Effects of glucocorticoid and chemotherapy on the peritumoral edema and astrocytic reaction in experimental brain tumor

Abstract

To study the effects of glucocorticoids and chemotherapeutic agents on the pathophysiology of the tumor-induced brain edema, the site of Evans blue-albumin extravasation, the distribution of extravasated serum albumin, and the extent of local astrocytic reaction were examined in a rat model of implanted brain tumor. Experimental brain tumors were produced by implanting small pellets of Walker 256 carcinosarcoma into the cerebral cortex of Wistar rats. In the steroid group, rats were administered with intraperitoneal methylprednisolone succinate (15 mg/kg) daily on and after the 6th day postimplantation, and sacrificed on the 14th day. In the chemotherapy group, rats were given an intravenous injection of cyclophosphamide (30 mg/kg) on the 14th day, and sacrificed on the 21st day. Rats in the untreated group were sacrificed on the 14th day without any therapy. Each animal was sacrificed by the transcardiac perfusion with paraformaldehyde 30 min after intravenous injection of Evans blue. Firstly, coronal blocks of the brain were examined for Evans blue staining macroscopically. Paraffin embedded sections were studied for the Evans blue fluorescence and for the immunohistochemical reaction to serum albumin and GFAP. The examination of Evans blue demonstrated that the origin of extravasation of serum albumin was the tumor and the adjacent brain with dense tumor cell infiltration in any group of rats. The extravasated serum albumin distributed widely and the astrocytic reaction was prominent in the brain of the untreated group. A positive correlation was observed between the intensity of albumin immunoreaction and the degree of astrocytic proliferation. Chemotherapy effectively decreased the size of tumor and reduced the extravasation of serum albumin. The astrocytic reaction was however, not reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Early blood-brain barrier disruption after high-dose single-fraction irradiation in rats

“…Previous studies with various exogenous tracers have failed to show any change in BBB permeability [3,5,13,14,18]. No leakage of trypan blue was detected in the monkey brain, even after an irradiation with 60 Gy [5].…”

“…Although increased BBB permeability soon after irradiation has not been documented by previous reports [3,5,13,14,18], an electron microscopic study has demonstrated ultrastructural evidence for increased BBB permeability [4]. As early as 6 hours after irradiation with 27 Gy, pinocytotic vesicles were increased in number in the vascular endothelium of monkey brain.…”

“…Quantitative study with 14C-urea did not detect any change after irradiation with 20 to 25 Gy in young adult rats [14]. Positron emission tomography with ~2Rb demonstrated no permeability changes in brains of beagle dogs until 20 to 29 weeks after exposure to 13 to 15 Gy [3].…”

“…Early effects of irradiation, especially on the permeability of BBB, have seldom been demonstrated. Previous investigators have used exogenous tracers to evaluate changes in BBB permeability and failed to demonstrate any significant alterations [3,5,13,14,18]. In the present study we examined the extravasation of endogenous serum albumin into the rat brain at various intervals after single-fraction irradiation by immunohistochemistry using a specific antibody.…”

Targeting classical but not neurogenic inflammation reduces peritumoral oedema in secondary brain tumours

“…All animals were sacrificed at this time point with 100% of animals showing evidence of tumour burden upon histological analysis. Walker 256 implantation models of secondary brain tumours have been described previously in the literature Jamshidi et al, 1992;Morreale et al, 1993). However tumours in the current study grew quicker than those reported previously.…”