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A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Disruption of hippocampal mitochondrial function underlies opioid-induced postoperative cognitive dysfunction in aged
Stephanie M Muscat1, Nicholas P Deems2, Bryan D Alvarez2
1Institute of Brain, Behavior, and Immunology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
Brain, Behavior, and Immunity
|August 3, 2026
Summary
Surgery and morphine cause long-term memory loss in aging rats by damaging brain cell connections and mitochondria. Targeting mitochondrial health may treat postoperative cognitive dysfunction (POCD).
Area of Science:
- Neuroscience
- Gerontology
- Pharmacology
Background:
- Postoperative cognitive dysfunction (POCD) is a persistent complication in aging patients after surgery, often linked to opioid use.
- The mechanisms by which opioids contribute to long-term cognitive impairment are not fully understood.
Purpose of the Study:
- To investigate synaptic, axonal, and mitochondrial abnormalities contributing to persistent memory deficits after surgery and morphine in aged rats.
- To evaluate therapeutic strategies targeting neuroinflammation and mitochondrial dysfunction for POCD.
Main Methods:
- Utilized an aged rat model of surgery with perioperative morphine administration.
- Assessed synaptic stability, long-term potentiation, AMPA receptor function, neurofilament light chain (Nf-L) levels, and hippocampal mitochondrial function (oxidative phosphorylation, respiratory capacity, DNA oxidation).
- Investigated the effects of TLR4 inhibition and SS-31 mitochondrial rejuvenation.
Main Results:
- Surgery and morphine induced memory deficits, reduced dendritic spine subtypes, impaired long-term potentiation, and blunted GluA1 upregulation.
- Elevated Nf-L indicated sustained axonal damage; hippocampal mitochondria showed impaired function and increased DNA oxidation, distinct from liver mitochondria.
- TLR4 inhibition reduced oxidative stress and improved mitochondrial function; SS-31 treatment rescued memory deficits and normalized mitochondrial respiration.
Conclusions:
- Sustained hippocampal mitochondrial dysfunction is a key factor in long-term cognitive deficits following surgery and morphine in aged rats.
- Mitochondrial bioenergetics represents a promising therapeutic target for preventing and treating POCD.
