Comparision Study Of Neuroprotection Effect In Magnesium-L-threonate And Magnesium Sulfate In Focal Cerebral Ischemia Injury

OBJECTIVE: A part of basic research confirmed that the magnesium sulfate reduce cerebral ischemia injured effectively.According to the results of clinical research,magnesium sulfate does not reduce patients’ disability and mortality with cerebral apoplexy.Study reported that adding magnesium sulfate can’t increase the concentration of magnesium ions in cerebralspinal fluid(CSF).Basing on the pathological process of blood-brain barrier(BBB)after cerebral ischemia,we speculated that the magnesium sulfate are difficult passing BBB into brain.Literature reported that magnesium-L-threonate has high permeability of blood brain barrier.This study compared the neuroprotection effect of magnesium-L-threonate and magnesium sulfate after focal cerebral ischemia.METHODS: 1.The effect of magnesium-L-threonate and magnesium sulfate on the volume of cerebral infarction in focal cerebral ischemia rats.We refered the Longas’ method to establish the middle cerebral artery occlusion(MCAO)model.The rats were divided randomly into: sham operation,model,magnesium sulfate and magnesium-L-threonate treatment groups.The 2,3,5-triphenyltetrazolium chloride(TTC)was used to mark the focal ischemic cerebral infarction in rats at 24 h after ischemia reperfusion.2.The effect of magnesium-L-threonate and magnesium sulfate on the neurobehavioral ability of ischemic rats.Neurological defects were scored in rats after ischemia reperfusion in rats(i.e.Longas score).3.The influence of magnesium-L-threonate and magnesium sulfate on the phosphorylated N-methyl-D-aspartate receptor 1(p-NR1)positive cells expression.At 6h,12 h and 24 h after cerebral ischemia,we gave experimental rats perfusion in brain and made paraffin sections.Through the Hematoxylin – Eosin(H-E)staining,we observed histological change and determined the ischemic penumbra area.And we counted the p-NR1 positive cells in ischemia penumbra area by immunohistochemical staining.RESULTS: 1.Infarct volume measurement.Infarction was not seen in the sham operation group.Compared with the model group(17.96± 2.99%),the volume of cerebral infarction decreased significantly in magnesium sulfate(9.45±2.77%,P<0.01)and magnesium-L-threonate treatment groups(6.17± 2.43%,P<0.01).While the infarct volume decreased more significantly in magnesium-L-threonate treatment groups than in magnesium sulfate group(P < 0.05).2.Neurobehavior score.The neurobehavior score of sham operation group was 0.Compared with model group(1.8±0.1)and magnesium sulfate(1.7±0.1)group,the neurobehavior score was lower in magnesium-L-threonate treatment group(1.3±0.1,P<0.05).3.Positive cells count.Compared with sham group(75.7±4.9/mm2),the density of positive cells were significantly lower at 6h(27.7±1.8/mm2),12h(20.3±3.2/mm2)and 24h(35.5±1.3/mm2)after ischemia in model group(P<0.01).Compared with model group,the density of positive cells of magnesium sulfate treatment groupwere significant increased at 12h(39.3±5.4/mm2)after cerebral ischemia.And the density of positive cells of magnesium-L-threonate treatment group positive cells were more significantly at 6h(41.7±1.9/mm2)and 12h(45.3±2.4/mm2)than model group(P<0.05).CONCLUSIONS: 1.Magnesium sulfate reduced the rats’ infarction volume significantly after focal cerebral ischemia.Magnesium-L-threonate reduced the rats’ infarction volume and improve their behavior significantly after cerebral ischemia.2.The machenisium of neuroprotection of Magnesium-L-threonate may be related to the expression of NR-1.