Magnetic resonance imaging under isoflurane anesthesia alters cortical cyclooxygenase-2 expression and glial cell morphology during sepsis-associated neurological dysfunction in rats

Background:Magnetic resonance imaging(MRI)of rodents combined with histol-ogy allows to determine what mechanisms underlie functional and structural brain changes during sepsis-associated encephalopathy.However,the effects of MRI per-formed in isoflurane-anesthetized rodents on modifications of the blood-brain bar-rier and the production of vasoactive prostaglandins and glia cells,which have been proposed to mediate sepsis-associated brain dysfunction,are unknown.Methods:This study addressed the effect of MRI under isoflurane anesthesia on blood-brain barrier integrity,cyclooxygenase-2 expression,and glial cell activation during cecal ligature and puncture-induced sepsis-associated brain dysfunction in rats.Results:Cecal ligature and puncture reduced food intake and the righting reflex.MRI under isoflurane anesthesia reduced blood-brain barrier breakdown,decreased cir-cularity of white matter astrocytes,and increased neuronal cyclooxygenase-2 immu-noreactivity in the cortex 24 hours after laparotomy.In addition,it annihilated cecal ligature and puncture-induced increased circularity of white matter microglia.MRI under isoflurane anesthesia,however,did not alter sepsis-associated perivascular cyclooxygenase-2 induction.Conclusion:These findings indicate that MRI under isoflurane anesthesia of rodents can modify neurovascular and glial responses and should,therefore,be interpreted with caution.

Macrophage populations and self-renewal:Changing the paradigm

The origin of macrophages has been considered since several decades to be a continuum from bone marrow （BM） to tissue via monocytes as precursors. The development of new tools such as genetic lineage tracing,parabiosis and BM chimeras changed the paradigm of macrophage origin. In steady state, most resident macro-phages are of embryonic origin, whereas a monocyte origin remains prominent in pathological conditions. The findings of a proliferation of mature macrophages will oblige us to reappraise the relationship between proliferation and differentiation in macrophages. This review is based on the recent explosion of high impact articles on macrophage biology. It summarizes new data on the origin of macrophages and their self-renewal potential in steady states. While monocytes are required for intestinal macrophage development, the microglia is independent of monocyte influx and skin macrophages provide an excellent model of the balance between monocyte input and self-renewal. In addition, macrophage proliferation requires intrinsic and extrinsic factors including growth factors and cytokines. It also analyzes the impact of this new paradigm in human diseases such as athrosclerosis, cancer, infe-ctious diseases and neurodegenerative diseases. In atherosclerosis, the fnding of macrophage proliferation within the lesions will change our understanding of disease pathophysiology, this new paradigm may have therapeutical impact in the future.