Middle Cerebral Research Articles

Resting-State Functional Magnetic Resonance Imaging Reveals the Effects of rTMS on Neural Activity and Brain Connectivity After Experimental Stroke.

Limited understanding of neurobiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) prevents us from choosing optimal therapeutic regimen for patients to improve therapeutic efficiency. Resting-state functional magnetic resonance imaging (rs-fMRI) has been demonstrated to obtain comparable functional readouts across species. Intermittent and continuous theta burst stimulation were used to stimulate ipsilesional and contralesional hemisphere, respectively, during the subacute phase after stroke. We used a rat middle cerebral artery occlusion stroke model. The amplitude of low-frequency fluctuations and functional connectivity analyses of rs-fMRI were chosen to detect neuron activity and functional connectivity. The expression of neuron activation marker c-Fos and axonal plasticity marker GAP43 was examined by an immunochemistry method to corroborate the results of rs-fMRI. iTBS altered the long-term neuronal activity in bilateral sensorimotor cortex, whereas cTBS influenced immediate neuronal activity of bilateral sensorimotor cortex. In addition, cTBS enhanced interhemispheric and intrahemisheric functional connectivity in contralesional hemisphere, accompanied by axonal and dendritic remodeling in the perilesional cortical areas and contralesional homologous areas after large stroke. rTMS exerted complex effects on brain structural and functional connectivity in addition to affecting cortical excitability. cTBS promoted the compensatory effect of contralesional hemisphere after stroke with large lesions.

Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke.

The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4- triazole derivative (SYS18) had obviously neuroprotection by anti- oxidative stress on rat middle cerebral artery occlusion (MCAO) model. In this study, we continue to investigate its neuroprotection by anti-inflammatory effects and protecting BBB integrity in AIS. First, its effect on acute inflammation was evaluated by the mice model of increased peritoneal capillary permeability. Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood-brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase- 9 (MMP- 9) and claudin- 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone. Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.

Long-Term Neurologic Outcomes in Pediatric Arterial Ischemic Stroke: The Impact of Age and Lesion Location.

The impact of age-at-stroke on outcome following pediatric arterial ischemic stroke remains controversial. We studied the interaction of age-at-stroke and infarct location and extent with long-term neurological outcomes. We conducted a longitudinal prospective outcome study of children with acute pediatric arterial ischemic stroke diagnosed from 1996 to 2016 at the Hospital for Sick Children, Toronto, Canada. Pediatric Stroke Outcome Measure scores were dichotomized as normal or abnormal (ie, mild, moderate, or severe). Outcomes were analyzed by age-at-stroke (newborn: birth to 28 days; early childhood: 29 days to 5 years; middle/late childhood: >5-18 years), and infarct location, based on each of the following: model 1: circulation (anterior/posterior); model 2: cortical versus subcortical involvement; and model 3: specific arterial territory, including infarct extent (small [<50% arterial territory] or large [≥50%]). Univariable and multivariable logistic regression models were fitted. Among 285 children, the outcome at median 6.1 years was 43.5% abnormal. Controlling for infarct location, increasing age-at-stroke was associated with increasing abnormal outcome. Model 1 demonstrated that, compared with neonates, abnormal outcomes were increased in early childhood (adjusted odds ratio [aOR], 2.91 [95% CI, 1.24-7.05]) and more so in middle/late childhood (aOR, 4.46 [95% CI, 1.71-12.13]). Outcomes were worse for combined locations, including anterior+posterior (model 1: aOR, 15.4 [95% CI, 4.49-64.63]) and cortical+subcortical (model 2: aOR, 10.7 [95% CI, 3.88-32.74]). Abnormal outcomes were also increased for anterior circulation (model 1: aOR, 14.91 [95% CI, 5.29-54.21]) and subcortical locations (model 2: aOR, 4.36 [95% CI, 1.37-14.95]). Among individual arterial territories, outcomes were best for superior division middle cerebral artery (100% normal) and worst for lateral lenticulostriate artery infarcts (47.4% abnormal; model 3: aOR, 14.2 [95% CI, 3.5-67.6]). Among survivors of pediatric stroke, abnormal long-term neurological outcome is increased with increasing age-at-stroke, supporting enhanced plasticity after focal injury to the newborn brain compared with older pediatric ages.

Loganin attenuates the inflammation, oxidative stress, and apoptosis through the JAK2/STAT3 pathway in cerebral ischemia-reperfusion injury

BackgroundLoganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, has been reported to have anti-inflammatory and antioxidant activity. Nevertheless, the potential role and molecular mechanism of loganin in cerebral ischemia-reperfusion (I/R) injury are not well-understood. The purpose of the study was to explore the functional role of loganin in the inflammation, oxidative stress, and apoptosis in cerebral I/R injury in rats Materials and methodsFollowing middle cerebral artery occlusion (MCAO), 80 mg/kg of loganin was intragastrically administered for 7 consecutive days. Neuromotor function scores were performed 24 h after the last administration, and the cerebral infarction volume was determined by TTC straining. The expressions of IL-6, IL-1β, and TNF-α in the brain tissues of MCAO rats were detected by ELISA assay. The activities of ROS, SOD, and MDA were measured by ELISA assay as well. Cell apoptosis were was tested by TUNEL straining. Western blot assay was applied for measuring the protein levels ResultsWe observed that the expressions of IL-6, IL-1β, and TNF-α were amplitude markedly elevated in the rats following MCAO. Treatment with loganin obviously reduced these expressions in the brain tissues of MCAO rats. ELISA assay showed that ROS generation and MDA activity were increased in MCAO group and it was decreased after treatment with loganin. However, loganin increased the SOD activity, which was reduced by MCAO operation. Moreover, loganin promoted neurological function improvement and inhibited cell apoptosis in the rats after MCAO. Mechanically, loganin triggered JAK2/STAT3 phosphorylation in the rats following MCAO, and activation of JAK2/STAT3 pathway rescued the inhibition effects of loganin on the inflammation, oxidative stress, and apoptosis ConclusionsThese results provide evidence that loganin may alleviate the inflammation, oxidative stress, and apoptosis through the JAK2/STAT3 pathway in MCAO rats.

Rational development of fingolimod nano-embedded microparticles as nose-to-brain neuroprotective therapy for ischemic stroke.

Ischemic stroke is one of the major diseases causing varying degrees of dysfunction and disability worldwide. The current management of ischemic stroke poses significant challenges due to short therapeutic windows and limited efficacy, highlighting the pressing need for novel neuroprotective treatment strategies. Previous studies have shown that fingolimod (FIN) is a promising neuroprotective drug. Here, we report the rational development of FIN nano-embedded nasal powders using full factorial design experiments, aiming to provide rapid neuroprotection after ischemic stroke. Flash nanoprecipitation was employed to produce FIN nanosuspensions with the aid of polyvinylpyrrolidone and cholesterol as stabilizers. The optimized nanosuspension (particle size = 134.0 ± 0.6nm, PDI = 0.179 ± 0.021, physical stability = 72 ± 0h, and encapsulation efficiency of FIN = 90.67 ± 0.08%) was subsequently spray-dried into a dry powder, which exhibited excellent redispersibility (RdI = 1.09 ± 0.04) and satisfactory drug deposition in the olfactory region using a customized 3D-printed nasal cast (45.4%) and an Alberta Idealized Nasal Inlet model (8.6%) at 15L/min. The safety of the optimized FIN nano-embedded dry powder was confirmed in cytotoxicity studies with nasal (RPMI 2650 and Calu-3 cells) and brain related cells (SH-SY5Y and PC 12 cells), while the neuroprotective effects were demonstrated by observed behavioral improvements and reduced cerebral infarct size in a middle cerebral artery occlusion mouse stroke model. The neuroprotective effect was further evidenced by increased expression of anti-apoptotic protein BCL-2 and decreased expression of pro-apoptotic proteins CC3 and BAX in brain peri-infarct tissues. Our findings highlight the potential of nasal delivery of FIN nano-embedded dry powder as a rapid neuroprotective treatment strategy for acute ischemic stroke.

Gnetupendin A protects against ischemic stroke through activating the PI3K/AKT/mTOR-dependent autophagy pathway

BackgroundAutophagy has been recently emerged as a prominent factor in the pathogenesis of ischemic stroke (IS) and is increasingly being considered as a potential therapeutic target for IS. Gnetum parvifolium has been identified as a potential therapeutic agent for inflammatory diseases such as rheumatism and traumatic injuries. However, the pharmacological effects of Gnetupindin A (GA), a stilbene compound isolated from Gnetum parvifolium, have not been fully elucidated until now. ObjectiveHere we identified the therapeutic potential of GA for IS, deeply exploring the possible mechanisms related to its regulation of autophagy. MethodsThe mouse model of middle cerebral artery occlusion-reperfusion (MCAO/R) and the oxygen-glucose deprivation reperfusion (OGD/R)-exposed cells served as models to study the protection of GA against IS. The adeno-associated virus (AAV) encoding shAtg5, in conjunction with autophagy inhibitor 3-Methyladenine (3-MA) were utilized to explore the role of GA in regulating autophagy following IS. Molecular docking, CETSA, and DARTS were used to identify the specific therapeutic target of GA. PI3K inhibitor LY294002 was employed to test the participation of PI3K in GA-mediated autophagy and neuroprotective effects following IS. ResultsOur findings revealed that treatment with GA significantly alleviated the brain infract volume, edema, improved neurological deficits and attenuated apoptosis. Mechanistically, we found that GA promoted autophagic flow both in vivo and in vitro after IS. Notably, neural-targeted knockdown of Atg5 abolished the neuroprotective effects mediated by GA. Inhibition of autophagy using 3-MA blocked the attenuation on apoptosis induced by GA. Moreover, molecular docking, CETSA, and DARTS analysis demonstrated that GA specifically targeted PI3K and further inhibited the activation of PI3K/AKT/mTOR signaling pathway. LY294002, which inhibits PI3K, reversed GA-induced autophagy and neuroprotective effects on OGD/R-treated cells. ConclusionWe demonstrated, for the first time, that GA protects against IS through promoting the PI3K/AKT/mTOR-dependent autophagy pathway. Our findings provide a novel mechanistic insight into the anti-IS effect of GA in regulating autophagy.

Scalp acupuncture alleviates remote hippocampal damage in MCAO rats by inhibiting neuroinflammation: A TMT-based proteomics analysis

While mounting evidence suggests that scalp acupuncture (SA) may be effective in alleviating neurological deficits in patients with acute ischemic stroke (IS), its effect on remote hippocampal damage in acute IS and the underlying mechanisms remain elusive. Thus, proteomics analysis was conducted to identify potential targets of SA therapy in acute IS. SA significantly reduced cerebral infarct volume and attenuated neuronal damage in the ischemic penumbra and hippocampus, as well as alleviated neurological deficits in rats with middle cerebral artery occlusion (MCAO). Moreover, 74 upregulated and 50 downregulated proteins were identified in the MCAO group compared to the sham group, whilst 52 up-regulated and 50 down-regulated proteins were identified in the SA group compared to the MCAO group. Bioinformatics analysis indicated that SA may exert neuroprotective effects by modulating the acute inflammatory response and microglial activation. Additionally, SA down-regulated the expression levels of Iba-1, TNF-α, IL-1β, and IL-6, while up-regulating those of IL-4 and IL-10. Likewise, it downregulated the expression levels of three key proteins identified via proteomics analysis (Kng1, Brd9, and Magl) that may mediate the anti-inflammatory effects of SA. Overall, these results indicate that SA attenuates neuronal damage in the hippocampus and ischemic penumbra and ameliorates neurological deficits. Proteomic analysis suggested that this effect is related to the modulation of the acute inflammatory response. SA attenuated remote hippocampal damage after IS by inhibiting microglia activation and neuroinflammation. Lastly, Kng1, Brd9, and Magl were identified as potential targets that mediate the anti-inflammatory effects of SA.

Galangin Regulates Astrocyte Phenotypes to Ameliorate Cerebral Ischemia-reperfusion Injury by Inhibiting the RhoA/ROCK/LIMK Pathway.

This study aimed to explore whether Galangin (Gal) could improve cerebral Ischemia- reperfusion (I/R) injury by regulating astrocytes, and clarify its potential molecular mechanism. An I/R injury model of rats was established using the Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) method, followed by the administration of Gal (25, 50, 100 mg/kg) via gavage for 14 consecutive days. Besides, astrocytes were isolated from the rats to construct an Oxygen-Glucose Deprivation/Re-oxygenation (OGD/R) cell model, with treatments of Gal or the Ras homolog gene family member A (RhoA)/Rho-associated Coiled-coil containing protein Kinase (ROCK) inhibitor Y-27632. Subsequently, the severity of nerve injury was assessed using the modified Neurological Severity Score (mNSS) test; behavioral disorders in I/R rats were observed through the open field and ladder-climbing tests. Pathological damages and neuron survival in the peri-infarct zone were examined by hematoxylin and eosin staining and NeuN staining, respectively. Additionally, immunofluorescence staining was employed to determine astrocyte polarization and TUNEL staining was carried out to measure the level of cell apoptosis; also, western blot was performed to detect the expression of proteins related to the RhoA/ROCK/LIM domain Kinase (LIMK) pathway. Gal significantly ameliorated the neurological and motor dysfunctions caused by I/R in rats, reduced pathological damage in the peri-infarct zone, and promoted neuronal survival. Additionally, Gal increased the number of A2 astrocytes, while it decreased the number of A1 astrocytes. In vitro experiments revealed that the effect of Gal was consistent with that of Y-27632. Additionally, Gal significantly enhanced the survival of OGD/R cells, increased the number of A2 astrocytes, and inhibited the expression of proteins associated with the RhoA/ROCK pathway. Gal could reduce the level of apoptosis, promote the polarization of A2 astrocytes, and improve cerebral I/R injury, and its mechanism may be related to the inhibition of the RhoA/ROCK pathway.

Circle of Willis and Its Anatomical Relevance

The Circle of Willis is an arterial network located at the base of the brain, formed by the interconnection of the anterior, middle, and posterior cerebral arteries, along with the anterior and posterior communicating arteries. It connects the internal carotid arteries to the vertebral arteries, allowing the distribution of cerebral blood flow. Its significance lies in its ability to offer an alternative pathway in cases of arterial obstruction, helping to prevent cerebral ischemia. However, anatomical variations of this structure are common, and only 20% to 25% of the population has a "complete" or symmetrical configuration. Such variations can influence the risk of cerebrovascular diseases, such as stroke, as they may compromise the efficiency of the compensatory mechanism. These anatomical variations have a direct impact on the diagnosis and treatment of neurological conditions. The integrity of the Circle of Willis can influence the severity of symptoms in cases of ischemic strokes, as well as affect aneurysm formation and its clinical implications. Advances in imaging techniques, such as CT angiography and magnetic resonance imaging, have enabled more accurate diagnoses and the development of more effective treatments for conditions associated with the Circle of Willis, making its anatomical understanding essential for the prevention and management of cerebrovascular diseases.

VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives neuroinflammation in mouse ischemic stroke.

Astrocyte-derived IL-3 activates the corresponding receptor IL-3Rα in microglia. This cross-talk between astrocytes and microglia ameliorates the pathology of Alzheimer's disease in mice. In this study we investigated the role of IL-3/IL-3Rα cross-talk and its regulatory mechanisms in ischemic stroke. Ischemic stroke was induced in mice by intraluminal occlusion of the right middle cerebral artery (MCA) for 60 min followed by reperfusion (I/R). Human astrocytes or microglia subjected to oxygen-glucose deprivation and reoxygenation (OGD/Re) were used as in vitro models of brain ischemia. We showed that both I/R and OGD/Re significantly induced decreases in astrocytic IL-3 and microglial IL-3Rα protein levels, accompanied by pro-inflammatory activation of A1-type astrocytes and M1-type microglia. Importantly, astrocyte-derived VEGFD acting on VEGFR3 of astrocytes and microglia contributed to the cross-talk dysfunction and pro-inflammatory activation of the two glial cells, thereby mediating neuronal cell damage. By using metabolomics and multiple biochemical approaches, we demonstrated that IL-3 supplementation to microglia reversed OGD/Re-induced lipid metabolic reprogramming evidenced by upregulated expression of CPT1A, a rate-limiting enzyme for the mitochondrial β-oxidation, and increased levels of glycerophospholipids, the major components of cellular membranes, causing reduced accumulation of lipid droplets, thus reduced pro-inflammatory activation and necrosis, as well as increased phagocytosis of microglia. Notably, exogenous IL-3 and the VEGFR antagonist axitinib reestablished the cross-talk of IL-3/IL-3Rα, improving microglial lipid metabolic levels via upregulation of CPT1A, restoring microglial phagocytotic function and attenuating microglial pro-inflammatory activation, ultimately contributing to brain recovery from I/R insult. Our results demonstrate that VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives pro-inflammatory activation, causing lipid metabolic reprogramming of microglia. These insights suggest VEGFR3 antagonism or restoring IL-3 levels as a potential therapeutic strategy for ischemic stroke.

Early Resolution of Abnormal Vascular Networks After Superficial Temporal Artery to Middle Cerebral Artery (STA-MCA) Bypass Surgery for Twig-Like Middle Cerebral Artery With Intracerebral Hemorrhage: A Case Report

Early Resolution of Abnormal Vascular Networks After Superficial Temporal Artery to Middle Cerebral Artery (STA-MCA) Bypass Surgery for Twig-Like Middle Cerebral Artery With Intracerebral Hemorrhage: A Case Report

Quantifying neurovascular coupling through a concurrent assessment of arterial, capillary, and neuronal activation in humans: A multimodal EEG-fNIRS-TCD investigation

BackgroundThis study explored a novel multimodal neuroimaging approach to assess neurovascular coupling (NVC) in humans using electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and transcranial Doppler ultrasound (TCD). MethodsFifteen participants (nine females; age 19–32) completed concurrent EEG-fNIRS-TCD imaging during motor (finger tapping) and visual (“Where's Waldo?”) tasks, with synchronized monitoring of blood pressure, capnography, and heart rate. fNIRS assessed microvascular oxygenation within the frontal, motor, parietal, and occipital cortices, while the middle and posterior cerebral arteries (MCA/PCA) were insonated using TCD. A 16-channel EEG set-up was placed according to the 10–20 system. Wilcoxon signed-rank tests were used to compare physiological responses between the active and resting phases of the tasks, while cross-correlations with zero legs compared cerebral and systemic hemodynamic responses across both tasks. ResultsTime-frequency analysis demonstrated a reduction in alpha and low beta band power in electrodes C3/C4 during finger tapping (p<0.045) and all electrodes during the Waldo task (all p<0.001). During Waldo, cross-correlation analysis demonstrated the change in oxygenated hemoglobin and cerebral blood velocity had a moderate-to-strong negative correlation with systemic physiological influences, highlighting the measured change resulted from neuronal input. Deoxygenated hemoglobin displayed the greatest negative cross-correlation with the MCA/PCA within the motor cortices and visual during the motor and visual tasks, respectively (range:0.54, -0.82). ConclusionsThis investigation demonstrated the feasibility of the proposed EEG-fNIRS-TCD response to comprehensively assess the NVC response within human, specifically quantifying the real-time temporal synchrony between neuronal activation (EEG), microvascular oxygenation changes (fNIRS), and conduit artery velocity alterations (TCD).

Mild hypercapnia before reperfusion reduces ischemia-reperfusion injury in hyperacute ischemic stroke rat model.

Endovascular thrombectomy has a recanalization rate over 80%; however, approximately 50% of ischemic stroke patients still experience dependency or mortality. Recently, clinical trials demonstrated the benefits of administering neuroprotective agents prior to endovascular thrombectomy. Additionally, recent studies showed neuroprotective effects of mild hypercapnia in patients resuscitated after cardiac arrest. However, its efficacy in ischemic stroke remains unclear. We aimed to investigate whether carbon dioxide (CO2) per-conditioning has neuroprotective effects in rat models with middle cerebral artery occlusion (MCAO). Rat models received intermittent inhalation of mixed gas during the MCAO period. After surgery, behavioral assessments, infarct size measurement, immunohistochemistry, and western blot analysis were performed. We found CO2 per-conditioning reduced infarct size and neurological deficit. The number of 8-hydroxy-2-deoxyguanosine (8-OHdG) positive cells and matrix metalloproteinase 9 (MMP-9)/platelet derived growth factor receptor beta (PDGFRβ) double positive cells were significantly decreased after CO2 per-conditioning. The expressions of tight junction protein and pericytes survival were preserved. This study underscores mild hypercapnia before reperfusion not only reduces neurologic deficit and infarct size, but also maintains the integrity of the blood-brain barrier and neurovascular unit, alongside mitigating oxidative stress in hyperacute stroke rat models. Therapeutic mild hypercapnia before reperfusion is promising and requires further clinical application.

Edaravone Dexborneol protects against blood-brain barrier disruption following cerebral ischemia/reperfusion by upregulating pericyte coverage via vitronectin-integrin and PDGFB/PDGFR-β signaling

BackgroundRecent advancements in brain cytoprotection therapies following cerebral ischemia-reperfusion (I/R) injury have become an emerging interest. Pericytes were vulnerable during the early stages of ischemia. This study aims to explore the protective effects of Edaravone borneol (Eda.B) on pericyte loss, as well as and the underlying mechanisms, given its potential in alleviating I/R injury. Methods: The rat transient middle cerebral artery occlusion (tMCAO) model was established. Rats were randomly divided into Sham group (Sham, n = 24), tMCAO group (tMCAO, n = 24), Edaravone group (Eda, n = 24), Dexborneol group (Dexborneol, n = 24), and Eda.B group (Eda.B, n = 24). Neurological function recovery, infarct volume, and blood-brain barrier (BBB) disruption were assessed using Zea-Longa scoring, TTC staining, and Evans Blue extravasation, respectively. Alterations in Basement membrane (BM) and pericyte coverage were assessed by transmission electron microscopy (TEM). The expression levels of pericyte marker NG2 and PDGFR-β in the ischemic region, as well as BBB transcellular transport-related proteins vitronectin (VTN), α5 and PDGFB were detected by western blotting. Furthermore, a specific inhibitor of PDGFB, MOR8457, was employed (Eda.B + MOR8457, n = 8) to explore the protective effects of Eda.B on pericyte injury via PDGFB/PDGFR-β. ResultsEda.B significantly reduced cerebral infarct volume and promoted neurological function recovery in comparison to the tMCAO, Eda and Dexborneol groups. Additionally, Eda.B significantly ameliorated BBB leakage, mitigated the decrease in pericyte coverage, and reduced vesicle density in endothelial cells and BM thickness following I/R. Mechanically, Eda.B inhibited the downregulation of NG2, PDGFB/PDGFR-β, VTN, while preventing upregulation of α5 protein expression in tMCAO rats. Blocking PDGFB with MOR8457 demonstrated that Eda.B improved pericyte loss and BBB permeability by activating PDGFB/PDGFR-β signaling. ConclusionsWe elucidated that vitronectin-integrin and PDGFB/PDGFR-β signaling contributed to Eda.B's protective effects against pericyte loss and BBB permeability following I/R injury, unraveling new insights into mechanisms of pericyte as a promising therapeutic target.

Fat mass and obesity-associated protein alleviates cerebral ischemia/reperfusion injury by inhibiting ferroptosis via miR-320-3p/SLC7A11 axis

Fat mass and obesity-associated protein (FTO) is a demethylase and has recently been found to have a protective effect in acute ischemic stroke (AIS), but the underlying mechanism is unclear to a large extent. New studies have found that the expression of certain miRNAs may be affected by N6-methyladenosine (m6A) levels. Here, using high-throughput sequencing and quantitative polymerase chain reaction, we found miR-320-3p was significantly up-regulated in AIS patients. miR-320-3p aggravated the neurobehavioral manifestation, infarct volume and histopathology of middle cerebral artery occlusion/reperfusion model mice. Mechanically, miR-320-3p binds to the 3′ untranslated region of solute carrier family 7 member 11 (SLC7A11) mRNA, promoting oxidative stress and ferroptosis induced by oxygen-glucose deprivation/reoxygenation in neurons. FTO inhibited the m6A methylation of the primary transcript pri-miR-320 and the maturation of miR-320-3p, thus having a protective effect on cerebral ischemia/reperfusion injury after AIS. Clinically, we also confirmed the down-regulation of FTO and SLC7A11 mRNA in the peripheral blood of AIS patients and their correlation with the expression of miR-320-3p. Our study found that FTO inhibits ferroptosis through miR-320-3p/SLC7A11 axis in an m6A-dependent manner, and thus has a protective effect on cerebral ischemic reperfusion injury. Our results provided a promising therapeutic target of cerebral ischemia/reperfusion injury after AIS.

Optimization of image shoot timing for cerebral veins 3D-digital subtraction angiography by interventional angiography systems

Abstract3D-digital subtraction angiography (3D-DSA) is essential for understanding the anatomical structure of cerebral veins, crucial in brain tumor surgery. 3D-DSA produces three-dimensional images of veins by adjusting the X-ray delay time after contrast agent injection, but the delineation of veins varies with the delay in X-ray timing. Our study aimed to refine the delay time using time-enhancement curve (TEC) analysis from 2D-DSA conducted before 3D-DSA imaging. We retrospectively reviewed 26 meningioma patients who underwent cerebral angiography from March 2020 to August 2021. Using 2D-DSA, we analyzed arterial and venous TECs to determine the contrast agent’s peak time and estimated the optimal imaging timing. Cases performed near this optimal time were in Group A, and others in Group B, with cerebral venous pixel values compared between them. TEC analysis identified peak times: internal carotid artery: 2.8 ± 0.7 s, middle cerebral artery (M4): 4.1 ± 0.9 s, superior sagittal sinus: 8.3 ± 1.1 s, sigmoid sinus: 9.5 ± 1.3 s, and venous structures near tumors: 7.3 ± 1.0 s. We observed several veins peaking immediately after arterial contrast passage, suggesting the optimal X-ray delay should incorporate the arterial contrast agent’s transit time. Statistical analysis revealed that Group A, with imaging timed to reflect the contrast agent transit time, demonstrated significantly better contrast effects than Group B. The X-ray delay time for 3D-DSA imaging of cerebral veins can be optimized in angiography systems by incorporating the contrast agent transit time, calculated from TEC analysis of cerebral 2D-DSA images.

Endovascular therapy in patients with acute intracranial non-terminal internal carotid artery occlusion (ICA-I).

Acute intracranial occlusion of the internal carotid artery (ICA) can be distinguished into (a) occlusion of the terminal ICA, involving the proximal segments of the middle or anterior cerebral artery (ICA-L/-T) and (b) non-terminal intracranial occlusions of the ICA with patent circle of Willis (ICA-I). While patients with ICA-L/-T occlusion were included in all randomized controlled trials on endovascular therapy (EVT) in anterior large vessel occlusion, data on EVT in ICA-I occlusion is scarce. We thus aimed to evaluate effectiveness and safety of EVT in ICA-I occlusions in comparison to ICA-L/-T occlusions. A large international multicentre cohort was searched for patients with intracranial ICA occlusion treated with EVT between 2014 and 2023. Patients were stratified by ICA occlusion pattern, differentiating ICA-I and ICA-L/-T occlusions. Baseline factors, technical (modified thrombolysis in cerebral infarction (mTICI) scale) and functional outcomes (modified Rankin scale [mRS] at 3 months) as well as rates of (symptomatic) intracranial hemorrhage ([s]ICH) were analyzed. Of 13,453 patients, 1825 (13.6%) had isolated ICA occlusion. ICA-occlusion pattern was ICA-I in 559 (4.2%) and ICA-L/-T in 1266 (9.4%) patients. Age (years: 74 vs 73), sex (female: 45.8% vs 49.0%) and pre-stroke functional independency (pre-mRS ⩽ 2: 89.9% vs 92.2%) did not differ between the groups. Stroke severity was lower in ICA-I patients (NIHSS at admission: 14 [7-19] vs 17 [13-21] points). EVT was similarly successful with respect to technical (mTICI2b/3: 76.1% (ICA-I) vs 76.6% (ICA-L/-T); aOR 1.01 [0.76-1.35]) and functional outcome (mRS ordinal shift cOR 1.01 [0.83-1.23] in adjusted analyses. Rates of ICH (18.9% vs 34.5%; aOR 0.47 [0.36-0.62] and sICH (4.7% vs 7.3%; aOR 0.58 [0.35-0.97] were lower in ICA-I patients. EVT might be performed safely and similarly successful in patients with ICA-I occlusions as in patients with ICA-L/-T occlusions.

Transforming Stroke Recovery: The Bobath Concept in a Case Study of Middle Cerebral Artery Infarction

Stroke remains a major cause of long-term disability, necessitating effective rehabilitation strategies. This case study examines the rehabilitation of a 57-year-old male patient recovering from a middle cerebral artery (MCA) infarction, utilising the Model of Bobath Clinical Practice (MBCP). The patient underwent interventions based on the Bobath concept, focusing on selective activation of trunk muscles, core engagement, and pelvic alignment to enhance postural control. Assessments revealed significant improvements in both sitting and standing postures, with reductions in compensatory fixation strategies. The targeted therapeutic exercises facilitated better trunk control and lower limb weight-bearing, resulting in overall enhanced stability. The findings underscore the importance of individualised approaches in stroke rehabilitation aligned with Bobath principles. While the outcomes are promising, further research is needed to confirm the effectiveness of the MBCP model across varied patient populations. This study highlights the potential of the Bobath Concept in improving functional recovery and quality of life for stroke survivors.

Cardiac autonomic changes after stroke

Abstract Introduction There is a highly complex and clinically important relationship between the cardiac and the nervous system, called the heart-brain axis [1]. Therefore, acute brain damage may lead to alterations in cardiac function due to changes in the autonomic nervous system[2,3]. Novel computerised biosignal analysis techniques and advanced biosignal assessment could provide a valuable tool to sensitively analyse cardiac autonomic function (CAF). CAF can be characterized by two complementary digital biomarkers, periodic repolariation dynamics (PRD) and deceleration capacity (DC). The aim of this study was to determine CAF by means of PRD and DC in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and to analyze them according to their relationship with specific cardiac (high-sensitive Troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP)) and stroke (location, type, severity) characteristics. Methoden / Methods Between February 22, 2021, and May 5, 2023, 282 patients after an AIS or TIA were enrolled in the study. During the inpatient stay, all relevant parameters were recorded and stored in a database. To assess CAF, a 30-minute biosignal measurement was performed with a high resolution (1kHz) electrocardiogram (ECG). Cardiac autonomic biomarkers, PRD and DC, were calculated semiautomatically afterwards from patients. Results Fifteen ECGs were excluded due to poor recording quality. Consequently, data from 261 AIS and 21 TIA patients were analyzed. A total of 105 patients (37.2 %) had pathological PRD (≥ 5.75 deg2) and/or DC (≤ 2.5 ms), 78 patients (27.7 %) had pathological PRD, and 57 patients (20.2 %) had pathological DC. The median PRD was 3.13 deg2 and the median DC was 5.30 ms (see Figure). There were no significant differences in the distribution of PRD and DC between male and female patients (PRD p = 0.38, DC p = 0.30), and between AIS and TIA patients (PRD p = 0.13, DC p = 0.66). Patients with middle cerebral artery (MCA) infarction had significantly higher median PRD values (3.56 deg2 [IQR 1.51 - 6.59 ] vs. 2.81 deg2 [IQR 1.15 - 5.99], p = 0.047) and lower median DC values (4.66 ms [IQR 2.65 – 7.76] vs. 6.11 ms [IQR 3.15 – 10.61], p = 0.011) than patients with stroke located in another cerebral regions (see Figure). Patients with pathological PRD or DC had significantly higher hsTnT (13.50 ng/l [IQR 9.7 – 24.1] vs. 11.05 ng/l [ IQR 7.13 – 16.23], p &amp;lt; 0.001) and NT-pro BNP (269.00 ng/l [IQR 117.50 – 687.00] vs. 125.50 ng/l [IQR 57.00 – 288.25], p &amp;lt; 0.001) values. Conclusions The study showed that a considerable proportion, more than one third of all patients, had evidence of cardiac autonomic dysfunction after acute cerebral ischaemia. Of particular interest, PRD was higher and DC was lower in patients with MCA ischaemia, reflecting a potentially higher cardiac risk profile. Cardiac autonomic dysfunction was also associated with increased hsTnT and NT-proBNP levels.