The human brain after surgery - trauma-induced neuroinflammation, neurocognitive decline and dementia
Description: This translational project explores mechanisms and pathophysiology, prevention and outcomes related to long-term neurocognitive decline and risk for dementia after major surgery. The ultimate goal is to provide novel prognostic and therapeutic strategies and patient-centered guidelines for safer perioperative care. We hypothesize that adverse immune response signatures to surgical trauma with impaired periphery-to-brain communication leads to unresolved systemic and neuroinflammation with risk for neurocognitive decline and dementia. Using comprehensive clinical and experimental platforms in man, animals and cells, we will in standardized surgical cohorts in Part A define a longitudinal in-depth immunological, transcriptional, and soluble atlas with a periphery-to-brain axis coupled to hard adverse brain outcomes related to neuroinflammation, neurodegeneration and risk for dementia. Key findings from this effort will in Part B be mechanistically explored in established animal models and in vitro systems to provide in-depth knowledge on targets for prognostic and possibly therapeutic strategies. Information from preclinical and clinical investigations (Part A-B) on precision-based immune signatures will be prospectively validated in broader surgical populations to search at-risk patients (part C). This knowledge will ultimately serve as base for novel perioperative guidelines and therapeutic strategies to prevent neurocognitive decline or dementia after surgery.
Funder: Vetenskapsrådet
Amount: SEK 7,200,000
Funding type: research
Funder scheme: Project grant
Start date: 2023-12-01
End date: 2027-11-30
Investigator: Lars I Eriksson
Institution: Karolinska Institutet
Funded outputs count: 0
Funder award ID: 2023-02000
OpenAlex ID: G6007876484