Protease activated receptor-1 and brain edema formation in glioma models.

OBJECTIVE

Our previous studies showed that thrombin contributes to brain edema in gliomas. The present study investigated the role of a thrombin receptor, protease activated receptor-1 (PAR-1), in edema formation in glioma models.

METHODS

These experiments were performed in Fischer 344 rats, PAR-1 knockout mice, and wild-type C57BL/6 mice controls. F98 glioma cells were infused into the right caudate. Animals were euthanized and the brains were used for measurements of brain edema and PAR-1 expression.

RESULTS

In rats, implantation of glioma cells resulted in significant brain edema in the ipsilateral hemisphere (82.6 ± ;1.4 vs. 78.1 ± 0.9 % in the contralateral hemisphere, p < 0.01). By Western blot analysis and RT-PCR, we found that both protein and mRNA levels of PAR-1 were upregulated in the glioma (p < 0.01). In mice, implantation of glioma cells also caused brain edema in the ipsilateral hemisphere (p < 0.05). Glioma-induced brain edema was less in PAR-1 knockout mice (day 12: 79.4 ;± 1.3 vs. 81.5 ± 1.1 % in the wild-type mice, p < ;0.05).

CONCLUSIONS

PAR-1 plays a role in glioma-induced brain edema. Clarification of the role of PAR-1 in edema formation should help to develop new therapeutic strategies for gliomas.