| Objective: While basic studies have shown a significant protective effect of magnesium ions in models of cerebral ischemic disease,two large clinical trials of magnesium supplementation,IMAGES and FAST-MAG,showed no improvement in patient prognosis.We speculate that the permeability of the blood-brain barrier during systemic magnesium supplementation may have contributed to the results of the clinical trials.In this experiment,we investigated the effects of both lateral ventricular administration and intraperitoneal administration on ischemic injury in rats with focal cerebral ischemia.Methods: Male SD rats were randomly divided into sham-operated group,model group,intraperitoneal administration group,and lateral ventricular low,medium and high concentration groups.The Middle Cerebral Artery Occlusion(MCAO)rat model was prepared by reference to the Longa wire embolization method,and the embolus was removed and reperfused 90 min after embolization.The effect of magnesium supplementation on cerebral ischemic injury in rats was evaluated in three aspects: 1.Neurobehavioral evaluation: the neurological function of rats in each group was evaluated by the Longa method;the postoperative changes in motor ability,perception and coordination were evaluated by the rotating bar test and the sticky strip test.2.Histological evaluation: TTC stained to mark infarction and compare the percentage of brain infarct volume;H-E stained to evaluate the changes of brain tissue damage under the microscope in each group of rats;3.Changes in oxidative stress-related proteins: Paraffin sections were prepared from the perfused brains of each group of rats,and immunohistochemical stained was performed to observe the the expression of inducible Nitric Oxide Synthase(i NOS),an oxidative stress marker protein;fresh brain tissue was subjected to immunoprotein blotting to observe the expression of Glutathione Peroxidase 1(GPx1),an antioxidant protein.Results: 1.neurobehavioral evaluation.Neurological symptom scores:compared with the model group(2.38±0.52 points),the scores of longa method in each concentration group of the lateral ventricle were significantly decreased(P<0.05).Stick-turning experiment: The motor ability of rats was impaired after MCAO.Compared with the model group,the motor ability of the middle and high concentration groups of the lateral ventricle was significantly improved(P<0.05),and the improvement effect of the intraperitoneal administration group was not significant.Sticky strip experiment: perceptual coordination was impaired in rats after MCAO.Compared with the model group,each administration group showed a reduction in the time to perceive and tear off the sticky strips in the bilateral forelimbs of rats,and the perceptual coordination ability was improved(P<0.05).2.Histological changes: TTC staining,the volume of cerebral infarction was reduced in each administration group compared with the model group(30.84±3.59%).The most significant effect was in the lateral ventricular concentration group,with a 51.61% reduction(p<0.05).H-E staining showed that the tissue cells in the model group were necrotic and lysed in the form of vacuoles,with disorganized fiber arrangement and nuclei consolidation and fragmentation.The lateral ventricular administration group significantly improved the post-ischemic nerve cell injury.3.The expression of oxidative stress marker proteins: In the cortical and striatal regions,the number of i NOS-positive cells was significantly increased in the model group,while the number of positive cells in the lateral ventricular administration group was reduced compared with the model group.There were significant reductions in the lateral ventricular mid-concentration group,58.18% and 63.04%,respectively(P<0.05).Expression of the antioxidant protein GPx1: The expression level of GPx1 decreased by 64.16% in the model group compared with the control group(P<0.05);Compared with the model group,the expression was upregulated in all the administered groups(P<0.05),with 74.38% upregulation of protein expression in the concentration group in the lateral ventricle.Conclusions:(1)Lateral ventricular administration of magnesium sulfate after acute cerebral ischemia can reduce the volume of cerebral ischemic infarction and improve the neurological function of rats after ischemia.(2)Compared with intraperitoneal administration,the lateral ventricular administration of magnesium sulfate can reduce the production of i NOS,increase the expression of GPx1,reduce the effect of oxidative stress on neuronal cells,exert neuroprotective effects,and improve neurological injury after ischemia. |
