Long-Term Effects of Isoflurane Anesthesia and Surgery: Sex-Associated Neurological Dysfunction and Alterations in Circulating Extracellular Vesicles
- 1Department of Anesthesiology and Shock, Trauma and Anesthesiology Research Center (STAR), University of Maryland School of Medicine, Baltimore, MD 21201, USA
- 2Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- 3University of Maryland- Medicine Institute for Neuroscience Discovery (UM-MIND), University of Maryland School of Medicine, Baltimore, MD 21201, USA
Abstract
Volatile anesthetics and surgery can trigger neuroinflammation and neurological dysfunction, but their long-term effects remain poorly understood. Young adult male and female C57BL/6 mice underwent 4 h of 2% isoflurane anesthesia combined with laparotomy (Iso/OP) or sham treatment. At 12 weeks, olfactory and cognitive functions were assessed, followed by RNA sequencing of olfactory bulbs and hippocampi and plasma extracellular vesicle (EV) profiling. EV-associated inflammatory bioactivity was evaluated by hippocampal injection into naïve male mice. Iso/OP induced olfactory deficits at 12 weeks, with greater impairment in females. Female mice also exhibited deficits in spatial working memory and associative learning, whereas males showed relatively preserved cognitive function. Transcriptomic analyses revealed sex-dependent alterations in pathways related to synaptic function, neurodevelopment, extracellular matrix remodeling, stress responses, and chemotaxis. Iso/OP reduced circulating EV abundance, particularly among 40–100 nm particles, and altered EV proteomic profiles. Exploratory analyses of pooled hippocampal tissues revealed distinct cytokine and chemokine profiles following injection of plasma EVs from the four donor groups. Collectively, these findings demonstrate sex-dependent neurological and molecular alterations persisting 12 weeks after Iso/OP, accompanied by changes in circulating EVs. The exploratory EV transfer findings warrant further investigation into the potential contribution of circulating EVs to brain inflammatory responses.
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BibTeX
@article{li2026longterm,
title = {{Long-Term Effects of Isoflurane Anesthesia and Surgery: Sex-Associated Neurological Dysfunction and Alterations in Circulating Extracellular Vesicles}},
author = {Yun Li and Ruth Park and Balaji Krishnamachary and Hangnoh Lee and Zhuofan Lei and Hui Li and Junfang Wu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219936},
url = {https://www.mdpi.com/1422-0067/27/21/9936},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-Term Effects of Isoflurane Anesthesia and Surgery: Sex-Associated Neurological Dysfunction and Alterations in Circulating Extracellular Vesicles
AU - Yun Li
AU - Ruth Park
AU - Balaji Krishnamachary
AU - Hangnoh Lee
AU - Zhuofan Lei
AU - Hui Li
AU - Junfang Wu
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219936
UR - https://www.mdpi.com/1422-0067/27/21/9936
AB - Volatile anesthetics and surgery can trigger neuroinflammation and neurological dysfunction, but their long-term effects remain poorly understood. Young adult male and female C57BL/6 mice underwent 4 h of 2% isoflurane anesthesia combined with laparotomy (Iso/OP) or sham treatment. At 12 weeks, olfactory and cognitive functions were assessed, followed by RNA sequencing of olfactory bulbs and hippocampi and plasma extracellular vesicle (EV) profiling. EV-associated inflammatory bioactivity was evaluated by hippocampal injection into naïve male mice. Iso/OP induced olfactory deficits at 12 weeks, with greater impairment in females. Female mice also exhibited deficits in spatial working memory and associative learning, whereas males showed relatively preserved cognitive function. Transcriptomic analyses revealed sex-dependent alterations in pathways related to synaptic function, neurodevelopment, extracellular matrix remodeling, stress responses, and chemotaxis. Iso/OP reduced circulating EV abundance, particularly among 40–100 nm particles, and altered EV proteomic profiles. Exploratory analyses of pooled hippocampal tissues revealed distinct cytokine and chemokine profiles following injection of plasma EVs from the four donor groups. Collectively, these findings demonstrate sex-dependent neurological and molecular alterations persisting 12 weeks after Iso/OP, accompanied by changes in circulating EVs. The exploratory EV transfer findings warrant further investigation into the potential contribution of circulating EVs to brain inflammatory responses.
SN - 1422-0067
ER -