A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-l protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.
Young-Kyung Lee;Chul Hwan Kim;Su Young Shin;Buyng Su Hwang;Min-Jeong Seo;Hye Jin Hwang;Kyung-Min Choi;Jin-Woo Jeong
Proceedings of the Plant Resources Society of Korea Conference
/
2020.08a
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pp.76-76
/
2020
Stachys sieboldii Miq. (chinese artichoke), which has been extensively used in oriental traditional medicine to treat of ischemic stroke; however, the role of Stachys sieboldii Miq. (SSM) in cerebral ischemia/reperfusion (I/R) injury is not yet fully understood. In the current study, the neuroblastoma cell line (SH-SY5Y) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury in vitro model. The results showed that SSM improved OGD/R-induced inhibitory effect on cell viability of SH-SY5Y Cells. SSM displayed anti-oxidative activity as proved by the decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in OGD/R-induced SH-SY5Y Cells. In addition, cell apoptosis was markedly decreased after SSM treatment in OGD/R-induced SH-SY5Y Cells. The up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, SSM protected human neuroblastoma SH-SY5Y cells from OGD/R-induced injury via preventing mitochondrial-dependent pathway through scavenging excessive ROS, suggesting that SSM might be a potential agent for the ischemic stroke therapy.
The purpose of this study was to identify the effect of cerebral ischemia on affected(Lt) and unaffected(Rt) side of soleus, plantaris and gastrocnemius muscle mass and determine the effect of exercise on affected and unaffected side on soleus, plantaris and gastrocnemius muscle mass during acute stage of stroke. Sixteen male Sprague-Dawley rate with 200-270g body weight were randomly divided into three groups: control, stroke, and exercise after stroke(St+Ex) group. The control group received sham operation and the stroke group and St+Ex group received transient right MCA(middle cerebral artery) occlusion operation. The St+Ex groups ran on a treadmill for 20min/day at 10m/min and $10^{\circ}$ grade for 6days. During the experimental period body weight and diet intake was measured every morning. On the 7th day after operation, muscles were dissected from both affected and unaffected side of hindlimb. Cerebral infarction of stroke and St+Ex groups were identified by staining with TCC for 30 minutes. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. Significance was accepted at the level of p<0.05. The results were summarized follows : 1) There were no significant difference of the body weight on the first day of experiment among 3 groups. Whereas on the 7th day, the body weight of both stroke group and St+Ex group were significantly smaller than that of control group. Body weight of St+Ex group on the 7th day tended to be larger than that of stroke group. 2) Total diet intake of both stroke group and St+Ex group were also significantly smaller than that of control group. While total amount of diet intake in St+Ex group tended to be larger than that of stroke group. 3) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of control group and the weight of soleus and plantaris muscle of affected side in stroke group tended to decrease compared to that of control group. 4) The weight of plantaris muscle of unaffected side in stroke group significantly decreased compared to that of control group and the weight of soleus and gastrocnemius muscle of unaffected side in stroke group tended to decrease compared to those of control group. 5) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of unaffected side and there was no significant difference of the weight of soleus and plantaris muscle in stroke group between affected side and unaffected side. 6) The weight of soleus, plantaris and gastrocnemius muscle of both affected side and unaffected side in St+Ex group had a tendency of increase compared to those of stroke group. The relative weight of soleus and gastrocnemius muscle of affected side and soleus muscle of unaffected side in St+Ex group had a tendency to increase compared to those of stroke group. Based on these results, exercise during acute stage of stroke might attenuate muscle atrophy of both affected and unaffected side of hindlimb muscles.
This study investigated whether ferulic acid modulates the heme oxygenase (HO)-1 and HO-2 expression in middle cerebral artery occlusion (MCAO)-induced brain injury. Rats (Sprague-Dawley, male) were treated with vehicle or ferulic acid (100 mg/kg, i.v.) before MCAO, and cerebral cortex tissues were collected 24 h after MCAO. This study clearly confirmed the protective effects of ferulic acid during MCAO-induced damage using hematoxylin and eosin staining. MCAO induces nuclear chromatin condensations and necrotic changes with scalloped shrunken form. However, ferulic acid prevented MCAO-induced histopathological changes. HO-1 and HO-2 expression levels were measured using reverse-transcription PCR and Western blot analyses. HO-1 levels were decreased in vehicle-treated animals after MCAO, whereas this decrease in HO-1 levels was attenuated by ferulic acid treatment. However, the level of HO-2 was consistently maintained in the cerebral cortex of vehicle- and ferulic acid-treated animals after MCAO. These results demonstrated that ferulic acid regulates HO-1 expression in ischemic brain injury, while ferulic acid do not modulate HO-2 expression in MACO. In conclusion, these findings suggest that ferulic acid exerts a neuroprotective effect by preventing the MCAO-induced decrease of HO-1 expression.
This work aimed to study whether rice bran extract fermented with Lactobacillus plantarum (LW) promotes functional recovery and reduces cognitive impairment after ischemic brain injury. Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) in rats. Four groups were studied, namely the (1) sham, (2) vehicle, (3) donepezil, and (4) LW groups. Animals were injected with LW once a day for 7 days after middle cerebral artery occlusion. LW group showed significantly improved neurological function as compared to the vehicle group, as well as enhanced learning and memory in the Morris water maze. The LW group showed the greatest functional recovery. Moreover, the LW group showed an enhanced more survival cells anti-apoptotic effect in the cortex and neural cell densities in the hippocampal DG and CA1. In addition, this group showed enhanced expression of neurotrophic factors, antioxidant genes, and the acetylcholine receptor gene, as well as synaptophysin (SYP), Fox-3 (NeuN), doublecortin (DCX), and choline acetyltransferase (ChAT) proteins. Our findings indicate that LW treatment showed the largest effects in functional recovery and cognitive improvement after ischemic brain injury through stimulation of the acetylcholine receptor, antioxidant genes, neurotrophic factors, and expression of NeuN, SYP, DCX, and ChAT.
Moyamoya disease is an unusual cerebrovascular disorder characterized by occlusive intimal dysplasia of the distal internal carotid and proximal cerebral arteries, but the etiology remains unclear. Angiographic characteristics include bilateral stenosis or occlusion of the terminal portions of the intracranial internal carotid arteries and bilateral development of fine collateral vessels at the base of the brain known as ‘Moyamoya vessels’. Cardiac surgery using cardiopulmonary bypass due to coronary artery disease and others among patients with moyamoya disease is very rare, and cardiac surgery for such patients has a potential risk of intraoperative and perioperative brain ischemia. We successfully treated a patient who underwent artrial septal defect closure and coronary artery bypass graft using the cardiopulmonary bypass, so we report this case with a brief literature review.
Objective : Persistent trigeminal artery variant (PTAV) is an anastomosis between the internal carotid artery (ICA) and the cerebellar artery without any interposing basilar artery segment. We discuss its probable embryological origin and emphasize clinical implications. Methods : Retrospectively 1250 conventional cerebral angiograms and 2947 cranial magnetic resonance angiographies (MRAs) were evaluated for the patients with PTAV. Results : Five patients (four men and one woman, 23 to 76 years of age, median age 65 years) had a PTAV. Three patients who underwent MRA had a PTAV (3/2947=0.1%). Four of the patients who underwent cerebral angiography had a PTAV (4/1250=0.32%). Two of 143 patients who underwent both conventional angiography and cranial MRA showed PTAV. The PTAV was an incidental finding in all five patients. The PTAV originated from the cavernous segment of the left ICA in four patients and from the cavernous segment of the right ICA in one patient. The terminal branch of the PTAV was the anterior inferior cerebellar artery (AICA) and superior cerebellar artery (SCA) in two patients and the AICA only in the other three patients. Conclusion : Neurosurgeons should be aware of possible presence of PTAV. Manipulation of this vessel during a surgical approach to the parasellar region and percutaneous gasserian ganglion procedure may result in hemorrhage or ischemia.
Xuesaitong Ruanjiaonang (XR), a soft capsule containing Panax notoginseng saponins as main ingredients, is believed to remove extravasated blood and increase cerebral blood flow by improving blood circulation, and therefore, has been used in China to treat ischemic stroke or hemiplegia caused by cerebral thrombosis. To characterize pharmacological actions of XR, the present study evaluated its effects on neuronal cell damage induced by various oxidative insults or excitotoxic amino acids in primary cultured rat cortical cells. The neuronal cell viability was not affected by XR with the exposure for 2 h at the concentrations tested in this study ($10{\sim}1000\;{\mu}g/ml$). However, significant reduction of the cell viability was observed when the cultured cells were exposed to XR at $1000\;{\mu}g/ml$ for 24 h. XR was found to concentration-dependently inhibit the oxidative neuronal damage induced by $H_{2}O_2$, xanthine/xanthine oxidase or $Fe^{2+}$/ascorbic acid. In addition, it dramatically inhibited the excitotoxic damage induced by glutamate or N-methyl-D-aspartate (NMDA). We found that the NMDA-induced neurotoxicity was inhibited more effectively and potently than the glutamate-induced toxicity. Moreover, XR was found to exert mild inhibition of lipid peroxidation induced by $Fe^{2+}$/ascorbic acid in rat brain homogenates and some 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate neuroprotective and antioxidant effects of XR, showing inhibition of oxidative and excitotoxic damage in the cultured cortical neurons, as well as inhibition of lipid peroxidation and its radical scavenging activity. Considering that excitotoxicity and oxidative stress pl ay crucial roles in neuronal cell damage during ischemia and reperfusion, these results may provide pharmacological basis for its clinical usage to treat ischemic stroke.
Objective : Although stent-assisted coiling (SAC) has been reported to be safe and effective in treating wide-necked aneurysms, the technique has procedure-related complications. Thus, we reported our experiences of SAC using the Neuroform Atlas stent in treating wide-necked aneurysms and evaluated the incidence of and risk factors for procedure-related complications. Methods : From March 2018 to August 2019, we treated 130 unruptured wide-necked aneurysms in 123 patients with Neuroform Atlas stents. Angiographic results and clinical outcomes were reviewed retrospectively. Clinical and angiographic follow-up were performed in all cases (mean, 12.4 months) after the procedure. Results : There were eight cases (6.2%) of procedure-related complications (two dissections, five thromboembolisms, and one hemorrhage) and two (1.5%) of delayed complications (one ischemia and one hemorrhage). There was one case (0.8%) of failure of stent deployment and one (0.8%) of suboptimal positioning of the stent. Follow-up angiography showed complete obliteration in 103 (79.2%), residual neck in 16 (12.3%), and residual aneurysm in 11 cases (8.5%). Aneurysm locations in the middle cerebral artery (odds ratio [OR], 2.211; p=0.046) and the anterior communicating artery (OR, 2.850; p=0.039) were associated with procedure-related complications on univariate analysis. However, no independent risk factor for procedure-related complications was noted in multivariate analysis. Conclusion : The Neuroform Atlas showed a high rate of technical success. Good clinical and radiographic outcomes in early follow-up suggests that the device is feasible and safe. SAC of aneurysms on the middle cerebral artery or anterior communicating artery may require more attention to prevent possible procedure-related complications.
Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced inflammation and oxidative stress and improved white matter integrity in a neonatal rodent model. Seven-day old Sprague-Dawley pups were exposed to H/I. Paeoniflorin (6.25, 12.5, or 25 mg/kg body weight) was administered every day via oral gavage from postpartum day 3 (P3) to P14, and an hour before induction of H/I. Pups were sacrificed 24 h (P8) and 72 h (P10) following H/I. Paeoniflorin reduced the apoptosis of neurons and attenuated cerebral infarct volume. Elevated expression of cleaved caspase-3 and Bad were regulated. Paeoniflorin decreased oxidative stress by lowering levels of malondialdehyde and reactive oxygen species generation and while, and it enhanced glutathione content. Microglial activation and the TLR4/NF-κB signaling were significantly down-regulated. The degree of inflammatory mediators (interleukin 1β and tumor necrosis factor-α) were reduced. Paeoniflorin markedly prevented white matter injury via improving expression of myelin binding protein and increasing O1-positive olidgodendrocyte and O4-positive oligodendrocyte counts. The present investigation demonstrates the potent protective efficiency of paeoniflorin supplementation against H/I-induced brain injury by effectually preventing neuronal loss, microglial activation, and white matter injury via reducing oxidative stress and inflammatory pathways.
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