Daily Anesthesiology Research Analysis
Three studies advance perioperative anesthesiology: a mechanistic Annals of Surgery paper identifies Kupffer cell CRIg-dependent capture of transplanted mitochondria as a liver-protective pathway in ischemia/reperfusion, a BJA mouse study implicates reduced postsynaptic BDNF in hippocampal STM-to-LTM transformation failure after surgery/anesthesia, and a BJA clinical paper links chronic postsurgical inguinal pain with dorsal root ganglion atrophy and serum biomarkers. Together, they point to org
Summary
Three studies advance perioperative anesthesiology: a mechanistic Annals of Surgery paper identifies Kupffer cell CRIg-dependent capture of transplanted mitochondria as a liver-protective pathway in ischemia/reperfusion, a BJA mouse study implicates reduced postsynaptic BDNF in hippocampal STM-to-LTM transformation failure after surgery/anesthesia, and a BJA clinical paper links chronic postsurgical inguinal pain with dorsal root ganglion atrophy and serum biomarkers. Together, they point to organ protection strategies, neurocognitive mechanisms, and biomarker-guided pain diagnosis.
Research Themes
- Kupffer cell–mediated mitochondrial transplantation for liver I/R protection
- BDNF-dependent memory consolidation deficits after surgery/anesthesia
- Biomarkers and imaging signatures for chronic postsurgical pain
Selected Articles
1. Mitochondrial Transplantation: A Novel Therapy for Liver Ischemia/Reperfusion Injury.
In mouse liver I/R, exogenous mitochondrial transplantation reduced hepatocellular injury, inflammatory cytokines, and neutrophil infiltration. Intravital imaging showed rapid Kupffer cell sequestration and lysosomal acidification of transplanted mitochondria, and CRIg on Kupffer cells was required for capture and protection.
Impact: This study provides a mechanistic basis for mitochondrial transplantation as an organ-protective therapy in perioperative liver I/R, identifying CRIg-dependent Kupffer cell capture as necessary for benefit.
Clinical Implications: Suggests a translatable strategy to mitigate liver I/R injury in hemorrhagic shock, major liver surgery, and transplantation, and nominates CRIg–Kupffer cell interactions as a target to enhance efficacy or select candidates.
Key Findings
- Mitochondrial transplantation reduced ALT/AST elevations and histologic injury after liver I/R.
- Pro-inflammatory cytokines (IL-6, TNFα) decreased while IL-10 increased following MTx.
- Neutrophil infiltration in liver sinusoids and lung BAL fluid was reduced, indicating local and distant anti-inflammatory effects.
- Intravital imaging showed Kupffer cells rapidly sequester and acidify transplanted mitochondria.
- Kupffer cell depletion abrogated protection, and CRIg knockout prevented mitochondrial capture and hepatoprotection.
Methodological Strengths
- Rigorous mechanistic in vivo design with intravital imaging and transgenic/knockout models
- Cell-type specific depletion (Clec4f/iDTR) to establish necessity of Kupffer cells and CRIg pathway
Limitations
- Preclinical murine model limits direct generalizability to humans
- Dose, timing, and source of mitochondria require optimization for clinical translation
Future Directions: Early-phase clinical trials to evaluate safety/feasibility of MTx in liver surgery/transplant, and strategies to augment CRIg-mediated capture or target delivery.
OBJECTIVE: To investigate the hepatoprotective effects of mitochondrial transplantation (MTx) in a murine liver ischemia/reperfusion (I/R) model. BACKGROUND: Sequential liver ischemia, followed by reperfusion (I/R), is a pathophysiological process underlying hepatocellular injury in a number of clinical contexts, such as hemorrhagic shock/resuscitation, major elective liver surgery, and organ transplantation. A unifying pathogenic consequence of I/R is mitochondrial dysfunction. Restoration of mitochondria through transplantation (MTx) has emerged as a potential therapeutic in I/R. However, its role in liver I/R and its mechanisms of action remain poorly defined. METHODS: We investigated the hepatoprotective effects of MTx in an in vivo mouse model of liver I/R and used in vivo imaging and various knockout and transgenic mouse models to determine the mechanism of protection. RESULTS: We found that I/R-induced hepatocellular injury was prevented by MTx, as measured by plas
2. Role of brain-derived neurotrophic factor in dysfunction of short-term to long-term memory transformation after surgery and anaesthesia in older mice.
Surgery/anesthesia in older mice impaired STM-to-LTM transformation alongside reduced CA1 Vglut1+ neuron activity and postsynaptic BDNF. Restoring BDNF specifically in Vglut1+ neurons rescued both synaptic plasticity (E-LTP to L-LTP) and memory transformation.
Impact: Identifies a cell-type specific BDNF deficit as a mechanistic driver of postoperative neurocognitive dysfunction, pointing to a rational therapeutic target.
Clinical Implications: Supports exploration of BDNF-enhancing or TrkB-targeted interventions, and strategies to preserve hippocampal glutamatergic synaptic function in older surgical patients.
Key Findings
- Surgery/anesthesia impaired STM→LTM and E-LTP→L-LTP transformations in older mice.
- Activity of CA1 Vglut1+ glutamatergic neurons and postsynaptic BDNF levels decreased after surgery/anesthesia.
- Cell-type specific BDNF overexpression in Vglut1+ neurons restored memory transformation and synaptic plasticity.
Methodological Strengths
- Use of optogenetics/chemogenetics to establish cell-type specific causality
- Multimodal assessment (synaptosome BDNF, Golgi-Cox, electrophysiology) corroborating findings
Limitations
- Findings are preclinical in mice and may not directly translate to humans
- Specific anesthetic/surgical paradigms may influence generalizability
Future Directions: Test BDNF/TrkB-targeted and synaptic plasticity–modulating interventions in aged models and pilot perioperative trials; evaluate biomarkers of hippocampal BDNF signaling.
BACKGROUND: Memory decline is one of the main manifestations in perioperative neurocognitive disorder. Short-term memory (STM) to long-term memory (LTM) transformation is one aspect of memory consolidation. Early-phase long-term potentiation (E-LTP) to late-phase long-term potentiation (L-LTP) is the molecular correlate of STM to LTM transformation. We examined whether the STM to LTM transformation was impaired after anaesthesia and surgery in older mice. METHODS: Optogenetics and chemogenetics were used to confirm the role of Vglut1+ glutamatergic neurones in the STM to LTM transformation in older mice. Synaptosomes were isolated to analyse expression of brain-derived neurotrophic factor (BDNF). Golgi-Cox staining and hippocampal field potential recordings were also used to measure synaptic plasticity. RESULTS: We found that the STM to LTM and E-LTP to L-LTP transformations were impaired after anaesthesia and surgery in older mice, and Vglut1+ excitatory neurone activity in the hippocampal CA1 region was reduced. BDNF expression decreased in the postsynaptic fraction, especially in Vglut1+ neurones, whereas cell-type specific overexpression of BDNF in Vglut1+ neurones reversed postoperative STM to LTM transformation dysfunction in older mice. CONCLUSIONS: Reduced BDNF expression was involved in anaesthesia and surgery-induced impairment of the STM to LTM transition involving glutamatergic neurones in the hippocampal CA1 region of older mice. This provides a potential target that might be helpful for understanding and developing treatments for postoperative neurocognitive dysfunction.
3. Chronic postsurgical inguinal pain: incidence and diagnostic biomarkers from a large German national claims database.
In a national claims cohort, new chronic inguinal pain after hernia surgery was common. Deep phenotyping revealed unilateral L1 DRG atrophy and a biomarker signature (↑BDNF, ↑CCL2, ↓ApoA1) plus anxiety correlating with CPIP, suggesting an objective diagnostic framework.
Impact: Combines real-world incidence with multi-modal biomarker and imaging correlates, advancing objective diagnosis of CPIP.
Clinical Implications: Supports incorporating DRG MRI and serum markers (BDNF, CCL2, ApoA1) with anxiety screening to stratify CPIP patients and tailor therapy.
Key Findings
- Among 11,221 hernia surgeries, a similar proportion of patients with pre-existing pain improved while a comparable percentage developed new chronic inguinal pain.
- CPIP patients exhibited unilateral L1 DRG atrophy; those with de novo pain had −24% ipsilateral vs contralateral DRG volume.
- Serum BDNF and CCL2 were elevated and ApoA1 reduced; the cluster of DRG atrophy, BDNF, ApoA1, and anxiety best correlated with CPIP diagnosis.
Methodological Strengths
- Large national claims dataset with one-year follow-up for incidence estimation
- Deep phenotyping with sensory testing, serum proteomics, and DRG MRI in well-characterized cases/controls
Limitations
- Deep phenotyping sample size for CPIP cases was small (n=17), limiting precision
- Observational design susceptible to selection and confounding biases
Future Directions: Prospective validation of biomarker–imaging panels, integration into diagnostic algorithms, and trials testing mechanism-informed interventions.
BACKGROUND: Chronic postsurgical inguinal pain (CPIP) is the most common complication of groin hernia surgery. The characteristics of patients, their medical care, and choice of diagnostic tools remain to be defined to optimise preventive and therapeutic interventions. METHODS: Claims data from 2018 and a 1-yr follow-up were analysed for incidence and medical care. A separate cohort (141 healthy controls and 17 CPIP patients) was examined by deep phenotyping. This included sensory testing, blood and skin biopsies, MRI of the dorsal root ganglion (DRG), and patient-reported outcomes. RESULTS: Of 11,221 patients with hernia surgery in 2018 identified, 8.5% had pain before that was relieved by surgery, but a similar percentage had novel pain in this region. Deep phenotyping of 141 healthy controls provided a map of the inguinal sensory system. The following analysis of patients with CPIP revealed that they suffered from moderate pain with neuropathic features, individual sensory abnormalities, and unilateral L1 DRG atrophy. In the blood, levels of C-C-motif chemokine ligand (CCL2) and brain-derived neurotrophic factor (BDNF) were upregulated, whereas apolipoprotein A1 (ApoA1) concentration was reduced. A cluster of DRG atrophy, BDNF, ApoA1, and anxiety correlated best with the diagnosis. CPIP patients with novel pain had significantly more DRG atrophy (-24% ipsilateral vs contralateral volume). CONCLUSIONS: CPIP is often newly acquired after surgery. A combination of DRG imaging, serum markers, and anxiety screening can support the diagnosis. In the future, this could guide clinicians towards more personalised therapies (e.g. targeting anxiety or lipid profiles) and possible altered surgical techniques. CLINICAL TRIAL REGISTRATION: German Trial Registry DRKS00024588 and DRKS00016790.