Immunocompromised mice are routinely used in cancer research, as the immune deficient nature of this strain allows for examination of human cancer cells in an animal model. However, one limitation of the use of these animals is the translational potential of research carried out in immune deficient species. Nonetheless, the results of the present study using immunocompromised mice are consistent with previous studies performed in immune competent animals, suggesting a dominant role for SP and the NK1 receptor in neurogenic inflammation in a variety of models of CNS BAY 73-6691 disease. Furthermore, the pattern of SP immunoreactivity, as well as the observed decreases in BBB permeability and brain water content are consistent among these studies, highlighting the reproducibility of these results in both immune-competent and deficient species, and thus the translational potential of SP antagonists as a therapy for cerebral edema. In the present study, both SP and the NK1 receptor were increased in the entire tumor-inoculated hemisphere when compared to the contralateral side, indicating a possible role for SP in mediating the process of edema formation within the peritumoral region. Indeed, NK1 receptor staining was so significantly increased in the peritumoral region such that it was visible at low power. This correlated with the observed area of albumin staining, implicating SP and in the genesis of BBB breakdown and the development of cerebral edema. It was noted that the increase in both albumin and NK1 receptor staining was most pronounced at 3 weeks, and thus was chosen for quantitation. However, this peak may be more a reflection of model mortality given that a number of animals had to be euthanased due to tumor burden before the 4-week time point. Additionally, a marked increase in SP staining was observed in the vasculature surrounding the tumor at all time points, further supporting this proposed role. The precise molecular mechanisms by which the NK1 receptor and SP are upregulated in the 5-AIQ hydrochloride setting of brain tumor edema have yet to be fully elucidated. The link between inflammation and cancer has been well established, with many chronic inflammatory states associated with cancer development, as inflammation increases both mitogenesis and mutagenesis. Similarly, it is well known that both SP and the NK1 receptor are increased in inflammatory conditions, with increased expression of SP and NK1 receptor mRNA reported in response to inflammation.