Focal Cerebral Ischemia Research Articles

Low-intensity focused ultrasound stimulation promotes stroke recovery via astrocytic HMGB1 and CAMK2N1 in mice

BackgroundLow-intensity focused ultrasound stimulation (LIFUS) has been developed to enhance neurological repair and remodelling during the late acute stage of ischaemic stroke in rodents. However, the cellular and molecular mechanisms...

MiR-96-5p alleviates cerebral ischemia-reperfusion injury in mice by inhibiting pyroptosis via downregulating caspase 1

Ischemic stroke is one of the leading causes of global mortality and disability. Nevertheless, successful treatment remains limited. In this study, we investigated the efficacy and the mechanism of miR-96-5p in protecting acute ischemic brain injury in adult mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice. MiR-96-5p or the negative control was administered via intracerebroventricular injection. The expression of pyroptosis-related genes and activation of various resident cells in the brain was assessed by RT-qPCR, western blot, immunohistochemistry, and immunofluorescence. Modified neurological severity score, rotarod test, cylinder test, brain water content, and cerebral infarction volume were used to evaluate the behavioral deficits and the severity of brain injury after MCAO. Flow cytometry, TUNEL staining, and Nissl staining were employed to assess the neuron damage. MiR-96-5p decreased markedly in the ischemic stroke model in vivo and in vitro. MiR-96-5p mimics suppressed the expression of caspase 1 and alleviated the apoptosis rate in OGD/R treatment N2a cells, however, the miR-96-5p inhibitor caused the opposite results. Intracerebroventricular delivery of miR-96-5p agomir significantly mitigated behavioral deficits, brain water content, and cerebral infarction volume after MCAO. In addition, treatment with miR-96-5p agomir downregulated the expression of caspase 1/cleaved caspase 1 and Gsdmd/Gsdmd-N, while alleviating the neuron damage. In summary, overexpression of miR-96-5p suppresses pyroptosis and reduces brain damage in the acute phase of ischemic stroke, providing new insight into the treatment of acute ischemic stroke.

Rat Model of Middle Cerebral Artery Occlusion.

Stroke is the third-leading cause of death and the leading cause of acquired adult disability worldwide. Several ischemic stroke models are currently available. However, mimicking focal cerebral ischemia (FCI) is the most common. The formation of an embolic or thrombotic occlusion at or near the middle cerebral artery causes most events in FCI. The current protocol closely mimics the etiology of human stroke and ensures that the results obtained are highly relevant. The method described in this protocol yields reproducible results. The success of this model in ischemic research can be examined through the utilization of Doppler blood flow imaging equipment.

Bifico Ameliorates Neurological Deficits After Ischemic Stroke in Mice: Transcriptome Profiling.

Evidence suggests that gut microbiota can affect various neurological diseases, including stroke. Stroke patients have an increase in harmful gut bacteria and a decrease in beneficial bacteria. This increases intestinal permeability, increases the risk of infection, and even affects many inflammatory factors. While probiotics may affect stroke prognosis by improving the gut environment. This study aimed to investigate the effect of probiotic Bifico on the neural function in mice after focal cerebral ischemia and explore its mechanisms of action. A focal cerebral ischemia model was established in mice. Four weeks before modeling, animals were divided into three groups: Stroke plus Vehicle group, Stroke plus Pre-Bifico group and Bifico group. The infarct volume and neurobehaviors were evaluated. Whole-gene expression profiling was performed at different days after treatment (D1, D7, D14, D28) by RNA-seq. Differentially expressed genes (DEGs) were the processed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Some inflammation and immune related genes were screened and their expression was analyzed. Compared to the Stroke plus Vehicle group and Bifico group, the infarct volume and neurological score were significantly reduced in the Pre-Bifico group. There were 2 DEGs at D1, 193 DEGs at D7, 70 DEGs at D28 between Stroke plus Pre-Bifico group and Stroke plus Vehicle group. For GO analysis, there were 139 significant terms at D7 and 195 at D28. For KEGG, there were 2 significant pathways at D7 and 9 at D28. Among 87 genes related to inflammation and immunity, 6 DEGs were identified. The expression of CCL9 was significantly elevated at most time points after stroke compared to the Stroke plus Vehicle group, while that of CCL6, CXCL10, CD48, CD72 and CLEC7A was highly expressed only in the recovery stage of stroke. Oral pre-treatment with Bifico for 28 days can reduce cerebral infarction and promote recovery of neurological function in stroke mice, which may be ascribed to the regulation of immunity and inflammation in the brain.

Neuroserpin and Extracellular Vesicles in Ischemic Stroke: Partners in Neuroprotection?

Ischemic stroke represents a significant global health challenge, often resulting in death or long-term disability, particularly among the elderly, where advancing age stands as the most unmodifiable risk factor. Arising from the blockage of a brain-feeding artery, the only therapies available to date aim at removing the blood clot to restore cerebral blood flow and rescue neuronal cells from death. The prevailing treatment approach involves thrombolysis by administration of recombinant tissue plasminogen activator (tPA), albeit with a critical time constraint. Timely intervention is imperative, given that delayed thrombolysis increases tPA leakage into the brain parenchyma, causing harmful effects. Strategies to preserve tPA's vascular benefits while shielding brain cells from its toxicity have been explored. Notably, administering neuroserpin (Ns), a brain-specific tPA inhibitor, represents one such approach. Following ischemic stroke, Ns levels rise and correlate with favorable post-stroke outcomes. Studies in rodent models of focal cerebral ischemia have demonstrated the beneficial effects of Ns administration. Ns treatment maintains blood-brain barrier (BBB) integrity, reducing stroke volume. Conversely, Ns-deficient animals exhibit larger stroke injury, increased BBB permeability and enhanced microglia activation. Furthermore, Ns administration extends the therapeutic window for tPA intervention, underscoring its potential in stroke management. Remarkably, our investigation reveals the presence of Ns within extracellular vesicles (EVs), small membrane-surrounded particles released by all cells and critical for intercellular communication. EVs influence disease outcome following stroke through cargo transfer between cells. Clarifying the role of EVs containing NS could open up urgently needed novel therapeutic approaches to improve post-ischemic stroke outcome.

Chicago sky blue 6B exerts neuroprotective and anti-inflammatory effects on focal cerebral ischemia

Brain ischemia is one of the leading causes of death and long-term disability worldwide. Cessation of the blood supply to the brain directly stimulates many pathological events, including glutamate overload and neuroinflammation. Glial cell activation occurs shortly after ischemia onset, resulting in the release of proinflammatory cytokines and exacerbation of the detrimental effects of neuroinflammation. Proinflammatory signals influence the infiltration of a wide range of immune cells, including neutrophils, T cells and monocytes/macrophages. In this study, we aimed to verify the potential anti-inflammatory effect of Chicago Sky Blue 6B (CSB6B) in a rat model of focal cerebral ischemia (90-minute middle cerebral artery occlusion). CSB6B was administered 2 h before (pretreatment) or 1.5 h after reperfusion onset (posttreatment). A model of ischemic preconditioning was used as the comparator to pretreatment with CSB6B. The results of indicated that posttreatment with CSB6B had profound anti-inflammatory effects that were associated with reduced neurological deficits and a decreased infarct volume. At 24 h, 3 days and 7 days after brain ischemia, CSB6B administration reduced the protein levels of proinflammatory cytokines, such as Il1β, Il6, Il18 and TNFα, in the cerebral cortex and the dorsal striatum. Treatment with CSB6B also limited the scope of microglia and astrocyte activation and the infiltration of immune cells. Taken together, this study shows that compounds such as CSB6B might be promising pharmacological tools; however, further studies on the improvements in the drug-like properties of these compounds must be undertaken.

Therapeutic Potential of Intravenous miR-21 Mimic after Stroke Following STAIR Criteria.

The microRNA-21 (miR-21) levels in the brain are crucial in determining post-stroke brain damage and recovery. The miR-21 exerts neuroprotection by targeting mRNAs that translate proteins that mediate brain damage. We currently determined the efficacy and efficiency of intravenously administered miR-21 mimic after focal cerebral ischemia in mice. Adult male mice were intravenously administered with either control mimic or miR-21 mimic at 5min/2 h after reperfusion following 1h transient middle cerebral artery occlusion to determine the therapeutic window of miR-21 mimic. Adult female, type-2 diabetic male, aged male, and aged female mice were administered with control/miR-21 mimic at 5 min after reperfusion following 35min/1h transient middle cerebral artery occlusion. Early administration of miR-21 mimic significantly reduced brain damage and promoted long-term recovery after stroke. Further, miR-21 mimic is more effective in males than in females subjected to stroke. However, delayed treatment with miR-21 mimic is not efficacious, and type-2 diabetic subjects show no improvement with miR-21 mimic treatment.

Induction of Acute Ischemic Stroke in Mice Using the Distal Middle Artery Occlusion Technique.

Ischemic stroke remains the predominant cause of mortality and functional impairment among the adult populations globally. Only a minority of ischemic stroke patients are eligible to receive intravascular thrombolysis or mechanical thrombectomy therapy within the optimal time window. Among those stroke survivors, around two-thirds suffer neurological dysfunctions over an extended period. Establishing a stable and repeatable experimental ischemic stroke model is extremely significant for further investigating the pathophysiological mechanisms and developing effective therapeutic strategies for ischemic stroke. The middle cerebral artery (MCA) represents the predominant location of ischemic stroke in humans, with the MCA occlusion serving as the frequently employed model of focal cerebral ischemia. In this protocol, we describe the methodology of establishing the distal MCA occlusion (dMCAO) model through transcranial electrocoagulation in C57BL/6 mice. Since the occlusion site is located at the cortical branch of MCA, this model generates a moderate infarcted lesion restricted to the cortex. Neurological behavioral and histopathological characterization have demonstrated visible motor dysfunction, neuron degeneration, and pronounced activation of microglia and astrocytes in this model. Thus, this dMCAO mouse model provides a valuable tool for investigating the ischemiastroke and worth of popularization.

Focal Cerebral Ischemia Induces Global Subacute Changes in the Number of Neuroblasts and Neurons and the Angiogenic Factor Density in Mice.

Background and Objectives: Dissecting the complex pathological cascade of an ischemic stroke in preclinical models is highly warranted to understand the course of this disease in humans. Neurogenesis and angiogenesis are integral for post-stroke recovery, yet it is not clear how these processes are altered months after an ischemic stroke. In this study, we investigated the changes that take place subacutely after focal cerebral ischemia in experimental adult male mice. Materials and Methods: Male 12-week-old C57BL/6 mice underwent a 60 min long fMCAo or sham surgery. Two months after the procedure, we examined the immunohistochemistry to assess the changes in neuroblast (DCX) and differentiated neuron (NeuN) numbers, as well as the density of the pro-angiogenic factor VEGF. Results: We found decreased neuroblast numbers in both brain hemispheres of the fMCAo mice: by more than 85% in the dentate gyrus and by more than 70% in the subventricular zone. No neuroblasts were found in the contralateral hemisphere of the fMCAO mice or the sham controls, but a small population was detected in the ipsilateral ischemic core of the fMCAo mice. Intriguingly, the number of differentiated neurons in the ipsilateral ischemic core was lower by 20% compared to the contralateral hemisphere. VEGF expression was diminished in both brain hemispheres of the fMCAo mice. Conclusions: Our current report shows that focal cerebral ischemia induces changes in neuroblast numbers and the pro-angiogenic factor VEGF in both cerebral hemispheres 2 months after an fMCAo in mice. Our data show that focal cerebral ischemia induces a long-term regenerative response in both brain hemispheres.

Isolation of a novel isoprenylated phenolic compound and neuroprotective evaluation of Dodonaea viscosa extract against cerebral ischaemia–reperfusion injury in rats

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia–reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3ʹ-methyl-2ʹ-butenyl) phenyl 1-O-β-D-apiosyl-(1ʹʹʹ → 6ʹʹ)- β-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4–8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities.

Obesity as a Limiting Factor for Remote Ischemic Postconditioning-Mediated Neuroprotection after Stroke.

Remote ischemic postconditioning (RIPostC) may protect the brain from ischemia/reperfusion (I/R) injury. The association between RIPostC and obesity has not yet been extensively studied. Twelve-week-old male Zucker diabetic fatty (ZDF; n=68) and Zucker diabetic lean (ZDL; n=51) rats were subjected to focal cerebral ischemia for 90 minutes, followed by 24 hours of reperfusion. RIPostC was performed with 5-minute I/R cycles using a tourniquet on the right hind limb. The results showed a negative association between obesity and neurological impairment in ischemic animals. We observed a 70% greater infarct size in ZDF rats compared with their lean counterparts, as evaluated by 2,3,5-triphenyltetrazolium chloride staining. To measure the total fragmented DNA in peripheral lymphocytes, comet assay was performed. Obese rats exhibited higher levels of DNA damage (by approximately 135%) in peripheral blood lymphocytes even before the induction of stroke. RIPostC did not attenuate oxidative stress in the blood in obese rats subjected to ischemia. Focal cerebral ischemia increased core and penumbra tissue glutamate release in the brain and decreased it in the blood of ischemic ZDL rats, and these changes improved following RIPostC treatment. However, changes in blood and tissue glutamate content were not detected in ischemic ZDF rats or after RIPostC intervention. Our findings suggest that obese animals respond more severely to ischemia-reperfusion brain injury. However, obese animals did not achieve neuroprotective benefits of RIPostC treatment.

Se-(Methyl)-selenocysteine ameliorates blood-brain barrier disruption of focal cerebral ischemia mice via ferroptosis inhibition and tight junction upregulation in an Akt/GSK3β-dependent manner.

Ischemic stroke still ranks as the most fatal disease worldwide. Blood-brain barrier (BBB) is a promising therapeutic target for protection. Brain microvascular endothelial cell is a core component of BBB, the barrier function maintenance of which can ameliorate ischemic injury and improve neurological deficit. Se-methyl L-selenocysteine (SeMC) has been shown to exert cardiovascular protection. However, the protection of SeMC against ischemic stroke remains to be elucidated. This research was designed to explore the protection of SeMC from the perspective of BBB protection. To simulate cerebral ischemic injury, C57BL/6J mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R), and bEnd.3 was exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). After the intervention of SeMC, the barrier function and the expression of tight junction and ferroptosis-associated proteins were determined. For mechanism exploration, LY294002 (Akt inhibitor) was introduced both in vivo and in vitro. SeMC lessened the brain infarct volume and attenuated the leakage of BBB in mice. In vitro, SeMC improved cell viability and maintained the barrier function of bEnd.3 cells. The protection of SeMC was accompanied with ferroptosis inhibition and tight junction protein upregulation. Mechanism studies revealed that the effect of SeMC was reversed by LY294002, indicating that the protection of SeMC against ischemic stroke was mediated by the Akt signal pathway. These results suggested that SeMC exerted protection against ischemic stroke, which might be attributed to activating the Akt/GSK3β signaling pathway and increasing the nuclear translocation of Nrf2 and β-catenin, subsequently maintaining the integrity of BBB.

OTUD1 ameliorates cerebral ischemic injury through inhibiting inflammation by disrupting K63-linked deubiquitination of RIP2

BackgroundInflammatory response triggered by innate immunity plays a pivotal element in the progress of ischemic stroke. Receptor-interacting kinase 2 (RIP2) is implicated in maintaining immunity homeostasis and regulating inflammatory response. However, the underlying mechanism of RIP2 in ischemic stroke is still not well understood. Hence, the study investigated the role and the ubiquitination regulatory mechanism of RIP2 in ischemic stroke.MethodsFocal cerebral ischemia was introduced by middle cerebral artery occlusion (MCAO) in wild-type (WT) and OTUD1-deficient (OTUD1−/−) mice, oxygen glucose deprivation and reoxygenation (OGD/R) models in BV2 cells and primary cultured astrocytes were performed for monitoring of experimental stroke. GSK2983559 (GSK559), a RIP2 inhibitor was intraventricularly administered 30 min before MCAO. Mice brain tissues were collected for TTC staining and histopathology. Protein expression of RIP2, OTUD1, p-NF-κB–p65 and IκBα was determined by western blot. Localization of RIP2 and OTUD1 was examined by immunofluorescence. The change of IL-1β, IL-6 and TNF-α was detected by ELISA assay and quantitative real-time polymerase chain reaction. Immunoprecipitation and confocal microscopy were used to study the interaction of RIP2 and OTUD1. The activity of NF-κB was examined by dual-luciferase assay.ResultsOur results showed upregulated protein levels of RIP2 and OTUD1 in microglia and astrocytes in mice subjected to focal cerebral ischemia. Inhibition of RIP2 by GSK559 ameliorated the cerebral ischemic outcome by repressing the NF-κB activity and the inflammatory response. Mechanistically, OTUD1 interacted with RIP2 and sequentially removed the K63-linked polyubiquitin chains of RIP2, thereby inhibiting NF-κB activation. Furthermore, OTUD1 deficiency exacerbated cerebral ischemic injury in response to inflammation induced by RIP2 ubiquitination.ConclusionsThese findings suggested that RIP2 mediated cerebral ischemic lesion via stimulating inflammatory response, and OTUD1 ameliorated brain injury after ischemia through inhibiting RIP2-induced NF-κB activation by specifically cleaving K63-linked ubiquitination of RIP2.

Trilobatin attenuates cerebral ischaemia/reperfusion-induced blood-brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive.

Blood-brain barrier (BBB) breakdown is one of the crucial pathological changes of cerebral ischaemia-reperfusion (I/R) injury. Trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effects against cerebral I/R injury as demonstrated in our previous study. This study was designed to investigate the effect of TLB on BBB disruption after cerebral I/R injury. Rats with focal cerebral ischaemia caused by transient middle cerebral artery occlusion were studied along with brain microvascular endothelial cells and human astrocytes to mimic BBB injury caused by oxygen and glucose deprivation/reoxygenation (OGD/R). The results showed that TLB effectively maintained BBB integrity and inhibited neuronal loss following cerebral I/R challenge. Furthermore, TLB increased tight junction proteins including ZO-1, Occludin and Claudin 5, and decreased the levels of apolipoprotein E (APOE) 4, cyclophilin A (CypA) and phosphorylated nuclear factor kappa B (NF-κB), thereby reducing proinflammatory cytokines. TLB also decreased the Bax/Bcl-2 ratio and cleaved-caspase 3 levels along with a reduced number of apoptotic neurons. Molecular docking and transcriptomics predicted MMP9 as a prominent gene evoked by TLB treatment. The protective effects of TLB on cerebral I/R-induced BBB breakdown was largely abolished by overexpression of MMP9, and the beneficial effects of TLB on OGD/R-induced loss of BBB integrity in human brain microvascular endothelial cells and astrocyte co-cultures was markedly reinforced by knockdown of MMP9. Our findings reveal a novel property of TLB: preventing BBB disruption following cerebral I/R via targeting MMP9 and inhibiting APOE4/CypA/NF-κB axis.

Abstract 262: National Trends of 90‐day Readmission Rates and Etiologies among Diabetics following Transient Ischemic Attack

Introduction Transient Ischemic Attack (TIA) is a common neurologic condition characterized by temporary, focal cerebral ischemia that results in reversible neurological deficits without tissue infarction. Type 2 Diabetes Mellitus (T2DM) is a rapidly growing global health problem with increasing prevalence. Currently, data are lacking regarding the trends of 90‐day readmission rates and etiologies among diabetic patients with TIA. Methods We used the Nationwide Readmission Database (NRD) to identify patients with a primary diagnosis of TIA (ICD‐10 code: G45.9) from 2016‐2019 and secondary diagnosis of T2DM. The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results We identified 426,549 patients who were admitted with a primary diagnosis of TIA between 2016 and 2019. Of those patients, 35.43% (n=273,993) were diabetic and 64.57% (n=151,112) were non‐diabetic. Diabetics were more likely to be younger (70.43 vs 70.71 years, p<0.001) and male (46.62% vs 42.89%, p<0.001) compared to non‐diabetics. All‐cause 90‐day readmission was higher among diabetics compared to non‐diabetics (15.22% vs 12.03%, p<0.001). Nearly half of 90‐day readmissions occurred within 30 days. There was no significant difference in the rate of 90‐day readmission between 2016 and 2019 (13.19% in 2016 and 12.95% in 2019). Among diabetics, readmitted patients were more likely to be older (71.87 vs 70.18 years, p<0.001) and male (47.96% vs 46.38%, p<0.001). Readmitted diabetics had a higher prevalence of valvular disease (10.12% vs 7.94%), chronic renal failure (33.40% vs 23.98%), coronary artery disease (40.20% vs 32.86%), heart failure (23.88% vs 16.07%), atrial fibrillation (24.02% vs 18.88%), dementia (13.87% vs 11.13%), cancer (4.18% vs 2.44%), and prior VTE (5.24% vs 4.44%) (p<0.001 for all). The most common etiologies of 90‐day readmission among diabetics were cardiovascular (28.98%), neurological (12.92%), and infectious (7.72%). Conclusion Diabetics had higher 90‐day readmission following TIA than non‐diabetics. Cardiovascular conditions were the most common cause of readmission followed by neurological and infectious causes. Further studies are needed to improve risk stratification for diabetic patients following TIA and prevent all‐cause readmission.

Conditioned Medium Derived From the Human Amniotic Membrane Prevents Brain Damage Against Cerebral Ischemia/Reperfusion in Subacute, Acute, and Chronic Phases in a Rat Model of Stroke.

Stem cells isolated from the amniotic membrane can produce and release substances that can regenerate damaged tissues and contain proteins and other factors that via numerous major and minor mechanisms lead to increasing angiogenesis and tissue survival. This research was conducted to prove the defensive characteristics of the secretome in the face of temporary focal cerebral ischemia in mouse stroke models. Cerebral ischemia protocol in a specific area was implemented in rats with middle cerebral artery occlusion for 60 minutes and then reperfusion was given for 6, 20, and 30 minutes. Within 30 minutes after the start of reperfusion, conditioned medium derived from the human amniotic membrane (AMSC-CM) was poured into the right ventricle (ICV) at a dose of 0.5 μL. Finally, the volume of the injury, cerebral tissue water, sensorimotor activity, and the strength of the blood-brain barrier integrity were evaluated 24 hours after drug injection. ICV injection of conditioned medium at the start of reperfusion phase considerably decreased the volume of the injury 6, 20, and 30 hours after reperfusion compared to the MCAO-operated group (P<0.01). Cerebral tissue water in the treatment group decreased considerably after the intervention in comparison with the MCAO group in the core and penumbral area not in the subcortical area (P<0.05). Also, the amount of Evans blue infiltration at all times in the core and half-foot area in the AMSC-CM group was significantly reduced in parallel with the MCAO group (P<0.05). Treatment with AMSC-CM during 6-30 h after ischemia-reperfusion insult exerts some beneficial effects against ischemia-reperfusion injury. These findings provide an important vision for more complementary research and treatment of stroke. During ischemia, the brain undergoes a series of harmful pathological events.Mesenchymal stem cells culture medium is called condition medium (CM).CM contains substances that have neuroprotective properties.The use of CM reduces the damage caused by cerebral ischemia. The stem cell culture medium is called condition medium (CM). CM contains substances that have neuroprotective properties. This study aims to investigate the effect of CM on injuries caused by stroke. After causing a stroke in rats by closing the artery, the CM was injected into the injury site. The results showed that CM reduced the severity of the injury.

Correction: Estimation of Chaos and Coherence in Frontoparietal, Occipital and Temporal Lobes at Pre, Post and During Focal Cerebral Ischemia

Correction: Estimation of Chaos and Coherence in Frontoparietal, Occipital and Temporal Lobes at Pre, Post and During Focal Cerebral Ischemia

Neuroprotective Effects of Water Extract from Brown Algae Petalonia binghamiae in an Experimental Model of Focal Cerebral Ischemia In Vitro and In Vivo.

Focal cerebral ischemia (fCI) can result in brain injury and sensorimotor deficits. Brown algae are currently garnering scientific attention as potential therapeutic candidates for fCI. This study investigated the therapeutic effects of the hot water extract of Petalonia binghamiae (wPB), a brown alga, in in vitro and in vivo models of fCI. The neuroprotective efficacy of wPB was evaluated in an in vitro excitotoxicity model established using HT-22 cells challenged with glutamate. Afterward, C57/BL6 mice were administered wPB for 7 days (10 or 100 mg/kg, intragastric) and subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) operation, which was used as an in vivo fCI model. wPB co-incubation significantly inhibited cell death, oxidative stress, and apoptosis, as well as stimulated the expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, and the nuclear translocation of its upstream regulator, nuclear factor erythroid 2-related factor 2 (Nrf2) in HT-22 cells challenged with glutamate-induced excitotoxicity. Pretreatment with either dose of wPB significantly attenuated infarction volume, neuronal death, and sensorimotor deficits in an in vivo fCI model. Furthermore, the attenuation of oxidative stress and apoptosis in the ischemic lesion accompanied the wPB-associated protection. This study suggests that wPB can counteract fCI via an antioxidative effect, upregulating the Nrf2/HO-1 pathway.

Electroacupuncture at GB20 improves cognitive ability and synaptic plasticity via the CaM-CaMKII-CREB signaling pathway following cerebral ischemia-reperfusion injury in rats.

This study aimed to investigate the effects of electroacupuncture (EA) on cognitive recovery and synaptic remodeling in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion and explore the possible mechanism. Focal cerebral ischemia was modeled in healthy adult Sprague-Dawley rats by MCAO. The MCAO rats were classified into four groups: sham, MCAO, MCAO + GB20 (receiving EA at GB20) and MCAO + NA (receiving EA at a "non-acupoint" location not corresponding to any traditional acupuncture point location about 10 mm above the iliac crest). Neurological deficit scores and behavior were assessed before and during the treatment. After intervention for 7 days, the hippocampus was dissected to analyze growth-associated protein (GAP)-43, synaptophysin (SYN) and postsynaptic density protein (PSD)-95 expression levels by Western blotting. Bioinformatic analysis and primary hippocampal neurons with calcium-voltage gated channel subunit alpha 1B (CACNA1B) gene overexpression were used to screen the target genes for EA against MCAO. Significant amelioration of neurological deficits and learning/memory were found in MCAO + GB20 rats compared with MCAO or MCAO + NA rats. Protein levels of GAP-43, SYN and PSD-95 were significantly improved in MCAO + GB20-treated rats together with an increase in the number of synapses in the hippocampal CA1 region. CACNA1B appeared to be a target gene of EA in MCAO. There were increased mRNA levels of CACNA1B, calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase type II (CaMKII) and cyclic adenosine monophosphate response element binding (CREB) and increased phosphorylation of CaM, CaMKII and CREB in the hippocampal region in MCAO + GB20 versus MCAO and MCAO + NA groups. CACNA1B overexpression modulated expression of the CaM-CaMKII-CREB axis. EA treatment at GB20 may ameliorate the negative effects of MCAO on cognitive function in rats by enhancing synaptic plasticity. EA treatment at GB20 may exert this neuroprotective effect by regulating the CACNA1B-CaM-CaMKII-CREB axis.

Intravenous human dental pulp-derived mesenchymal stem cell therapy for ischemic stroke in rats: an analysis of functional and ischemic brain areas outcomes

Cellular therapies have been implicated in treating and rehabilitating ischemic stroke (IS), involving the basic experimental and preclinical areas. Using mesenchymal stem cells (MSC) derived from human dental pulp has shown promising results in animal models, but still with mechanisms and consequences that are not entirely clear. The study aims to evaluate the effects of intravenous MSC on rats with IS regarding neurological function and histological areas of ischemia. Thirty-two male Wistar rats underwent temporary occlusion of the middle cerebral artery (TOMCA) for 60 minutes and were divided into two groups of 16 animals each. One group received dental pulp MSC intravenously, and another received saline 2 hours after TOMCA. The animals were then evaluated using the neurological functionality scales for 15 days, and at the end of the experiment period, the histological areas of cerebral ischemia were analysed. All animals presented ischemic areas and neurological deficits compatible with IS. There was partial recovery of the functionality scores over the evaluation period, and all animals presented focal cerebral ischemia measured by histological analysis; however, there was no statistical difference between the groups. The TOMCA model was effective in reproducing IS. Although we found no difference between treatment groups, our results were useful in showing the pattern of neurological recovery presented by animals treated with dental pulp MSC and the need to extend the evaluation time for a longer period and use more sensitive functional tests. The results add valuable data for improving research with dental pulp MSC in the murine model of IS.