CELLULAR INFLAMMATORY RESPONSE AFTER SPINAL-CORD INJURY IN SPRAGUE-DAWLEY AND LEWIS RATS

The distribution of microglia, macrophages, T-lymphocytes, and astrocy tes was characterized throughout a spinal contusion lesion in Sprague- Dawley and Lewis rats by using immunohistochemistry. The morphology, s patial localization, and activation state of these inflammatory cells were described both qualitatively and quantitatively at 12 hours, 3, 7 , 14, and 28 days after injury. By use of OX42 and ED1 antibodies, pea k microglial activation was observed within the lesion epicenter of bo th rat strains between three and seven days post-injury preceding the bulk of monocyte influx and macrophage activation (seven days). Rostra l and caudal to the injury site, microglial activation plateaued betwe en two and four weeks post-injury in the dorsal and lateral funiculi a s indicated by morphological transformation and the de-novo expression of major histocompatibility class II (MHC II) molecules. Similar to t he timing of microglial reactions, T-lymphocytes maximally infiltrated the lesion epicenter between three and seven days post-injury. Reacti ve astrocytes, while present in the acute lesion, were more prominent at later survival times (7-28 days). These cells were interspersed wit h activated microglia but appeared to surround and enclose tissue site s occupied by reactive microglia and phagocytic macrophages. Thus, tra uma-induced central nervous system (CNS) inflammation, regardless of s train, occurs rapidly at the site of injury and involves the activatio n of resident and recruited immune cells. In regions rostral or caudal to the epicenter, prolonged activation of inflammatory cells occurs p referentially in white matter and primarily consists of activated micr oglia and astrocytes. Differences were observed in the magnitude and d uration of macrophage activation between Sprague-Dawley (SD) and Lewis (LEW) rats throughout the lesion. Increased expression of complement type 3 receptors (OX42) and macrophage-activation antigens (ED1) persi sted for longer times in LEW rats while expression of MHC class II mol ecules was attenuated in LEW compared to SD rats at all times examined . Variations in the onset and duration of T-lymphocyte infiltration al so were observed between strains with twice as many T-cells present in the lesion epicenter of Lewis rats by 3 days post-injury. These strai n-specific findings potentially represent differences in corticosteroi d regulation of immunity and may help predict a range of functional ne urologic consequences affected by neuroimmune interactions. J. Comp. N eurol. 377:443-464, 1997. (C) 1997 Wiley-Liss, Inc.