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 (MgSO4) 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:



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 MgSO4 group: animals which received a dose of 400 mg/kg MgSO4 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 MgSO4 group, the percentage of S-100 positive cells 3 h after the HI event was similar to the control group. These results suggest that MgSO4 treatment preserves the ischemia-induced reduction in S-100 protein without modification in the expression of endothelial tight junction molecules. We speculate that MgSO4 treatment confers neuroprotection by restoration of blood brain permeability in hypoxia-ischemia.
Goñi-de-Cerio
Felipe
F
Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country, Leioa, Vizcaya, Spain.
Alvarez
Antonia
A
Alvarez
Francisco J
FJ
Rey-Santano
Maria C
MC
Alonso-Alconada
Daniel
D
Mielgo
Victoria E
VE
Gastiasoro
Elena
E
Hilario
Enrique
E
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D004727:Endothelium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D007150:Immunohistochemistry; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D062793:Occludin; D009418:S100 Proteins / Q000378:metabolism*; D012756:Sheep; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D008278:Magnesium Sulfate; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D062793:Occludin; D009418:S100 Proteins; D051176:beta Catenin; D000099152:Cadherin 5