MgSO₄ Treatment Preserves the Ischemia-Induced Reduction in S-100 Protein Without Modification of the Expression of Endothelial Tight Junction Molecules

The aim of this work was to evaluate the effect of magnesium sulphate (MgSO ₄ ) administration on blood-brain barrier (BBB) permeabilization after cerebral hypoxia-ischemia (HI) induced by partial occlusion of the umbilical cord of premature fetal lambs. We also characterized BBB dysfunction in terms of the levels of expression of a panel of BBB proteins; Occludin, Claudin, Zona Occludens-1, Zonula Occludens-2, VE-cadherin and beta-catenin. Lambs were assigned to: Control group: non-injured animals, 0 h post-partial cord occlusion (0h-PCO) group: animals subjected to 60 min HI and sacrificed just after the insult, 3h-PCO group: HI injured animals resuscitated and managed on ventilation for 3 hours and MgSO ₄ group: animals which received a dose of 400 mg/kg MgSO ₄ after the HI event and managed on ventilation for 3 hours. Brains were fixed and blocks processed for S-100 protein immunohistochemistry. Other brains were dissociated and processed for S-100 and BBB protein immunochemistry for analysis by flow cytometry. The percentage of S-100 positive cells was found to be dramatically reduced in all studied brain tissues in the 3h-PCO group with respect to the other groups. No differences were found in the percentage or mean intensity of BBB protein immunolabeled cells among the groups. In the MgSO ₄ group, the percentage of S-100 positive cells 3 h after the HI event was similar to the control group. These results suggest that MgSO ₄ treatment preserves the ischemia-induced reduction in S-100 protein without modification in the expression of endothelial tight junction molecules. We speculate that MgSO ₄ treatment confers neuroprotection by restoration of blood brain permeability in hypoxia-ischemia.