Central Nervous System Inflammation and Prion Disease Pathogenesis

The study of inflammation in the prion diseases is relatively new. Indeed, for a number of years the accepted dogma was that the prion diseases lacked an inflammatory response in the brain (1–3). This persists in spite of a number of studies showing that the pathological hallmarks of the prion diseases (PrPSc deposition, astrocytosis, vacuolation, and neuronal loss) are associated with the presence of activated microglia (4–7). At the heart of this discrepancy is a simple matter of what is meant by inflammation. The innate inflammatory response is the tissue’s response to injury or infection, and, as so succinctly put by Metchnikoff in the late ninetenth century, “The essential and primary element in typical inflammation consists in a reaction of the phagocytes against a harmful agent” (8). Given that the microglia are the brain’s resident macrophages (i.e., phagocytic cells), we believe that the presence of activated microglia in prion-affected brains represents an inflammatory response (9–11).