Role Of Inflammation And Glutamate

Although expression of cytokines and their contribution to neural injury and inflammatory responses are well characterized in instances of cerebral ischemia and head injury, ICH was not associated with expression of TNF-a, IL-1P, or IL-6, either in the perihematoma region or in other regions of the brain, when blood and cerebrospinal fluid (CSF) were tested 1 hr after the onset of hemorrhage (74). The increase of inflammatory markers only becomes measurable in situations in which the BBB is permeable (75 ).

Data also supports the probability that the migration of leukocytes and platelets into the perihematoma region, along with the release of vasoactive factors, contributes to secondary injury in ICH. In the animal model, the systemic depletion of platelets and lymphocytes through irradiation can reduce edema formation in the perihematoma region, which suggests a role for circulating leukocytes and platelets in the pathogenesis of edema (75).

The delay in the breakdown of the BBB and development of cerebral edema after ICH strongly suggest the existence of secondary mediators (e.g., glutamate) of both edema and neuronal injury. The neurotoxicity of glutamate and other excitatory amino acids is the result of excessive activation of postsynaptic N-methyl-D-aspartate (NMDA) receptors (76). This activation of NMDA receptors leads to a cellular influx of calcium ions, concurrently activating a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors and facilitating the incorporation of sodium ions into the cells. Intracellular accumulations of calcium and sodium ions give rise to edema and neuronal death (77). In experimental ICH, glutamate and other excitatory amino acids have also been found to accumulate early and transiently in extracellular fluids in the perihematoma region. The role of these amino acids in the pathogenesis of neuronal injury observed in ICH is unclear. Likewise, it is unclear whether this increase in extracellular concentration of amino acids is related to compression of tissue that can be reproduced by intraparenchymal balloon inflation or whether some chemical component is involved that can only be generated by blood and its constituents (78 ).

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