Neuroprotective Effect Of Magnesium-L-threonate Before Opening Of The Blood Brain Barrier To The Magnesium In Transient Focal Cerebral Ischemia In Rats

OBJECTIVE Clinical trial indicated that magnesium sulfate has no significant effect on stroke patients.Based on previous studies on the permeability of blood brain barrier(BBB)in magnesium sulfate and pathophysiology of BBB damage after cerebral ischemia,it is that the permeability of BBB to magnesium was not high in acute phase when the BBB was not damaged after cerebral ischemia may be one of the influences.This study was to explore the time of BBB opening to the magnesium firstly.Then to investigate the neuroprotective effect of magnesium-L-threonate which is high permeability to BBB before opening of the BBB to the magnesium in transient focal cerebral ischemia in rats.METHODS 1.The time of BBB opening to the magnesium.The model of middle cerebral artery occlusion(MCAO)was established to transient focal ischemia by placing an intraluminal filament at the origin of left middle cerebral artery for 90 minutes.Magnesium sulfate was given by intraperitoneal injection at 3h,6h,12 h,24h of ischemia and magnesium concentration of cerebrospinal fluid(CSF)was collected and detected to make sure the time of blood brain barrier opening to the magnesium.2.The neuroprotective effect of magnesium-L-threonate before opening of the blood brain barrier to the magnesium in focal cerebral ischemia in rats.The rats were divided randomly into: sham operation,model,magnesium sulfate and magnesium-L-threonate treatment groups.The brain was taken at 24 h after ischemia.Then the2,3,5-triphenyltetrazolium chloride(TTC)was used to mark the focal ischemic cerebral infarction in rats,and the infarct volume was calculated.RESULTS 1.The time of blood brain barrier(BBB)opening to the magnesium.Compare to normal group,there is no significant different in magnesium concentration in CSF of 3h and 6h after ischemia.While Magnesium concentration was significantly increased in CSF of 12 h and 24 h after ischemia(P < 0.05).2.The neuroprotective effect of magnesium-L-threonate in focal cerebral ischemia in rats.Infarction was not seen in the sham operation group.The percentage ofinfarct volume was 41.9 ± 4.3% in sham operation group.While the percentage of infarct volume in magnesium sulfate and magnesium-L-threonate treatment groups was 22.2 ± 3.4% and 13.8 ±3.8%.Compared with the normal group,the volume of cerebral infarction in model group increased significantly(P< 0.01).Compared with the model group,the volume of cerebral infarction decreased significantly in magnesium sulfate and magnesium-L-threonate treatment groups(P<0.01).While the volume of cerebral infarction decreased more significantly difference in magnesium-L-threonate treatment groups than in magnesium sulfate group(P < 0.05).CONCLUSIONS 1.The time of blood brain barrier(BBB)opening to the magnesium is between 6 and 12 h after focal cerebral ischemia in rats.2.The neuroprotective effect of magnesium-L-threonate before opening of the BBB to the magnesium is more effective than magnesium sulfate in transient focal cerebral ischemia in rats.