Aggravation of seizure-associated microvascular injuries by ibuprofen may involve multiple pathways

Recently we reported that intrathalamic microinjection of carbachol triggers generalized convulsive seizures (GCS) followed by severe inflammatory response including edema, microhemorrhages, and subsequent degeneration of amygdaloallocortical area. Our further observations of increased expression of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β immunoreactivity (IR) confirmed the inflammatory nature of the brain damage following GCS. In the presented experiments, we addressed possible effects of a nonspecific cyclooxygenase (COX) inhibitor (ibuprofen), in the development of inflammatory response following thalamic-induced GCS.

In male Wistar rats, intrathalamic microinjection of carbachol (55 nm, 100 nl) within 2 h induced three to four episodes of GCS of an average duration of 57 s, each which led to the development of edema associated with microhemorrhages at 72 h and changes in expression of TNF-α/IL-1β IR in the amygdaloallocortical area as revealed by immunohistochemistry at 24 h.

Ibuprofen when administered intraperitoneally 30 min after the episode of GCS dramatically increased edema and microhemorrhages. It also increased expression of TNF-α/IL-1β in microvessels and decreased IL-1β IR in microglia/macrophages.

Experiments suggest that in our model, inhibition of COX pathway early after GCS may increase rather than reduce the inflammatory consequences of GCS, suggesting that COX products may have a negative feedback effect on the development of edema by modifying the expression of "proinflammatory" cytokines. There is also a possibility that ibuprofen may exert its action through other than COX-associated pathways.