The effects of point-source electroporation on the blood-brain barrier and brain vasculature in rats: An MRI and histology study

Abstract

When applying electroporation to the brain, it is important to understand the effects on the blood-brain barrier (BBB) and brain vasculature. Here we studied the effects of point-source electroporation on rats’ brains as a function of time from treatment using conventional contrast-enhanced MRI and treatment response assessment maps (TRAMs), enabling depiction of subtle BBB disruption and differentiating contrast agent clearance from accumulation. Effects on vessels were also studied using Lectin staining.The TRAMs revealed that conventional contrast-enhanced MRI underestimates BBB disruption volume by nearly a factor of two, and that despite significant enhancement on standard MRI immediately post electroporation, there was no contrast accumulation in the tissue (clearance was faster than accumulation). Histology revealed significant increased vessel coverage in the treated striatum (40 ± 24% p < 0.03) immediately post electroporation, suggesting vasodilatation. Two-three hours post electroporation, both conventional MRI and TRAMs showed minor BBB disruption and histology showed decreased vessel coverage (56 ± 16%, p < 0.01), suggesting vasoconstriction. Four hours post electroporation, despite minor enhancement, the TRAMs showed significant BBB disruption with contrast accumulation, lasting over 24 h, with decreasing volumes. These results suggest that electroporation triggers several unique brain vascular mechanisms and that the optimal time window for drug administration is 4–6 h after electroporation.