Tao Zhang1,
Jusheng Wu2
1Department of Anesthesiology, Jingling Hospital, Nanjing 210002, Jiangsu Province, China;
2Department of Anesthesiology, Zhuji People's Hospital, Zhuji 311800, Zhejiang Province, China.
For correspondence:- Jusheng Wu
Email: wujusheng123123@126.com
Accepted: 4 March 2022
Published: 31 March 2022
Citation:
Zhang T, Wu J.
Mechanism of propofol-induced injury in hippocampal neurons in neonatal rats. Trop J Pharm Res 2022; 21(3):605-610
doi:
10.4314/tjpr.v21i3.21
© 2022 The authors.
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Abstract
Purpose: To determine the deleterious effect of propofol on hippocampal neurons in developing rats, and the underlying mechanism.
Methods: Sixty Wistar rats were randomly assigned to fat emulsion group, low-dose propofol group and high-dose propofol group. Immunohistochemical staining of brain samples was used to detect BrdU-positive (+), nestin+ and GFAP+ cells. The influence of propofol on cellular multiplication, number of neurons in dentate gyrus, activation of astrocytes and microglial activation were determined. The expression levels of Sox2, Akt and ERK signal pathway-associated proteins were assayed by Western blotting.
Results: The population of BrdU-positive cells was significantly lower in propofol-exposed rats than in fat emulsion rats, while the levels of Sox2 protein were markedly and dose-dependably lower in propofol-exposed rats than the corresponding levels in fat emulsion rats (p < 0.05). The numbers of nestin+ cells, GFAP+ cells and Iba1+ cells in propofol-exposed rats were significantly and concentration-dependently reduced, relative to the corresponding numbers in fat emulsion rats, while p-Akt and p-ERK1/2 in propofol-exposed rats were and dose-dependently reduced, relative to fat emulsion rats (p < 0.05).
Conclusion: Propofol dose-dependently inhibits the proliferation of hippocampal dentate gyrus stem cells, and suppresses the activation of astrocytes and microglia through regulation of the expressions of Akt/ERK signal pathway-associated proteins. This provides a lead for research and development of new drugs for protecting hippocampal neurons.
Keywords: Propofol, Hippocampal neurons, Fat emulsion, Akt/ERK signal pathway, Astrocytes, Microglia, Dentate gyrus stem cell