Focal brain lesions can lead to metabolic and structural changes in areas distant from but connected to the lesion site. After focal ischemic or excitotoxic lesions of the cortex and/or striatum, secondary changes have been observed in the thalamus, substantia nigra pars reticulata, hippocampus and spinal cord. In all these regions, inflammatory changes characterized by activation of microglia and astrocytes appear. In the thalamus, substantia nigra pars reticulata and hippocampus, an expression of proinflammatory cytokine like tumor necrosis factor-alpha and interleukin-1beta is induced. However, time course of expression and cellular localisation differ between these regions. Neuronal damage has consistently been observed in the thalamus, substantia nigra and spinal cord. It can be present in the hippocampus depending on the procedure of induction of focal cerebral ischemia. This secondary neuronal damage has been linked to antero- and retrograde degeneration. Anterograde degeneration is associated with somewhat later expression of cytokines, which is localised in neurons. In case of retrograde degeneration, the expression of cytokines is earlier and is localised in astrocytes. Pharmacological intervention aiming at reducing expression of tumor necrosis factor-alpha leads to reduction of secondary neuronal damage. These first results suggest that the inflammatory changes in remote areas might be involved in the pathogenesis of secondary neuronal damage.