Cytokine-induced acute inflammation in the brain and spinal cord

Different compartments in the central nervous system mount distinct inflamm atory responses. The meninges and choroid plexus respond to pro-inflammator y stimuli in a manner reminiscent of a peripheral inflammatory response, wh ereas the brain parenchyma is refractory. Trauma-induced lesions in brain a nd in spinal cord are associated with leukocyte infiltration, blood-brain b arrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, the se phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these diff erences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotacticall y injected recombinant rat (rr) TNF alpha or rrIL-1 beta into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNF alp ha failed to evoke BBB breakdown or leukocyte recruitment, whereas in the s pinal cord injection of TNF alpha resulted in marked BBB breakdown and leuk ocyte recruitment. Similarly, the injection of rrIL-1 beta into the brain p arenchyma failed to induce BBB breakdown and gave rise to only minimal neut rophil recruitment, whereas the injection of rrIL-1 beta into the spinal co rd induced significant BBB breakdown and recruitment of neutrophils and lym phocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in t he inflammatory response between the brain parenchyma and spinal cord paren chyma. This observation has important implications for the treatment of spi nal cord injuries.