Administration Of Magnesium Sulfate To The Lateral Ventricles Exerts Neuroprotective Effects In Rats With Focal Cerebral Is Chemia

Objective:Two large clinical trials,IMAGES and FAST-MAG,showed that magnesium supplementation did not improve patient outcomes,and the permeability ability of magnesium ions to the blood-brain barrier after systemic magnesium supplementation in the hyperacute phase of cerebral ischemia was considered to be one of the reasons that may affect the efficacy of clinical trials.We explored the neuroprotective effects of magnesium supplementation during the acute phase after focal cerebral ischemia in rats by administering magnesium sulfate to the lateral ventricles.Methods:Male SD rats with the administration channel placed in the lateral ventricle were subjected to MCAO model by reference to the Longa wire thrombosis method 7 days later,and the rats were extubated and reperfused 90 min after infarction.Animals were randomly divided into sham,model,intraperitoneal,and lateral ventricles（set gradient concentrations）.1.Evaluation of the effect of the placement channel on rats:the rotarod test detects the locomotor activity of rats before and after tube placement.2.Behavioral evaluation:the neurological changes of rats in each group were evaluated by Longa’s method score.3.Histological evaluation:H-E sections and TTC stained tissues were taken from brains and the changes in cerebral infarction volume were detected.4.Mechanism study on the cerebroprotective effect of magnesium supplementation after ischemia:by immunohistochemistry,the expression of NMDA receptor subunit p-NR1-positive cells and the expression of microglial marker protein Iba-1 were observed.Results:1.There was no significant difference in locomotor activity before and after placement of a drug delivery channel in the lateral ventricle.2.Neurological deficit scores:after 24 h of reperfusion,the Longa’s method scores of the middle and high concentration of lateral ventricles were decreased by 45.0%（P<0.05）compared with those of the model group（2.20±0.45）.3.Histological evaluation:H-E staining,compared with the model group（38.26±0.68%）,the middle concentration group（26.01±1.75%）and the high concentration group（25.22±1.26%）in the lateral ventricle significantly reduced the cerebral infarct size（P<0.01）,and the additional TTC staining,compared with the model group（39.02±3.63%）,the middle concentration group（22.79±6.64%）in the lateral ventricle significantly reduced the cerebral infarct volume（P<0.01）.4.Immunohistochemical staining was performed to observe the expression of NMDA receptor subunit p-NR1-positive cells and the expression of microglial marker protein Iba-1.The number of p-NR1-positive cells in the middle and high concentration groups in the lateral ventricle increased by 71.4%,40.2%（P<0.01）in the striatal region and 66.3%,83.2%（P<0.01）in the cortical region compared with that in the model group at 24 h after reperfusion（10.58±0.52 cells/mm²）;The number of cortical activated Iba-1⁺microglia was decreased by 33.1%,66.9%,48.9%in the low,medium,and high-concentration groups in the lateral ventricles,respectively（P<0.01）.Conclusions:1.Intracerebroventricular injection of magnesium sulfate can improve infarct volume and improve motor function in rats with cerebral ischemia.2intracerebroventricular injection of medium and high concentration of Mg SO₄ameliorated brain tissue damage under H-E staining at 24 h of ischemia,while significantly restoring p-NR1 expression compared with intraperitoneal injection of Mg SO₄ and intracerebroventricular injection of low concentration MgSO₄.3.Amelioration of postischemic injury by intracerebroventricular magnesium sulfate injection may be closely related to the recovery of p-NR1 expression and the reduction of Iba-1⁺activation during the acute phase of cerebral ischemia.