solution, Hypertonic (pharmacology)
• Splenectomy
• Time Factors
• bcl-2-Associated X Protein (metabolism)