Figure 2.

Genetic obesity promotes blood–brain barrier breakdown. (a) Penetration of sodium fluorescein (NaFl), a low molecular weight fluorophore that does not pass the intact BBB, is more evident on hippocampal sections from vehicle-treated db/db mice (db/Veh). Increased NaFl penetrance was observed relative to vehicle-treated Wt mice (Wt/Veh) and db/db mice administered the PKCβ inhibitor Enzastaurin (db/Enz). (b) Quantitative fluorometry in hippocampal extracts reveals that hippocampal fluorescein penetrance is significantly increased in db/Veh mice relative to db/Enz mice and Wt/Veh controls. This pattern was not evident in cortical extracts, suggestive of regional differences in vulnerability of the BBB. (c) Western blotting for the tight junction proteins claudin 5 and occludin revealed PKCβ-dependent reductions in tight junction protein expression in db/Veh mice. (d) Representative images of western blot membranes for claudin 5 and occludin. For all graphs, bars depict the mean of (n = 6–8) mice per group, error bars represent the sem, and asterisks (*) denote statistical significance at p < 0.05 following one-way ANOVA with Bonferonni’s post hoc.