scholarly journals Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral Ischemia in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hui Hu ◽  
Xiao ou Sun ◽  
Fang Tian ◽  
Hao Zhang ◽  
Qing Liu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Therapeutic Window ◽  
Vehicle Group ◽  
Neuroprotective Effects ◽  
Therapeutic Benefits ◽  
Neurobehavioral Deficits ◽  
Cerebral Artery Occlusion

Previous report has indicated that isosteviol has neuroprotective effects. However, isosteviol was administered preventively before ischemia and the inclusion criteria were limited. In the present study, a more soluble and injectable form of isosteviol sodium (STVNA) was administered intravenously hours after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its neuroprotective effects in rats. The rats were assessed for neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct volume quantification and histology evaluation. STVNA 10 mg·kg−1can significantly reduce the infarct volumes compared with vehicle in animals subjected to tMCAO and is twice as potent as previously reported. Additionally, the therapeutic window study showed that STVNA could reduce the infarct volume compared with the vehicle group when administered 4 hours after reperfusion. A similar effect was also observed in animals treated 4 hours after pMCAO. Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment significantly reduced neurobehavioral impairments. The number of restored NeuN-labeled neurons was increased and the number of TUNEL positive cells was reduced in animals that received STVNA treatment compared with vehicle group. All of these findings suggest that STVNA might provide therapeutic benefits against cerebral ischemia-induced injury.

Abstract W MP94: Neuroprotective Effect of Isosteviol Sodium on Focal Cerebral Ischemia in Rats

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Hui Hu ◽  
Qing Liu ◽  
Fang Tian ◽  
Hao Zhang ◽  
DaiXin Qu ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Therapeutic Window ◽  
Vehicle Group ◽  
Signal Pathways ◽  
Neuroprotective Effects ◽  
Doppler Flowmetry ◽  
Neurobehavioral Deficits ◽  
Dosage Study

Background & Objective: Isosteviol is a molecule derived from Steviaside which has been used as sweetener worldwide. In this study, sodium salt of isosteviol (STVNA) was given i.v. in rats hours after the transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its therapeutic neuroprotective effects. Methods: In male Sprague-Dawley rats 2 hours tMCAO with reperfusion or pMCAO was induced and ischemia were confirmed by a laser doppler flowmetry simultaneously. In dosage study, animals were divided into 6 groups: sham, vehicle, or treatment with STVNA at dosage of 1, 5, 10mg•kg-1 or Edaravone 1 hour before the onset of reperfusion. In therapeutic time window study, animals were divided into 5 groups: sham, vehicle, STVNA (10mg•kg-1) at 0, 2 or 4 hours after reperfusion. In pMCAO study, animals were divided into 5 groups: sham, vehicle or STVNA (10mg•kg-1) at 1, 2 or 4 hours after ischemia. Rats were assessed for neurobehavioral deficits after 24 hours and sacrificed for infarct volume quantitation and histology evaluation. Proteomic analysis of the penumbra area in some rats used a Snaps G2x MS-TOF system. Results: In dosage study, the infarct volume of STVNA 10mg•kg-1 group was significantly less compared either with the vehicle group (22±2% vs 41±5%, p< 0.01) or with the Edaravone group (22±2% vs 30±3%, p< 0.05 ). The therapeutic window study shows that STVNA treated at 4h after reperfusion still has significant effects than vehicle group (32±4% vs 41±5%, p<0.05). In pMCAO study, the infarct volume of STVNA at 4h still decreased comparing the vehicle group(29±5% vs 50±6%, p< 0.05).In all STVNA treated groups the neurobehavioral deficits were significantly improved, and there are more restored NeuN-labeled neurons and alleviated TUNEL positive cells in penumbra in comparing with the vehicle group. Proteomic analysis indicates that proteins involved in various inflammations associated signal pathways were dramatically increased by tMCAO, and then were greatly reduced after treated with STVNA. Conclusions: STVNA exhibited remarkable neuroprotective effects when administered 4 hours after pMCAO or 4 hours after reperfusion of tMCAO. Since STVNA has low systemic toxicity, it may be a better alternative for the treatment of stroke.

scholarly journals Cortical Spreading Depression Protects against Subsequent Focal Cerebral Ischemia in Rats

1996 ◽  
Vol 16 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Kazushi Matsushima ◽  
Matthew J. Hogan ◽  
Antoine M. Hakim
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Occipital Cortex ◽  
Artery Occlusion ◽  
Microdialysis Probe ◽  
Cerebral Artery Occlusion ◽  
Subcortical Infarct

The possibility that cortical spreading depression (CSD) may have neuroprotective action during subsequent focal cerebral ischemia was examined in rats. Three days before the imposition of focal cerebral ischemia CSDs were elicited by applying potassium chloride (KCl) for 2 h through a microdialysis probe implanted in the occipital cortex. Control animals were handled identically except that saline was infused instead of KCl. Focal ischemia was produced by the intraluminal suture method and cortical and subcortical infarct volumes were measured 7 days later. Neocortical infarct volume was reduced from 124.8 ± 49.5 mm3 in the controls to 62.9 ± 59.5 mm3 in the animals preconditioned with CSD (p = 0.012). There was no difference between the two groups in the subcortical infarct volume or in CBF, measured by the hydrogen clearance method, during or immediately after the ischemic interval. Our data indicate that preconditioning CSD applied 3 days before middle cerebral artery occlusion may increase the brain's resistance to focal ischemic damage and may be used as a model to explore the neuroprotective molecular responses of neuronal and glial cells.

scholarly journals Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via Targeting PPARγ

2016 ◽  
Vol 39 (4) ◽  
pp. 1339-1346 ◽  
Author(s):  
Lichun Pei ◽  
Songyan Meng ◽  
Weigang Yu ◽  
Qiujun Wang ◽  
Fangfang Song ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Protein Level ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Luciferase Assay ◽  
Cerebral Artery Occlusion

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in protecting against distinct brain damages, including ischemia. Our previous data have shown that the protein level of PPARγ is increased in the cortex after middle cerebral artery occlusion (MCAO); PPARγ up-regulation contributes to PPARγ activation and is effective in reducing ischemic damage to brain. However, the regulatory mechanism of PPARγ after focal cerebral ischemia in rats is still unclear. In this study, we evaluated the effect of microRNA on PPARγ in rats subjected to MCAO. Methods: Focal cerebral ischemia was established by surgical middle cerebral artery occlusion; the protein level of PPARγ was detected by Western blotting; the level of microRNA-383 (miR-383) was quantified by real-time PCR; the neurological outcomes were defined by infarct volume and neurological deficits. Luciferase assay was used to identify the luciferase activities of PPARγ and miR-383. Results: We showed here that miR-383 level was down-regulated in the ischemic hemisphere of rats 24h after MCAO. Overexpression of miR-383 by miR-383 agomir increased infarct volume and aggravated neurological damage. Administration of miR-383 antagomir had the opposite effects. Furthermore, we found that PPARγ protein was down-regulated by miR-383 overexpression, and up-regulated by miR-383 inhibition both in rat model of MCAO and in primary culture cells. Finally, we found that miR-383 suppressed the luciferase activity of the vector carrying the 3'UTR of PPARγ, whereas mutation of the binding sites relived the repressive effect of miR-383. Conclusion: Our study demonstrated that miR-383 may play a key role in focal cerebral ischemia by regulating PPARγ expression at the post-transcriptional level, and miR-383 may be a potential therapeutic target for stroke.

scholarly journals Intraventricular Brain-Derived Neurotrophic Factor Reduces Infarct Size after Focal Cerebral Ischemia in Rats

1997 ◽  
Vol 17 (5) ◽  
pp. 500-506 ◽  
Author(s):  
Wolf-R. Schäbitz ◽  
Stefan Schwab ◽  
Matthias Spranger ◽  
Werner Hacke
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Neurotrophic Factor ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 μg/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls ( P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 ± 27.1 mm3 in BDNF-treated animals and 139.2 ± 56.4 mm3 in controls (mean ± SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 ± 7.1 mm3 in BDNF-treated animals and 37.9 ± 19.8 mm3 in controls (mean ± SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

scholarly journals Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jin-Young Chung ◽  
Min-Wook Kim ◽  
Wooseok Im ◽  
In Koo Hwang ◽  
Moon-Suk Bang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Neuroprotective Effects ◽  
Adult Rat ◽  
Neurotrophin 3 ◽  
Exercise Induced ◽  
Cerebral Artery Occlusion

Neurotrophin-3 (NT-3) is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC) receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

scholarly journals Effect of combined therapy with hyperbaric oxygen and an antioxidant on infarct volume after permanent focal cerebral ischemia

2007 ◽  
pp. 369-373
Author(s):  
G Acka ◽  
A Sen ◽  
Z Canakci ◽  
S Yildiz ◽  
A Akin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Hyperbaric Oxygen ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Combined Therapy ◽  
Artery Occlusion ◽  
Control Group ◽  
Male Wistar Rats ◽  
Cerebral Artery Occlusion ◽  
Reduce Infarct Volume

The aim of the present study was to evaluate the efficiency of combination of hyperbaric oxygen (HBO) and an antioxidant on permanent focal cerebral ischemia. Male Wistar rats underwent permanent middle cerebral artery occlusion (MCAO). Then, animals were randomly assigned to one of four groups: the control group (n=9) received no treatment, HBO group (n=9) was treated for 90 min at 2.5 absolute atmosphere for 3 days, the U-74389G group (n=8) received single U-74389G injection (3 mg/kg), the HBO + U-74389G group (n=8) received both HBO and U-74389G treatments. Treatments were initiated within the first 10 min after MCAO. After 3 days, the infarct volumes in rat brains were measured. The infarct ratios were 25.6+/-6.5 % for the control group, 21.9+/-6.4 % for the HBO group, 15.7+/-5.7 % for U-74389G group and 12.5+/-3.8 % for HBO + U74389G group. The infarct volumes were significantly reduced in rats treated with U-74389G (p<0.05) and combination therapy (p<0.05). HBO failed to reduce infarct volume significantly. We concluded that 1) U-74389G is more beneficial than HBO on permanent MCAO in rats, and 2) a combined therapy failed to significantly improve infarct volume more than either single treatment.

Abstract 154: Protection from Transient Focal Cerebral Ischemia by Transfusion of Polynitroxylated Pegylated Hemoglobin

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jian Zhang ◽  
Suyi Cao ◽  
Li Ma ◽  
Carleton J Hsia ◽  
Raymond C Koehler
Keyword(s):  
Vascular Function ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Border Region ◽  
Therapeutic Window ◽  
Laser Doppler Flow ◽  
Transient Focal Cerebral Ischemia ◽  
Cerebral Artery Occlusion ◽  
Hemispheric Infarct

Polynitroxylation of hemoglobin (Hb) confers superoxide dismutase and catalase mimetic activity and can protect neurons from native Hb and glutamate. Here, we determined if transfusion of polynitroxylated pegylated Hb (PNPH) is protective in the rat filament model of 2 h of middle cerebral artery occlusion (MCAO). Transfusion of 10 ml/kg of PNPH at 20 min of MCAO reduced the median infarct volume in cerebral cortex from 40% (37-47% interquartile range; n=10) in controls to 3% (0-7%; n=10; P<0.001) with PNPH and in striatum from 78% (66-88%) to 34% (0-37%; P<0.001). The therapeutic window was evaluated in a second experiment. Compared to the control median hemispheric infarct volume of 22% (13-34%; n=15), infarct volume was reduced to 7% (3-13%; n=14; P<0.05) when PNPH was transfused at 4 h after MCAO (2 h of reperfusion) but not significantly when transfused at 6 h (8%; 3-35%; n=14) or at 8 h (12%; 10-25%; n=14) after MCAO. To determine whether PNPH might act by promoting vasodilation, pial arteriolar diameter in the distal MCA border region was measured in closed cranial windows during MCAO. With no transfusion, MCAO induced an initial dilation (36±5%; ±SD; n=8) that subsided by 2 h (5±11%). With PNPH transfusion at 20 min of MCAO, the initial dilation (31±8%; n=7) was better maintained at 2 h (21±11%; P<0.02). To determine whether delaying PNPH transfusion until 90 min of MCAO would improve penumbral perfusion, laser-Doppler flow (LDF) was measured in the ischemic border region where the reduction in LDF was less severe than in the core. LDF significantly increased from 48±18% of the pre-ischemic baseline to 67±21% (P<0.005). Thus, PNPH transfusion has a significant therapeutic window for protection from transient MCAO and may act, in part, by stabilizing vascular function and improving collateral blood flow.

scholarly journals Rapid Tolerance to Focal Cerebral Ischemia in Rats is Attenuated by Adenosine A1 Receptor Antagonist

2002 ◽  
Vol 22 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Michiko Nakamura ◽  
Kazuhiko Nakakimura ◽  
Mishiya Matsumoto ◽  
Takefumi Sakabe
Keyword(s):  
Receptor Antagonist ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Ischemic Tolerance ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Induced Tolerance ◽  
Cerebral Artery Occlusion

Two types of ischemic tolerance in the brain, rapid and delayed, have been reported in terms of the interval between the conditioning and test insults. Although many reports showed that delayed-phase neuroprotection evoked by preconditioning is evident after 1 week or longer, there have been a few investigations about rapidly induced tolerance, and the reported neuroprotective effects become ambiguous 7 days after the insults. The authors examined whether this rapid ischemic tolerance exists after 7 days of reperfusion in a rat focal ischemic model, and investigated modulating effects of the adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine). Preconditioning with 30 minutes of middle cerebral artery occlusion reduced infarct volume 7 days after 180 minutes of subsequent focal ischemia given after 1-hour reperfusion. The rapid preconditioning also improved neurologic outcome. These beneficial effects were attenuated by pretreatment of 0.1 mg/kg DPCPX, which did not influence the infarct volume after conditioning (30 minutes) or test (180 minutes) ischemia when given alone. The results show that preconditioning with a brief focal ischemia induces rapid tolerance to a subsequent severe ischemic insult, the effect of which is still present after 7 days of reperfusion, and that the rapid ischemic tolerance is possibly mediated through an adenosine A1 receptor–related mechanism.

scholarly journals Neuroprotective Effects of a Novel Nitrone, NXY-059, after Transient Focal Cerebral Ischemia in the Rat

1999 ◽  
Vol 19 (7) ◽  
pp. 778-787 ◽  
Author(s):  
Satoshi Kuroda ◽  
Ryoichi Tsuchidate ◽  
Maj-Lis Smith ◽  
Kirk R. Maples ◽  
Bo K. Siesjö
Keyword(s):  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Recovery Period ◽  
Artery Occlusion ◽  
Transfer Constant ◽  
Neuroprotective Effects ◽  
Transient Focal Cerebral Ischemia ◽  
Therapeutic Opportunity ◽  
Cerebral Artery Occlusion ◽  
Antiischemic Effect

Recent results have demonstrated that the spin trapping agent α-phenyl- N- tert-butyl nitrone (PBN) reduces infarct volume in rats subjected to 2 hours of middle cerebral artery occlusion, even when given 1 to 3 hours after the start of recirculation. In the current study, the authors assessed the effect of NXY-059, a novel nitrone that is more soluble than PBN. Loading doses were given of 0.30, 3.0, or 30 mg · kg−1 followed by 0.30, 3.0, or 30 mg · kg−1 · h−1 for 24 or 48 hours. Dose–response studies showed that when treatment was begun 1 hour after recirculation, 0.30 mg · kg−1 had a small and 30 mg · kg-i a marked effect on infarct volume. At equimolar doses (3.0 mg · kg−1 for NXY-059 and 1.4 mg · kg−1 for PBN), NXY-059 was more efficacious than PBN. Similar results were obtained when a recovery period of 7 days was allowed. The window of therapeutic opportunity for NXY-059 was 3 to 6 hours after the start of recirculation. Studies of the transfer constant of [14C]NXY-059 showed that, in contrast to PBN, this more soluble nitrone penetrates the blood-brain barrier less extensively. This fact, and the pronounced antiischemic effect of NXY-059, suggest that the delayed events leading to infarction may be influenced by reactions occurring at the blood–endothelial interface.

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