Percentage Of Cerebral Infarction Volume Research Articles

MicroRNA-22 exerts its neuroprotective and angiogenic functions via regulating PI3K/Akt signaling pathway in cerebral ischemia-reperfusion rats.

The aims of this study were to study the effects of miR-2 on cerebral ischemia-reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34+ and VEGF+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia-reperfusion.

Influences of urinary kallidinogenase on neuronal apoptosis in cerebral infarction rats through Nrf2/ARE oxidative stress pathway.

To investigate the influences of urinary kallidinogenase on neuronal apoptosis in rats with cerebral infarction through the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) oxidative stress pathway. A total of 30 male rats were divided into group A (model control group), group B (rat model of cerebral infarction) and group C (rat model of cerebral infarction + medical treatment with urinary kallidinogenase). The percentage of cerebral infarct volume and the apoptosis of brain cells in the three groups of rats were detected via 2,3,5-Triphenyltetrazolium chloride (TTC) staining, the pathological morphology of brain tissues in the three groups of rats was observed via hematoxylin and eosin (HE) staining, and the protein levels of Nrf2 and superoxide dismutase 1 (SOD1) in the brain tissues in the three groups of rats were measured using the Western blotting assay. The degree of neurological deficit in group B was remarkably higher than that in group A (p<0.05), and it was markedly decreased in group C compared to that in group B, displaying statistically significant differences (p<0.05). Compared to that in group A, the cell apoptosis was significantly aggravated in group B, while a remarkably alleviated cell apoptosis was observed in group C compared to that of group B, and the differences were statistically significant (p<0.05). The cerebral infarct volume accounted for 34.87% of the whole brain volume in group B, and a mild cerebral infarction was detected in group C, with a percentage of cerebral infarct volume of 21.14%. Group B showed a more evident increase in the cerebral infarct volume than in group C (p<0.05). Compared to those of group A, pyknotic nuclei and neuron staining of brain tissue cells were evidently increased, and the neuronal cell injury was aggravated in group B. Moreover, prominently decreased pyknotic nuclei and neuron staining (p<0.05) as well as mild neuronal cell injury (p<0.05) were detected in group C compared to those in group B. The levels of Nrf2 and SOD1 protein in the brain tissues in group B were remarkably lower than those of group C (p<0.05). Urinary kallidinogenase can inhibit the neuronal apoptosis in rats and protect the rats from cerebral infarction, whose mechanism is associated with the activation of the Nrf2/ARE oxidative stress pathway.

MiR-183 inhibits microglia activation and expression of inflammatory factors in rats with cerebral ischemia reperfusion via NF-κB signaling pathway.

Ischemic stroke represents 87% of all strokes, and is the third leading cause of disability and mortality worldwide. The cause of ischemic stroke is the obstruction of blood flow through the artery that supplies oxygen-rich blood to the brain, with ischemia-reperfusion injury as its major cause. microRNAs (miRNA) are small non-coding RNAs, which serve important roles in the regulation of gene expression at the post-transcription level. The aim of the present study was to investigate the effect of miRNA-183 (miR-183) on microglia activation in rats with cerebral ischemia-reperfusion injury. To this end, a rat cerebral ischemia-reperfusion injury model was established. The results indicated that miR-183 expression was decreased by cerebral ischemia-reperfusion. In addition, treatment using miR-183 agomir significantly reduced the neurological function scores, percentage of cerebral infarction volume, and ionized calcium-binding adapter molecule-1 (IBA-1)-positive cells in the CA1 area of the hippocampus in rats subjected to cerebral ischemia-reperfusion injury, implicating a neuroprotective role for miR-183. MiR-183 agomir treatment also decreased the expression of pro-inflammatory-associated proteins interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Finally, the expression of the nuclear factor (NF)-κB p65 and IκBα was decreased and increased by miR-183 agomir treatment, respectively, indicating inhibition of the NF-κB signaling pathway. These observations suggest that miR-183 regulates the activation of microglia in rats with cerebral ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway.

LncRNA SNHG1 inhibits neuronal apoptosis in cerebral infarction rats through PI3K/Akt signaling pathway.

To investigate the effects of long non-coding ribonucleic acid (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on the neuronal apoptosis in rats with cerebral infarction through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Male Sprague Dawley (SD) rats were divided into M group (model control group), N group (rat model of cerebral infarction) and R group (rat model of cerebral infarction plus lncRNA SNHG1) and then treated accordingly. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was applied to detect the percentage of cerebral infarct volume and apoptosis of brain cells in the three groups of rats; hematoxylin and eosin (HE) staining was utilized to observe the pathological morphology of brain tissues, and Western blotting was performed to measure the protein levels of phosphorylated PI3K (p-PI3K) and p-Akt in the brain tissues. The degree of neurological deficit in the N group was much higher than that in the M group (p<0.05), and it was decreased markedly in the R group compared with that in the N group, with statistically significant differences (p<0.05). In comparison with that in the M group, the cell apoptosis was aggravated notably in the N group and alleviated remarkably in the R group, and the differences were statistically significant (p<0.05). In the N group, the cerebral infarct volume accounted for 33.67% of the whole brain volume, and mild cerebral infarction was detected in the R group, with a percentage of cerebral infarct volume of 20.15%. N group had a more prominent increase in the cerebral infarct volume than the R group (p<0.05). Compared with those in the M group, the pyknotic nuclei and neuron staining of brain tissues were increased significantly, and the neuronal cell injury was aggravated in the N group, while markedly reduced pyknotic nuclei and neuron staining (p<0.05), as well as mild neuronal cell injury (p<0.05), were detected in the R group. The levels of p-PI3K and p-Akt proteins in the brain tissues declined remarkably in the N group compared with those in the R group (p<0.05). The protective effect of lncRNA SNHG1 on the rats with cerebral infarction is correlated with the activation of the PI3K/Akt signaling pathway.

Effect of ulinastatin on expression of metabotropic glutamate receptor II during cerebral ischemia-reperfusion in rats

Objective To evaluate the effect of ulinastatin on the expression of metabotropic glutamate receptor Ⅱ (mGluRⅡ) during cerebral ischemia-reperfusion (I/R) in rats. Methods Forty-eight male Sprague-Dawley rats, aged 6-8 weeks, weighing 230-280 g, were divided into 3 groups (n=16 each) by a random number table method: sham operation group (S group), cerebral I/R group (I/R group) and ulinastatin group (U group). The model of cerebral I/R injury was established by occluding the right middle cerebral artery using a nylon thread with a rounded tip inserted into internal carotid artery and advanced cranially until resistance was met.Middle cerebral artery occlusion was maintained for 2 h followed by 24-h reperfusion.Ulinastatin 100 000 U/kg was injected via the tail vein immediately after onset of reperfusion in group U. The neurological deficit score (NDS) was assessed after 24 h of reperfusion.The rats were then sacrificed, and brain tissues were obtained for determination of brain infarction (by TTC staining), expression of IκB-α in cerebral ischemic penumbra (by Western blot) and expression of mGluR Ⅱ in cerebral ischemic penumbra (by immunofluorescent staining). The percentage of cerebral infarct volume was calculated. Results Compared with S group, the NDS and percentage of cerebral infarct volume were significantly increased, the expression of mGluRⅡ in cerebral ischemic penumbra was up-regulated, and the expression of IκB-α in cerebral ischemic penumbra was down-regulated in I/R and U groups (P<0.05). Compared with I/R group, the NDS and percentage of cerebral infarct volume were significantly decreased, the expression of mGluRⅡ in cerebral ischemic penumbra was down-regulated, and the expression of IκB-α in cerebral ischemic penumbra was up-regulated in U group (P<0.05). Conclusion The mechanism by which ulinastatin mitigates cerebral I/R injury may be related to inhibiting the expression of mGluR Ⅱ in cerebral ischemic penumbra of rats. Key words: Trypsin inhibitor; Reperfusion injury; Brain; Receptor, glutamate

Protective Effect of Ad-VEGF-Bone Mesenchymal Stem Cells on Cerebral Infarction.

To understand the mechanism of intracerebroventricular transplantation of vascular endothelial growth factor (VEGF) genemodified bone mesenchymal stem cells (BMSCs) in rats after cerebral infarction. The middle cerebral artery occlusion ischemia/reperfusion (MCAO I/R) model was established in rats using the Zea-Longa suture method. A recombinant adenovirus (Ad-VEGF) was engineered to express VEGF. The rats were divided into 3 groups. Control BMSC infected with control adenovirus (BMSC-Ad), BMSC infected by Ad-VEGF (BMSC-Ad-VEGF), and phosphate buffered saline (PBS) suspension were injected into the intracerebroventricular system of the rats in groups 1, 2 and 3 respectively, 24 hours after middle cerebral artery occlusion (MCAO). The neurological function of rats was evaluated with the modified Neurological Severity Scores (mNSS). The infarct volume of brain in rats was determined using 2,3,5-triphenyltetrazolium chloride (TTC) stain at 14 days. GFAP and pGSK3β expression of ischemic penumbra was determined using immunohistochemical method. GFAP, pAKT, AKT, and pGSK3β expressions were determined with Western blot. Functional improvement was accelerated in animals receiving BMSC-Ad, while improvement at all times between 7 days and 28 days post MCAO was significantly greater in animals transplanted with BMSC-Ad-VEGF than for other treated animals. The number of GFAP-labeled cells was prevented by post-ischemic BMSC-Ad-VEGF treatment; pMCAO activate the PI3K/AKT/GSK3β pathway to reduce reactive gliosis. Our findings demonstrate that PI3K/AKT/GSK3β pathway could reduce reactive gliosis, ameliorate neurological deficit, diminish the percentage of cerebral infarction volume in rats, and facilitate angiogenesis.

Protective Effect of Pharmacological Preconditioning of Total Flavones of Abelmoschl Manihot on Cerebral Ischemic Reperfusion Injury in Rats

The present study was to investigate the effect of pharmacological preconditioning of total flavones of abelmoschl manihot (TFA) on cerebral ischemic reperfusion injury in rats. Rat cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). The infarct size was determined by staining with 2,3,5-triphenyl tetrazalium chloride (TTC). The serum malonaldehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) levels were measured by using spectrophotometry; Inducible NO synthase (iNOS) mRNA expression was detected by RT-PCR method. The percentage of cerebral infarction volume was 28.1 +/- 0.8 in the model group, while TFA or nimodipine (Nim) pretreatment 36 hours prior to the ischemic insult significantly decreased the infarction volume. Increases of serum LDH activity and MDA level were observed after ischemia/reperfusion, but these changes were inhibited in rats pretreated with either TFA (20, 40, 80, 160 mg/kg) or Nim, indicating a delayed protective effect of TFA preconditioning on cerebral ischemic reperfusion injury. In addition, the serum NO level and the cerebral iNOS mRNA were up-regulated, suggesting a possible mechanism for the protective effect of TFA pretreatment on cerebral ischemic reperfusion injury.

Neuroprotection by 2-h Postischemia Administration of Two Free Radical Scavengers, α-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in Rats Subjected to Focal Embolic Cerebral Ischemia

Oxygen free radical generation may have important secondary damaging effects after the onset of cerebral ischemia. Free radical scavengers have been used successfully in attenuating neuronal damage in the reperfusion period in transient forebrain ischemia. There are limited data on effectiveness in models of focal ischemia. Two free radical scavengers, α-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), have been shown to reduce oxidative-stress-induced neuronal injury. Whereas PBN has been demonstrated to reduce infarct volume in focal ischemia, neuroprotection has not been evaluated with S-PBN. The present study was designed to evaluate the neuroprotective effect of PBN and S-PBN compared to vehicle in a focal embolic middle cerebral artery (MCA) cerebral ischemia model in rats. Wistar rats were randomly divided into three groups (n = 10 each group). Animals in the control group received vehicle and those in the treatment groups were treated with PBN or S-PBN (both 100 mg/kg/day × 3 days, intraperitoneally) starting 2 h after the introduction of an autologous thrombus into the right-side MCA. The neurological outcome was observed and compared before and after treatment and between groups. The percentage of cerebral infarct volume was estimated from 2,3,5-triphenyltetrazolium chloride stained coronal slices 72 h after the ischemic insult. Two-hour postischemia administration of PBN or S-PBN significantly improved neurobehavioral scores at 24 h following MCA embolization (both P < 0.01). The percentage of infarct volume for animals receiving vehicle was 32.8 ± 9.4%. Two-hour delayed administration of PBN and S-PBN achieved a 35.4% reduction in infarct volume in treatment groups when compared with animals receiving vehicle (PBN vs control, 21.2 ± 10.9% vs 32.8 ± 9.4%; P < 0.05; S-PBN vs control, 21.2 ± 13.1%, (P < 0.05). These data indicate that free radical generation may be involved in brain damage in this model and 2-h delayed postischemia treatment with PBN and S-PBN may have neuroprotective effects in focal cerebral ischemia. As S-PBN does not normally cross the blood–brain barrier, the neuroprotection evident in this study may be explained by entry into the brain via damaged vessels.