Lactation diminishes lesion-induced permeability of tracers into the brain

Diminished sensitivity to kainic acid (KA) lesioning action is present in the hippocampus of the lactating dam. Given that KA can alter blood-brain barrier (BBB) permeability, we investigated whether lactation would protect BBB permeability after treatment with this neurotoxin. Adult virgin or lactating (13-15 days pp) female Wistar rats were injected with an i.p. (10 mg/kg b.w.) or i.c.v. (100 ng/1 μl) KA dose. Control groups received a similar volume of vehicle. BBB permeability was assessed by an injection of fluorescent FITC-conjugated dextran tracer (40 kDa, 50 mg/500 μl) or of 4% Evans blue dye (500 μl), given 24 h after KA administration. Extravasation of dye or tracer was detected in virgin but not in lactating rats exposed to KA. In particular, increased extravasation of FITC-dextran was detected in the hippocampal subfields CA1 and CA3 and in the cerebral cortex of virgin rats that received KA, while lactating rats showed increased label for FITC-dextran only in the cerebral cortex. Western blot analysis of tight junction proteins showed a decrease of claudin-5 and occludin but not of zonula occludens-1 in the hippocampus of both virgin and lactating rats. These results allow us to conclude that the BBB of lactating rats is less sensitive to KA lesioning action in comparison to that of virgin rats by mechanisms different than those of tight junction proteins.