Perpetual macrophages in hippocampus drive sepsis memory loss
Permanent macrophages that settle in the hippocampus after sepsis drive long‑term memory loss.
21 Oct 2026 0 reads Compiled with AI
#Sepsis #Macrophages #Hippocampus #Natalizumab #PTN #Microglia
Severe infections that trigger sepsis can leave survivors with lingering brain fog and memory problems months after the infection has cleared. A recent study from the Chinese Academy of Medical Sciences shows that these long‑term deficits are driven by immune cells that permanently settle in the hippocampus during the acute phase of sepsis. The study used a mouse model of sepsis to follow the fate of peripheral immune cells that cross the blood–brain barrier.
Bone‑marrow chimeras labeled with green fluorescent protein revealed that CCR2+ macrophages that enter the hippocampus within days of sepsis do not leave the brain. At three days, one month, and six months after the infection, these cells remained embedded, down‑regulated inflammatory markers, and adopted a brain‑resident phenotype. Dual‑color transplantation experiments confirmed that only the cells that arrived during the initial crisis established the long‑term population, with no new cells recruited later.
Mechanism of Long-Term Inflammation
Once established, the macrophages produce a cytokine called pleiotrophin (PTN). PTN binds to CD11b receptors on neighboring microglia, triggering genes that make the microglia over‑eat myelin sheaths that protect nerve fibers. Microscopic imaging showed that the macrophage‑laden area had microglia engulfing large amounts of myelin basic protein, a hallmark of myelin loss.
Because the harmful macrophages enter the brain only during the acute infection, the researchers tested whether blocking this entry could protect cognition. They treated mice with the drug natalizumab, which blocks alpha‑4 integrin‑mediated migration, on days 0, 3, and 6 after sepsis induction. The drug markedly reduced the number of persistent macrophages and, six months later, the mice performed normally on tests of working memory, recognition, and spatial learning.
The team also examined post‑mortem hippocampal tissue from human patients who had survived severe infections. They found a higher density of CD74+ cells that lacked the microglial marker TMEM119, clustered around blood vessels—exactly the phenotype seen in the mouse macrophages. These findings confirm that the same permanent immune infiltrate exists in humans, linking acute infection to chronic cognitive decline.