Tumor necrosis factor-alpha induced pathology in the rat brain: characterization of stereotaxic injection model

Tumor necrosis factor alpha (TNF-alpha) is a cytokine of cytotoxic and proinflammatory properties. It is believed to play an important role in inflammatory and demyelinization processes in the central nervous system (CNS). The aim of this study was to investigate what pathological changes could be produced by a stereotaxic administration of TNF-alpha in vivo into rat brain. Specimens were evaluated after staining with hematoxylin and eosin (H & E), Kluver-Barrera staining and using immunocytochemical methods. Disturbances of the blood-brain barrier (BBB) were analyzed as well as inflammatory infiltrates, changes in neurons, astrocytes and myelin. TNF-alpha injected in vivo into a rat brain caused a prominent inflammatory reaction in the cerebral meninges and a local cytotoxic brain edema when compared with the control group. Moreover, disturbances of the BBB premeability, infiltration of blood-borne macrophages in the area of the cytokine injection and early arising astrogliosis were observed. These results suggest that TNF-alpha can be an important mediator of inflammatory processes in the CNS.