Cerebral Ischemia In Rats Research Articles

Stroke Literature Synopsis (Preclinical).

Stroke Literature Synopsis (Preclinical).

Comparison of the efficacies of Huangqi-Danshen herbal pair compatibility with wild-simulated and transplanted Astragali Radix based on a novel metabolomics strategy

In China, Astragali Radix (Huangqi, HQ) has been extensively applied as a bulk medication. Currently, two forms of HQ are available on the market: wild-simulated HQ (WHQ) and transplanted HQ (THQ), However, it is uncertain whether the two are equally effective. This study compared the differences in their effects by investigating the efficacy of the herbal combination of Astragali Radix and Salvia miltiorrhiza (Huangqi-Danshen, HD) in the prevention of focal cerebral ischemia (FCI) rats. To achieve the more accurate differential metabolites related to FCI, we proposed a tissue-targeted metabonomic study in conjunction with a novel screening strategy based on ultra-high performance liquid chromatography coupled with the quadrupole-Exactive mass spectrometry (UHPLC-Q Exactive MS). The appropriate thresholds of four screening factors (variable importance in the projection (VIP), log2 absolute value of fold change (|log2(FC)|), -In(p-value) and ǀp(corr)ǀ) and their best combination were determined by comparing R2X, R2Y, and Q2 of the orthogonal to partial least squares discriminant analysis (OPLS-DA) models. Eleven metabolites were significantly screened and associated with focal cerebral ischemia through the novel metabolomics strategy. The transplanted HD (THD) had a better callback effect on these eleven metabolites compared with the wild-simulated HD (WHD), especially γ-L-Glutamyl-l-glutamic acid, proline, maleic acid, and S-(Formylmethyl)glutathione. Additionally, the optimal WHD and transplanted THD doses were found to be medium and high. Pathway analysis revealed that middle-dose WHD and high-dose THD largely participated in four and six metabolic pathways, respectively. The results further revealed that THD was better than WHD against focal cerebral ischemia. These findings provided a unique perspective on an integrated comparison of the efficacy difference between WHQ and THQ. In addition, the tissue-targeted metabonomic study gave us new insights into the pathological mechanism of focal cerebral ischemia.

Cornel Iridoid Glycoside Alleviates Microglia-Mediated Inflammatory Response via the NLRP3/Calpain Pathway.

Vascular dementia (VaD) is associated with cerebral hypoperfusion, which results in long-term cognitive impairment and memory loss. Cornel iridoid glycoside (CIG) is the major active constituent isolated from the ripe fruit of Cornus officinalis. Previous studies have shown that CIG enhances neurological function in VaD rats. In the present research, we attempted to clarify the molecular processes underlying the role of CIG in neuroinflammation in VaD. We created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries (2VO) and then treated rats with different concentrations of CIG. Comprehensive analyses revealed that CIG ameliorated myelin integrity and neuronal loss. Furthermore, we also found that CIG inhibited polarized microglia activation and attenuated inflammasome-mediated production of proinflammatory cytokines in BV2 microglia cells induced by LPS/IFN-γ and in the brains of 2VO rats. To further elucidate the role of CIG in microglia-mediated inflammatory response, we investigated the expression and activity of calpain. CIG inhibited the expression and activity of calpain 1/2, which was characterized by decreased calpastatin and spectrin αII expression. In particular, intra- and extracellular calpain 1 levels were reduced by CIG. However, CIG showed weak interaction with calpain 1. In addition, we found that CG administration significantly repressed the assembly of the NOD-like receptor protein 3 (NLRP3) inflammasome, including NLRP3, ASC, and caspase-1. In conclusion, our knowledge of the mechanisms by which CIG regulates NLRP3/calpain signaling to influence inflammatory responses offers further insights into potential therapeutic strategies to treat VaD.

Early Rehabilitation Exercise after Stroke Improves Neurological Recovery through Enhancing Angiogenesis in Patients and Cerebral Ischemia Rat Model.

Among cerebrovascular diseases, ischemic stroke is a leading cause of mortality and disability. Thrombolytic therapy with tissue plasminogen activator is the first choice for clinical treatment, but its use is limited due to the high requirements of patient characteristics. Therefore, the choice of neurological rehabilitation strategies after stroke is an important prevention and treatment strategy to promote the recovery of neurological function in patients. This study shows that rehabilitation exercise 24 h after stroke can significantly improve the neurological function (6.47 ± 1.589 vs. 3.21 ± 1.069 and 0.76 ± 0.852), exercise ability (15.68 ± 5.95 vs. 162.32 ± 9.286 and 91.18 ± 7.377), daily living ability (23.37 ± 5.196 vs. 66.95 ± 4.707 and 6.55 ± 2.873), and quality of life (114.39 ± 7.772 vs. 168.61 ± 6.323 and 215.95 ± 10.977) of patients after 1 month and 3 months, and its ability to promote rehabilitation is better than that of rehabilitation exercise administered to patients 72 h after stroke (p < 0.001). Animal experiments show that treadmill exercise 24 h after middle cerebral artery occlusion and reperfusion can inhibit neuronal apoptosis, reduce the volume of cerebral infarction on the third (15.04 ± 1.07% vs. 30.67 ± 3.06%) and fifth (8.33 ± 1.53% vs. 30.67 ± 3.06%) days, and promote the recovery of neurological function on the third (7.22 ± 1.478 vs. 8.28 ± 1.018) and fifth (4.44 ± 0.784 vs. 6.00 ± 0.767) days. Mechanistic studies have shown that treadmill exercise increases the density of microvessels, regulates angiogenesis, and promotes the recovery of nerve function by upregulating the expression of vascular endothelial growth factor and laminin. This study shows that rehabilitation exercise 24 h after stroke is conducive to promoting the recovery of patients’ neurological function, and provides a scientific reference for the clinical rehabilitation of stroke patients.

Obesity induces extracellular vesicle release from the endothelium as a contributor to brain damage after cerebral ischemia in rats

ABSTRACT Objectives Cerebral ischemia is the most common cause of disability, the second most common cause of dementia, and the fourth most common cause of death in the developed world [Sveinsson OA, Kjartansson O, Valdimarsson EM. Heilablóðþurrð/heiladrep: Faraldsfræði, orsakir og einkenni [Cerebral ischemia/infarction - epidemiology, causes and symptoms]. Laeknabladid. 2014 May;100(5):271–9. Icelandic. doi:10.17992/lbl.2014.05.543]. Obesity has been associated with worse outcomes after ischemia in rats, triggering proinflammatory cytokine production related to the brain microvasculature. The way obesity triggers these effects remains mostly unknown. Therefore, the aim of this study was to elucidate the cellular mechanisms of damage triggered by obesity in the context of cerebral ischemia. Methods We used a rat model of obesity induced by a 20% high fructose diet (HFD) and evaluated peripheral alterations in plasma (lipid and cytokine profiles). Then, we performed cerebral ischemia surgery using two-vessel occlusion (2VO) and analyzed neurological/motor performance and glial activation. Next, we treated endothelial cell line cultures with glutamate in vitro to simulate an excitotoxic environment, and we added 20% plasma from obese rats. Subsequently, we isolated EVs released from endothelial cells and treated primary cultures of astrocytes with them. Results Rats fed a HFD had an increased BMI with dyslipidemia and high levels of proinflammatory cytokines. Glia from the obese rats exhibited altered morphology, suggesting hyperreactivity related to neurological and motor deficits. Plasma from obese rats induced activation of endothelial cells, increasing proinflammatory signals and releasing more EVs. Similarly, these EVs caused an increase in NF-κB and astrocyte cytotoxicity. Together, the results suggest that obesity activates proinflammatory signals in endothelial cells, resulting in the release of EVs that simultaneously contribute to astrocyte activation.

The Regulation of miR-206 on BDNF: A Motor Function Restoration Mechanism Research on Cerebral Ischemia Rats by Meridian Massage.

As a frequent disease affecting the nervous system, cerebral infarction has emerged as a major cause of disability and elicits disorders in motor, sensation, and cognition as sequelae. No clear mechanism has been known in meridian massage despite it having been proved to be an effective therapeutic option. The study was carried out to explore the treatment of meridian massage on cerebral ischemia in rats and its effects on motor function restoration and nerve cell's ultrastructure in the ischemic territory. The alleviated nerve damages and recovered injured brain tissues were found in the cerebral infarction model of SD rats after meridian massage. Expressions of miR-206 and the brain-derived neurotrophic factor (BDNF) in the gastrocnemius muscle were all well observed. The effects of miR-206 on BDNF were testified by overexpressed and interfered miR-206 in the C2C12 myoblast. Moreover, at the molecular level, meridian massage downregulated miR-206 expression at an elevated level of BDNF. Consequently, meridian massage exerts a vital role in promoting cerebral ischemia restoration, which is expected to provide an addition to the application of traditional Chinese medicine (TCM) in the reconstruction and treatment of cerebral ischemia.

Protective Effect of Neferine in Permanent Cerebral Ischemic Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms.

Permanent cerebral ischemia is a consequence of prolonged cerebral artery occlusion that results in severe brain damage. Neurotoxicity occurring after ischemia can induce brain tissue damage by destroying cell organelles and their function. Neferine is a natural compound isolated from the seed embryos of the lotus plant and has broad pharmacological effects, including blockading of the calcium channels, anti-oxidative stress, and anti-apoptosis. This study investigated the ability of neferine to reduce brain injury after permanent cerebral occlusion. Permanent cerebral ischemia in rats was induced by instigation of occlusion of the middle cerebral artery for 24h. The rats were divided into 6 groups: sham, permanent middle cerebral artery occlusion (pMCAO), pMCAO with neferine and nimodipine treatment. To investigate the severity of the injury, the neurological deficit score and morphological alterations were investigated. After 24h, the rats were evaluated to assess neurological deficit, infarct volume, morphological change, and the number of apoptotic cell deaths. In addition, the brain tissues were examined by western blot analysis to calculate the expression of proteins related to oxidative stress and apoptosis. The data showed that the neurological deficit scores and the infarct volume were significantly reduced in the neferine-treated rats compared to the vehicle group. Treatment with neferine significantly reduced oxidative stress with a measurable decrease in 4-hydroxynonenal (4-HNE), nitric oxide (NO), neuronal nitric oxide (nNOS), and calcium levels and an upregulation of Hsp70 expression. Neferine treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-2. This study suggested that neferine had a neuroprotective effect on permanent cerebral ischemia in rats by diminishing oxidative stress and apoptosis.

Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats.

SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke.

The Regulation of Autophagy by p38 MAPK-PPARγ Signaling During the Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning.

Several studies indicated that autophagy activation participates in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP). However, the mechanism of autophagy activation during the process still remains unclear. The present study aimed to evaluate the role of p38 MAPK-peroxisome proliferator-activated receptor γ (PPARγ) signaling cascade in autophagy during the CIP-induced BIT. The results shown that, initially, autophagy activation was observed after CIP in the model of global cerebral ischemia in rats, as was indicated by the upregulation of Beclin 1 expression, an increase in LC3-II/LC3-I ratio, the enhanced LC3 immunofluorescence, and a rise in the number of autophagosomes in the neurons of the hippocampal CA1 area. Besides, the inhibitor of autophagy 3-methyladenine obliterated the neuroprotection induced by CIP. Furthermore, the upregulation of p-p38 MAPK and PPARγ expressions was earlier than autophagy activation after CIP. In addition, pretreatment with SB203580 (the inhibitor of p38 MAPK) reversed CIP-induced PPARγ upregulation, autophagy activation, and neuroprotection. Pretreatment with GW9662 (the inhibitor of PPARγ) reversed autophagy activation and neuroprotection, while it had no effect on p-p38 MAPK upregulation induced by CIP. These data suggested that the p38 MAPK-PPARγ signaling pathway participates in autophagy activation during the induction of BIT by CIP.

Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the RhoA/ROCK pathway

BackgroundMicroglia can be activated as proinflammatory (M1) phenotypes and anti-inflammatory (M2) phenotypes after stroke. Parthenolide (PTL) has anti-inflammatory and protective effects on neurological diseases, but until now, the exact mechanisms of these processes after stroke have been unclear. The purpose of this study was to determine the effect of PTL on microglial polarization after stroke and its target for inducing microglial polarization. MethodsTriphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and neurological evaluation were performed in a focal transient cerebral ischemia rat model. The human microglia exposed to lipopolysaccharide (LPS) was used for in vitro experiments. Microglial polarization was assessed by RT-PCR and immunostaining. Inflammatory cytokine assays and western blotting were used to investigate the molecular mechanisms underlying PTL-mediated microglial polarization in vivo and in vitro. ResultsPTL significantly reduced cerebral infarction and neuronal apoptosis in rats with cerebral ischemia, reduced the level of inflammatory factors and alleviated neurological deficits. PTL treatment decreased the expression of microglia/macrophage markers in M1 macrophages and increased the expression of microglia/macrophage markers in M2 macrophages after stroke, which induced the transformation of microglia cells from the M1 phenotype to the M2 phenotype. Furthermore, PTL significantly reduced RhoA/ROCK-NF-κB pathway activity and downregulated the effects of pentanoic acid (ROCK agonist). ConclusionsPTL has been shown to mediate neuroinflammation and protect against ischemic brain injury by regulating microglial polarization via the RhoA/ROCK pathway.

Echinacoside Alleviates Cognitive Impairment in Cerebral Ischemia Rats through α 7nAChR-Induced Autophagy.

To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats. The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively. ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01). ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.

Comparative study on brain pharmacokinetics of Buyang Huanwu Decoction in normal and cerebral ischemia rats using brain microdialysis combined with LC-MS/MS

ObjectiveTo conduct a comparative study on the brain pharmacokinetics of seven ingredients (i. e. senkyunolide A, ferulic acid, formononetin, calycosin, ononin, calycosin-O-β-D-glucopyranoside, and paeoniflorin), which were the compounds of Buyang Huanwu Decoction (BHD), in normal and cerebral ischemia rats administrated intragastrically with BHD. MethodsThe samples of normal and permanent middle cerebral artery occlusion (pMCAO) rats were collected by using brain microdialysis technique. The concentrations of seven ingredients were determined by the HPLC-MS/MS method. After the BHD were administrated intragastrically to the rats for seven consecutive days, brain microdialysis probes were inserted into the hippocampus of rats, and then the brain microdialysates were collected at 20 min time intervals for 5 h. The separation of the seven ingredients and internal standard (IS) was carried out on an ACQUITY UPLC BEH C18 (2.1 mm × 100 mm, 1.7 μm) chromatographic column, using a mobile phase consisting of acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid) for gradient elution within 13 min. The ionization was conducted using an ESI source in positive ion mode. Multiple reaction monitoring mode was used for quantification of ingredients in BHD. ResultsLinearity, accuracy, precision, matrix effect and stability of LC-MS/MS method were all satisfactory, successfully applied to compare the pharmacokinetics of the analytes between normal and model rats after intragastric administration of BHD. Compared with the normal group, the model group after the administration of the BHD showed that T1/2 of formononetin and ononin were longer, and except for calycosin-O-β-D-glucopyranoside (P < 0.01), there was no significant difference between the normal group and the model group. The Cmax of senkyunolide A and calycosin of model group were increased, while the Tmax of senkyunolide A was decreased, and except for the Tmax of PF, the differences between the two groups were statistically significant (P < 0.01). ConclusionThe LC-MS/MS method combined with microdialysis was successfully applied to the comparative study of brain pharmacokinetics of seven ingredients in BHD. After intragastric administration of BHD, there were differences in the pharmacokinetics of seven ingredients in the brain hippocampus between normal rats and model rats, probably related to the characteristics of the ingredients and the effects of cerebral ischemia on the absorption and distribution of the ingredients.

Endothelial Protection of Vasoactive Intestinal Peptide Enhances Angiogenesis Mediated by eNOS Pathway Following Focal Cerebral Ischemia in Rats

Endothelial Protection of Vasoactive Intestinal Peptide Enhances Angiogenesis Mediated by eNOS Pathway Following Focal Cerebral Ischemia in Rats

Neuroprotective Effect of Alpha-Pinene on Focal Cerebral Ischemia in Rats

Neuroprotective Effect of Alpha-Pinene on Focal Cerebral Ischemia in Rats

Synthesis and evaluation of cerebroprotective activity of novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives containing residues of amino acids and dipeptides

Neurodegenerative processes of the central nervous system are an important socially significant problem of modern society. They cause many diseases, such as Alzheimer's disease and cerebral ischemia, which significantly reduce the quality of human life and can lead to disability or death. The aim of this study was to synthesize novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives with the remains of neuroactive amino acids and dipeptides in order to investigate their cerebroprotective properties. As a result of the study, 13 novel 6,7-dimetho-xyquinazolin-4(3H)-one derivatives were synthesized. Cerebral ischemia in rats was reproduced by irreversible right-sided occlusion of the middle cerebral artery using the Tamura method, and the area of brain necrosis was evaluated. Cognitive functions were evaluated in the Y-maze test. Among the studied quinazolinone derivatives, compounds 3i, 3j and 3k have the most pronounced cerebrotropic activity, which is not inferior to ethylmethylhydroxypyridine succinate in terms of pharmacological activity, making them promising objects for further research.

Pharmacokinetic-pharmacodynamic modeling analysis for hydroxysafflor yellow A-calycosin in compatibility in normal and cerebral ischemic rats: A comparative study.

Astragalus and Safflower are commonly used in the treatment of stroke. Studies have shown that their two active components, hydroxysafflor yellow A (HSYA) and calycosin (CA), have protective effects on cerebral ischemia-reperfusion injury (I/R). However, the pharmacokinetic-pharmacodynamic (PK-PD) modeling study of the combination of the two components has not been reported in rats. The study aimed to perform combined PK-PD modeling of HSYA and CA in normal and cerebral ischemia model rats to explain quantitatively their time-concentration-effect relationship. To make the middle cerebral artery occlusion (MCAO) model. SD rats were randomly divided into normal treated group (NTG) (n=6), model group (MDG) (n=6) and model treated group (MTG) (n=6). Plasma was collected from the mandibular vein after 0, 2, 5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 180, and 240min after intravenous administration. Rats in NTG and MTG were administered the same dose of HSYA (5mg/kg) and CA (8mg/kg) by tail vein injection. HPLC-VWD method was used for detection and analysis. Simultaneously, ELISA was performed to detect the levels of IL-1β and caspase-9 in rat plasma at different time points. The improvement in the above indicators was compared after administration. Lastly, after combining the pharmacokinetic parameters and pharmacodynamic indicators in vivo, DAS 3.2.6 software was used to fit the PK-PD model. The MCAO model was successfully established. Compared to NTG, there was a significant difference (P<0.05) in t1/2α, t1/2β, V1, V2, CL1, CL2, AUC(0-t), AUC (0-∞), and K12 of MTG for HSYA, and there was a significant difference (P<0.05) in t1/2α, V1, CL1, AUC(0-t), AUC (0-∞), and K10 of MTG for CA. Compared to NTG, the PK parameters of t1/2α, V1, V2, CL1, and K10 were higher for HSYA in MTG, while AUC(0-t), AUC (0-∞), K12, and K21 were lower; the PK parameters of t1/2α, V1, V2, AUC(0-t), and AUC(0-∞) were higher for CA in MTG, while CL1, CL2, K10, K12, and K21 were lower. Also, the results of PD showed extremely significant differences in the levels of caspase-9 and IL-1β at the different time points in MTG (P<0.01) compared with 0min. The levels of caspase-9 and IL-1β in NTG rats showed little fluctuation and were relatively stable; however, their levels in MTG showed a downward trend with time. There were highly significant differences in the levels of each of the pharmacodynamic indicators at every time point between NTG and MTG (P<0.01). The PK-PD model of the combined administration of HSYA and CA was successfully established in rats, and the differences in pharmacodynamic and pharmacokinetic properties between the normal and cerebral ischemic rats were evaluated. Based on comprehensive data analysis, we found that the combination of HSYA and CA may exert protective effects against I/R injury in rats via anti-apoptotic and anti-inflammatory pathways. The study provided additional insights into the development of drugs for ischemic stroke as well as the design of appropriate dosing regimens.

Specific bio-functional CBD-PR1P peptide binding VEGF to collagen hydrogels promotes the recovery of cerebral ischemia in rats.

Ischemic stroke was a leading cause of death and long-term disability. It was an effective way to improve cerebral ischemia injury by promoting angiogenesis and neuroprotection. Vascular endothelial growth factor (VEGF) was a potent pro-angiogenic factor, and had neuroprotective effect. A short peptide (PR1P) derived from the extracellular VEGF-binding glycoprotein-Prominin-1 was reported to specifically bind to VEGF. In order to realize sustained release of VEGF, a bio-functional peptide-CBD-PR1P was constructed, which target VEGF to collagen hydrogels to limit the diffusion of VEGF. When the collagen hydrogels loading with CBD-PR1P and VEGF were injected into the cerebral ischemic cortex, increased angiogenesis, decreased apoptosis and enhanced neurons survival were observed in the ischemic area, that promoted the motor functional recovery of cerebral ischemic injury. Thus, this targeting delivery system of VEGF provided a promising therapeutic strategy for cerebral ischemia.

Effects of pretreatment of ethanolic extract of Siegesbeckia pubescens Makino on cerebral ischemia in rats

BackgroundCerebral ischemia is characterized by inadequate blood supply to the brain to fulfill its metabolic demand. It is a leading cause of stroke. The objective of this study aimed to elucidate the effects of ethanolic extract of Siegesbeckia pubescens (EESP) Makino against cerebral ischemia in rats. MethodsSixty male Sprague-Dawley (SD) rats were distributed into 5 groups (n = 12) viz., low dose (2.5 g/kg/day) EESP group, high dose (5 g/kg/day) EESP group, Nimodipine group, untreated control, and sham-operated control. The reference group received 16 mg/kg/day of nimodipine, while the untreated and sham-operated control was given 20 ml/kg of distilled water. The middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia. On the 7th day of the trial, neurological evaluation and biochemical assays were carried out. After that, rats were sacrificed, and the brain infarct area was analyzed with image processing software. ResultsThe extent of neurologic deficits, infarct area, concentration of superoxide dismutase (SOD), and malondialdehyde (MDA) was significantly altered by the EESP when compared with untreated control and Sham-operated control. ConclusionsTaken together, these results reported protective effects of EESP on cerebrovascular ischemia that perhaps correlate with its mechanism of free radical scavenging. Our findings may provide insight into treating cerebral ischemia and give a new research era for further study.

Downregulation of mitochondrial pyruvate carrier 2 aggravates neuronal injury in the cortex following cerebral ischemia in rat

Cerebral ischemia is one of the most common disabling and lethal diseases worldwide, but its underlying mechanisms remain unclear. Mitochondrial pyruvate carrier 2 (MPC2), a subunit of MPC complex, plays pivotal roles in coordinating glycolytic and mitochondrial activities. In the present study, the expression of MPC2 was significantly reduced in the ischemic cerebral cortex of rats at 24 h after bilateral internal carotid artery occlusion (BICAO), and in the cortical neurons after 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation treatment. After MPC2 gene knockdown, the number and expression of neurons were remarkably decreased in the ischemic cerebral cortex of BICAO rats and OGD-treated neurons. UK5099 significantly reduced the number, expression and viability of OGD-treated neurons, and resulted in a significant decrease in length of neurite. Using RNA-sequencing (RNA-seq) technique, we further identified MPC2-related differential genes in the ischemic cerebral cortex of BICAO rats. In conclusion, our results suggested that the decrease in MPC2 expression aggravated ischemic injury, and MPC2-related genes might be a novel therapeutic target for cerebral ischemia.

COMPREHENSIVE ASSESSMENT OF NEUROLOGICAL DEFICIT AND ITS CORRECTION WITH PIR-10 COMPOUND IN EXPERIMENTAL FOCAL CEREBRAL ISCHEMIA OF RATS

Introduction: Correction of motor dysfunction resulting from focal cerebral ischemia is one of the significant problems of pharmacology and experimental therapy. Pyrimidine derivatives in the experiment on rats previously showed cerebroprotective activity, as a result of which it was decided to test the PIR-10 compound for the ability to reduce neurological deficit. Methods: A study was conducted to assess the effect of pyrimidine derivative (PIR-10 50 mg/kg) on neurological deficiency in the conditions of focal cerebral ischemia in rats. The study used mature male Wistar rats weighing 220-240 g (n=40). Focal cerebral ischemia was reproduced by coagulation of the left middle cerebral artery (anesthesia chloralhydrate 350 mg/kg). Neurological deficits were assessed using the McGraw, Combs and D'alecy, Garcia scales. Results: The studied compound PIR-10 contributes to the reduction of neurological deficits in all selected schools in comparison with the control group of animals (McGraw by 68% (p&lt;0,05), Combs and D'alecy by 4,3 times (p&lt;0,05), Garcia by 84% (p&lt;0,05)). In addition, the results obtained after administration of PIR-10 to rats showed a statistically significantly difference from the group of rats receiving a reference drug cavinton. However, complete recovery of motor functions after modeling focal cerebral ischemia was not observed in any group of rats. Conclusion: The PIR10 compound is able to partially correct the neurological deficit that occurs in conditions of cerebral circulatory insufficiency, surpassing the activity of the reference drug cavinton.