A marked increase of perivascular SP staining compared to controls was observed from 2 weeks following tumor cell inoculation and persisted until the final time point of 4 weeks. Due to the significant increase in BBB disruption as observed with albumin quantification, the 3 week time point was chosen for the quantification of SP and the NK1 receptor using the color deconvolution method. This confirmed the qualitative assessment, revealing a significant increase in perivascular SP staining in tumor inoculated animals compared to controls at 3 weeks. Similarly, an obvious increase in NK1 receptor staining was observed in the area surrounding the tumor such that it was apparent using low power magnification. This was particularly evident at the 3 weeks time point, and quantified using color deconvolution. Indeed, a significant increase in overall NK1 receptor staining was evident at 3 weeks, as well as a significant increase in NK1 receptor content in the tumor-inoculated hemisphere when compared to the contralateral hemisphere of the same animal. Only a moderate increase in perivascular NK1 receptor staining was evident at both 2 and 3 weeks following tumor cell injection, however by 4 weeks a marked increase in perivascular NK1 receptor immunoreactivity was observed. Given that marked BBB disruption evident at 3 weeks as assessed by albumin staining, as well as corresponding significant increases in SP and NK1 receptor immunoreactivity, this time point was accordingly selected for intervention with the NK1 antagonist Emend. Following tumor cell inoculation, a significant increase in both BBB permeability and brain water content occurred compared to shams. In contrast, brain water content within the right hemisphere in vehicle treated groups remained significantly increased compared to control animals. Tumor-associated edema is one of the primary causes of CNS symptoms in brain tumor patients, with clinical deficits more often caused by edema than by the mass effect of the tumor itself.