Focal Ischemia Research Articles

Diurnal Differences in Immune Response in Brain, Blood and Spleen After Focal Cerebral Ischemia in Mice.

The immune response to acute cerebral ischemia is a major factor in stroke pathobiology. Circadian biology modulates some aspects of immune response. The goal of this study is to compare key parameters of immune response during the active/awake phase versus inactive/sleep phase in a mouse model of transient focal cerebral ischemia. Mice were housed in normal or reversed light cycle rooms for 3 weeks, and then they were blindly subjected to transient focal cerebral ischemia. Flow cytometry was used to examine immune responses in blood, spleen, and brain at 3 days after ischemic onset. In blood, there were higher levels of circulating T cells in mice subjected to focal ischemia during zeitgeber time (ZT)1-3 (inactive or sleep phase) versus ZT13-15 mice (active or awake phase). In the spleen, organ weight and immune cell numbers were lower in ZT1-3 versus ZT13-15 mice. Consistent with these results, there was an increased infiltration of activated T cells into brain at ZT1-3 compared with ZT13-15. This proof-of-concept study indicates that there are significant diurnal effects on the immune response after focal cerebral ischemia in mice. Hence, therapeutic strategies focused on immune targets should be reassessed to account for the effects of diurnal rhythms and circadian biology in nocturnal rodent models of stroke.

Cannabidiol Exerts a Neuroprotective and Glia-Balancing Effect in the Subacute Phase of Stroke.

Pharmacological agents limiting secondary tissue loss and improving functional outcomes after stroke are still limited. Cannabidiol (CBD), the major non-psychoactive component of Cannabis sativa, has been proposed as a neuroprotective agent against experimental cerebral ischemia. The effects of CBD mostly relate to the modulation of neuroinflammation, including glial activation. To investigate the effects of CBD on glial cells after focal ischemia in vivo, we performed time-lapse imaging of microglia and astroglial Ca2+ signaling in the somatosensory cortex in the subacute phase of stroke by in vivo two-photon laser-scanning microscopy using transgenic mice with microglial EGFP expression and astrocyte-specific expression of the genetically encoded Ca2+ sensor GCaMP3. CBD (10 mg/kg, intraperitoneally) prevented ischemia-induced neurological impairment, reducing the neurological deficit score from 2.0 ± 1.2 to 0.8 ± 0.8, and protected against neurodegeneration, as shown by the reduction (more than 70%) in Fluoro-Jade C staining (18.8 ± 7.5 to 5.3 ± 0.3). CBD reduced ischemia-induced microglial activation assessed by changes in soma area and total branch length, and exerted a balancing effect on astroglial Ca2+ signals. Our findings indicate that the neuroprotective effects of CBD may occur in the subacute phase of ischemia, and reinforce its strong anti-inflammatory property. Nevertheless, its mechanism of action on glial cells still requires further studies.

MMP-12 knockdown prevents secondary brain damage after ischemic stroke in mice

We previously reported that increased expression of matrix metalloproteinase-12 (MMP-12) mediates blood-brain barrier disruption via tight junction protein degradation after focal cerebral ischemia in rats. Currently, we evaluated whether MMP-12 knockdown protects the post-stroke mouse brain and promotes better functional recovery. Adult male mice were injected with negative siRNA or MMP-12 siRNA (intravenous) at 5 min of reperfusion following 1 h transient middle cerebral artery occlusion. MMP-12 knockdown significantly reduced the post-ischemic infarct volume and improved motor and cognitive functional recovery. Mechanistically, MMP-12 knockdown ameliorated degradation of tight junction proteins zonula occludens-1, claudin-5, and occludin after focal ischemia. MMP-12 knockdown also decreased the expression of inflammatory mediators, including monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and the expression of apoptosis marker cleaved caspase-3 after ischemia. Overall, the present study indicates that MMP-12 promotes secondary brain damage after stroke and hence is a promising stroke therapeutic target.

Evaluation of hemostasis clinical and laboratory indicators of patients with stroke and coronavirus infection (COVID-19) on the basis of a multidisciplinary hospital in the period of its conversion to an infectious diseases hospital

Introduction. The COVID-19 impact on hemostasis of stroke survivors with community-acquired pneumonia is an urgent problem. The aim of the study is to analyze the features of clinical and laboratory parameters in cerebral stroke combined with community-acquired pneumonia caused by the SARS-Co-V-2 virus. Materials and methods. The instrumental and laboratory examination results of 88 patients aged 73.0 (12.3) years in the acute period of stroke with community-acquired viral pneumonia symptoms were analyzed. The present study included 39.8 % (n=53) male and 60.2 % female (n=35) with duration of diagnosed infectious disease less than 7 days. The symptoms of cerebral stroke were compared with the results of laboratory testing of the hemostasis system, lipid metabolism, and the activity of the systemic inflammatory response. The severity of lung tissue damage and the outcomes of the diagnosed changes were assessed. Results. All patients had mild or moderate COVID-19. In 87.5 % (n=77) cases unspecified (40.2 %, n=31), cardioembolic (36.4 %, n=28), lacunar (3.9 %, n=3) and atherothrombotic (19.5 %, n=15) ischemic stroke subtype was diagnosed. Focal ischemia lesion in the left middle cerebral artery (LMCA) territory was detected in 45.6 % (n=35), in the right middle cerebral artery (RMCA) territory in 41.6 % (n=32). Manifestations of hemorrhagic stroke were noted in 12.5 % (n=11) with signs of parenchymal hemorrhage in 54.5 % (n=6), ventricular hemorrhage in 27.3 % (n=3), subarachnoid hemorrhages were noted in 18.2 % (n=2). The indicators of the coagulation system in terms of the number of platelets corresponded to 251.3 (90.7); the APTT value was in the range of 29.2 (26.7 33.0) (s); the INR parameter was 1.16 (1.05 1.25); the value of prothrombin ( %) corresponded to the value of 85.9(23.4). Conclusion. We do not observe the great disorders of haemostasis in the most acute period of the stroke. When combined with COVID-19 the most common stroke is ischemic stroke. The stroke survivors with the community-acquired pneumonia caused by SARS-CoV-2 laboratory tests show that increase of inflammatory markers are above the reference range.

PRESENTATION OF ACUTE CEREBROVASCULAR ACCIDENT IN A YOUNG ADULT WITH THROMBOTIC THROMBOCYTOPENIA PURPURA (TTP)

PRESENTATION OF ACUTE CEREBROVASCULAR ACCIDENT IN A YOUNG ADULT WITH THROMBOTIC THROMBOCYTOPENIA PURPURA (TTP)

Laser Speckle Flowmetry for the Prognostic Estimation Study of Permanent Focal Ischemia in Mice

The distal middle cerebral artery occlusion (dMCAO) model that mainly targets the cortex and causes low mortality is developed for the study of permanent focal ischemia, and it is highly appropriate for the study in the aged population. The two most common methods used to establish dMCAO models are dMCAO alone and dMCAO plus ipsilateral common carotid artery occlusion (CCAO). Up to now, studies on the prognosis of the two types of dMCAO models and the accuracy of cerebral blood flow (CBF) in predicting prognosis have not yet been reported. In the present study, we established permanent focal ischemia models in two groups of aged mice by dMCAO alone or by dMCAO plus ipsilateral common carotid artery occlusion (CCAO). CBF was evaluated by laser speckle flowmetry (LSF) before and after surgery. Cerebral infarction was assessed by TTC staining at day 2 after surgery and MAP2 staining at day 21 after surgery. In addition, behavioral outcomes were evaluated using the modified Garcia scoring system, adhesive removal test, and foot-fault test. Our results showed that compared with those in the dMCAO alone group, the mice in the dMCAO plus CCAO group had a larger cerebral infarct size and more severe neurological deficits. According to the results of the correlation analysis, the area of the ischemic core region on CBF imaging in the dMCAO group was helpful in predicting the infarct volume. In addition, the total CBF of the ischemic area in the dMCAO plus CCAO group showed a significant correlation with Garcia scores 3 days after surgery, but there was no significant correlation of CBF imaging with the foot-fault test 7 days after surgery. These results suggest that the total CBF of the ischemic area might be helpful to predict the severity of neurological damage at the acute stage.

Transient Intraluminal Filament Middle Cerebral Artery Occlusion Stroke Model in Rats: A Step-by-Step Guide and Technical Considerations

Stroke is a leading cause of disability and mortality worldwide. Related research, although already providing significant insights regarding the underlying pathophysiology and potential treatment strategies, has been far from conclusive. Stroke models have been proved of extreme significance for laboratories around the world. In the present report, we have described in detail the most popular to date focal stroke model, the transient intraluminal filament middle cerebral artery occlusion (tifMCAO) model in rats. This model reliably mimics stroke in humans and also approximates endovascular thrombectomy. The tifMCAO model was performed using Wistar rats weighing 300-400 g. We have described the surgical technique in a stepwise manner, with figures and/or high-definition video provided for each step. We have also introduced the use of complete arteriotomy of the external carotid artery stump during the procedure. We performed tifMCAO in 65 rats (male and female) involved in various experimental protocols. Although the initial mortality was 48%, practice reduced the rate to 10%. The mean procedural time was 53 minutes (range, 38-85 minutes). In a group of 8 rats ischemia was confirmed in 7 of them, with the stroke induction rate being 87.5%. The tifMCAO stroke model in rats is the most often used experimental model of focal ischemia because of its clinical relevance. We revisited the procedure and divided it, for instructional purposes, into 15 consecutive and distinct steps.

Ischemic stroke in a pediatric patient: complication of the course of COVID-19 (clinical case and literature review)

Recently, there is a growing number of publications about the complicated course of the COVID-19 in children. The literature describes only a few cases of acute cerebrovascular diseases. In the case described in this paper, an 11‑year-old boy presented with COVID-19 complicated by an ischemic stroke. Moderate ischemic stroke (pedNIHSS 14 points) occurred on the 7th day after infection with the SARS-CoV-2 and the background of the multisystem inflammatory syndrome. It has started with the left hemiplegia, hemianesthesia, central-type facial moderate palsy, and pseudobulbar palsy. Focal brain ischemia in the right hemisphere brain and occlusion of the right middle cerebral artery was confirmed by neuroimaging data. The treatment observed regression of neurological symptoms: there were minimal movements in his left arm and leg, facial muscles, also improved gulping and speech. After 1.5 months, the stroke was provided clinical examination: no markers predisposing to hypercoagulability or a prothrombotic state, as well as markers of systemic diseases. According to neuroimaging data, was occurred recanalization of occluded middle cerebral artery, was postischemic changes. This case shows the possibility of stroke against the background of COVID-19 in children without somatic problems and makes the doctor more vigilant during the treatment of COVID-19.

Propofol ameliorates ischemic brain injury by blocking TLR4 pathway in mice.

Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 ± 2.7 vs 15.7 ± 2.0 mm3 at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 ± 0.23 vs 1.00 ± 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 ± 3.1 vs 25.1 ± 4.7 cells/0.1 mm2). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.

Diagnostic value of diffusion tensor imaging in patients with clinical signs of cervical spondylotic myelopathy.

The aim of this study was to assess the diagnostic value of diffusion tensor imaging (DTI) in patients with symptoms of cervical myelopathy. Detailed goals included determining the diagnostic effectiveness of quantitative parameters, i.e. fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in the diagnosis of cervical myelopathy, and the correlation between these parameters and clinical symptoms. The demonstration of an ischaemic focus in the spinal cord by standard magnetic resonance imaging (MRI) methods is associated with already accomplished spinal cord damage, and of course limited treatment options. Therefore, finding a new examination protocol that allows early diagnosis of myelopathic focus, before the onset of full neurological symptoms, has become a priority in the diagnosis and treatment of spine diseases. Such an examination increases the chances of correctly qualifying the patient for conservative vs. surgical treatment. Between 2013 and 2017, 128 adults with clinical signs of cervical myelopathy were examined, and were divided into four symptomatic subgroups. A control group consisted of 37 healthy volunteers. DTI values were measured at the level of C2/C3, and at the most severe stenosis of the spine. In patients with cervical spondylotic myelopathy (CSM), the ADC values were significantly higher (p < 0.001), and FA values were significantly lower (p < 0.001), than in healthy volunteers at the stenotic level. There were significant differences in DTI parameters between the clinical subgroups (p < 0.001). Changes in DTI parameters indicate a microstructural disorder of the core which is not visible in a structural MRI. FA and ADC values measured at the level of the most severe stenosis of the spinal canal allow the differentiation of patients with myelopathy of varying degrees of clinical severity. Extending standard MRI to include assessment of FA and ADC may be helpful in deciding treatment modalities (conservative vs. surgical) for patients with visible canal stenosis without full neurological symptoms. This may be useful in selecting patients for urgent rehabilitative treatment. This study is a starting point for further research, i.e. an evaluation of the extent of FA and ADC lesion withdrawal after surgical treatment.

Influence of a new stimulator of soluble guanylate cyclase on platelet aggregation and vascular endothelial function in experimental ischemic stroke against the background of arterial hypertension

Background. Correction of endothelial dysfunction during arterial hypertension (AH) is an important measure in preventing cerebrovascular stroke. Drugs activating soluble guanylate cyclase (sGC) and 3’,5’-guanosine monophosphate (cGMP) production independently of nitric oxide (NO) were shown to be therapeutically useful in reducing the risk of stroke. The present work aims to study the antiaggregant and endothelium-protective activity of a new sGC stimulator, an indolinone derivative (2-[2-[(5RS)-5-(hydroxymethyl)-3-methyl-1,3-oxazolidine-2- yliden]-2-cyanoethylidene]-1H-indole-3(2H)-one (codename — GRS) in a model of ischemic stroke with AH. Prior studies have shown that GRS compound inhibits platelet aggregation, lowers blood pressure (BP) in spontaneouslyhypertensive SHR rats, prevents vascular occlusion in models of arterial and venous thrombosis. Antiplatelet drug clopidogrel, a P2Y12 receptor inhibitor, included in the standard of care for secondary prevention of ischemic stroke, was used as the reference drug.Objective. To assess the antiaggregant and endothelium-protective activity of a new indolinone derivative GRS, an sGC stimulator, compared to clopidogrel in a model of ischemic stroke concomitant with high arterial BP in spontaneously-hypertensive SHR rats.Design and methods. Focal brain ischemia/reperfusion was modelled in spontaneously-hypertensive SHR rats (n = 78). GRS in 10 mg/kg dose and clopidogrel in 10 mg/kg dose were administered orally once daily 3 days before modelling ischemia/reperfusion and for 5 days afterwards. Platelet aggregation and functioning of vascular endothelium were monitored.Results. Focal brain ischemia/reperfusion in SHR rats resulted in increased platelet aggregation and the development of endothelial dysfunction and disruption of vasodilatory function of endothelium. GRS compound and clopidogrel in repeated administration have prevented an increase in platelet aggregation (p &lt; 0,05), GRS compound also alleviated endothelial dysfunction (p &lt; 0,05).Conclusions. The indolinone derivative GRS, an sGC stimulator, inhibits increased platelet aggregation and prevents endothelial dysfunction in rats after focal brain ischemia/ reperfusion; the endothelium-protective effects of GRS aren’t related to its antiaggregant activity.

What affects the neurovisualisational detection of ischemic stroke?

Introduction. The incidence of stroke is 2.5–3 cases per 1 000 population per year, mortality – 1 case per 1 000 population per year. According to various data, up to 20% of computed tomography (CT) scans performed on the first day do not reveal signs of an ischemic focus.Aim of the study. To assess the detectability of acute ischemia foci using CT, depending on the location of the foci, the timing of neuroimaging, the severity of stroke, and other indicators.Material and methods. We analyzed 100 cases of acute cerebrovascular accident (ACV) by ischemic type. The timing of the CT scan, glucose level, coagulogram parameters, NIHSS scores at admission, focus localization, the presence of atherosclerosis of the arteries of the head, and atrial fibrillation were taken into account. Patients were divided into two groups depending on the fact of detection of the focus during the primary tomographic examination. Repeated neuroimaging (magnetic resonance imaging) was performed in 54 patients.Results. In the “CT-negative” group, stem strokes predominated (p = 0.01), patients were younger (р = 0.038), and there were significantly more women than men (р = 0.00006). An increase in glucose over 8 mmol/l, on the contrary, was more often detected in the “CT-positive” group (14 cases in “CT-positive” against 5 cases in “CT-negative” group, p = 0.022). NIHSS scores ≥ 5 were found in 24 patients (47%) in the “CT-positive” group and in 13 patients (26.5%) in the “CT-negative” group (p = 0.034).Conclusions. Cases of stroke that are not detected on CT scan upon admission to the hospital are more common among women, with stem localization, are associated with low NIHSS scores. High glucose levels at admission is associated with the detection of ischemic foci during the initial CT examination.

Reversible cerebral vasoconstriction syndrome: review of neuroimaging findings.

Reversible cerebral vasoconstriction syndrome (RCVS) is a group of disorders characterized by segmental narrowing and dilatation of medium-to-large cerebral arteries, clinically presenting with recurrent episodes of sudden-onset thunderclap headaches, with or without focal neurological deficits. Cerebral vasoconstriction is typically reversible, with spontaneous resolution within 3 months. Although the syndrome has generally a benign course, patients with neurological deficits may experience worse outcome. The main imaging finding is segmental constriction of intracranial arteries, which can be associated with subarachnoid hemorrhage and/or ischemic foci. Other possible findings are intracranial hemorrhage, subdural bleeding and cerebral edema. The latter may have a pattern which can resemble that of posterior reversible encephalopathy syndrome, a condition that can overlap with RCVS. New imaging techniques, such as vessel wall imaging and arterial spin labeling, are proving useful in RCVS and are giving new insights into the pathophysiology of this condition. In this paper, we aim to review neuroimaging findings of RCVS.

Hemophilia A developing cerebral infarction after surgical treatment of giant hemophilic pseudotumor: a case report

BackgroundCerebral infarction (CI) is an unusual complication in patients with bleeding disorders. To our knowledge, this is the first case of postoperative internal border-zone infarction (I-BZI) from Hemophilia A.Case presentationWe present a case of Hemophilia A developing I-BZI, after surgical treatment of giant hemophilic pseudotumor. A 36-year-old man was introduced from other hospital by Hemophilia with giant hemophilic pseudotumor in his left thigh. Patient and his relatives did not have a history of thrombophilia. After excluding the relevant surgical contraindications, we performed the operation of pseudotumor resection. Prior to surgery, blood tests revealed hemoglobin of 137 g/L. FVIII activity was 1.5%. Activated partial thromboplastin time (APTT) was 71.50 s and D-dimer was 3.33 mg/L FEU. Immediately before surgery, the patient received an intravenous infusion of FVIII products (Xyntha®) at a dose of 3500 IU for his body weight of 80 kg. Post-operative day two (POD2), patient developed vomiting, decreased response, and dysarthria. Hemoglobin was 54 g/L with blood pressure of 110/70 mmHg. Magnetic resonance imaging of the brain showed there were multiple acute cerebral infarctions in bilateral lateral ventricles (internal border zone) and multiple ischemic foci in the white matter areas and basal ganglia of the bilateral cerebral hemispheres. This case suggested that acute severe anemia can be one of the causes of I-BZI.ConclusionsFor the treatment of I-BZI caused by acute anemia from Hemophilia A, volume expansion, red blood cell supplement and continuous improvement of coagulation with suitable dose of factor VIII (FVIII) should be considered to improve prognosis.

A worsened prognosis for patients after a stroke with newly diagnosed atrial fibrillation compared to having a preexisting arrhythmia.

IntroductionAtrial fibrillation (AF) is a major cause of the ischemic stroke. Patients with undiagnosed AF lack the stroke prevention provided by oral anticoagulants. The aim of this study was to compare the in-hospital mortality rate between ischemic stroke patients diagnosed with AF de novo against ischemic stroke patients diagnosed with AF prior to hospitalization for stroke.Material and methodsWe identified patients admitted to the Neurology Center during the years 2013-2014 with acute ischemic stroke and AF. We analyzed in-hospital outcomes in patients with newly diagnosed AF and those with known AF. The study endpoint was death during hospitalization.ResultsThe study included 2,000 patients with acute ischemic stroke out of which 579 patients (29%) were diagnosed with AF. AF was newly diagnosed in 123 patients (21.2%) (new-AF group), while 456 patients (78.8%) had a history of AF (previous-AF group). Mean National Institutes of Health Stroke Scale (NIHSS) score at admission was 7.2 points in the new-AF group and 3.7 in previous-AF group (P&lt;0.001). In-hospital death was more common in new-AF group (13 patients, 10.6%) than in previous-AF group (16 patients, 3.5%) (P=0.003). In multivariate analysis, the NIHSS score at admission in new-AF group was associated with higher mortality, while in previous-AF group, the NIHSS score at admission and multiple ischemic foci were risk factors of in-hospital mortality.ConclusionsNewly diagnosed AF in ischemic stroke patients significantly worsens prognosis compared to patients previously diagnosed with AF. Early detection of latent AF and subsequent use of anticoagulation is important in preventing severe stroke.

Dose-Dependent Effects of Intravenous Mesenchymal Stem Cell Transplantation in Rats with Acute Focal Cerebral Ischemia.

Intravenous transplantation of mesenchymal stem (stromal) cells (MSC) is a promising approach to the treatment of ischemic stroke. In the published reports of the already completed preclinical and clinical studies the dosages of transplanted MSC greatly vary. However, the optimal dosage has not been determined. The dose-dependent effect of intravenous MSC transplantation was studied, in rats with experimental cerebral infarction. To this end, 5×105 and 2×106 MSC were intravenously administered 24 h after modeling of acute focal ischemia followed by complex assessment of the therapeutic efficacy over 60 days. The rate and degree of the recovery of neurological functions in rats increased with increasing the dose of injected cells, which confirms the dose-dependent effect of intravenous MSC transplantation.

Establishment of the reproducible branch retinal artery occlusion mouse model and intravital longitudinal imaging of the retinal CX3CR1-GFP+ cells after spontaneous arterial recanalization.

Animal models of retinal artery occlusion (RAO) have been widely used in many studies. However, most of these studies prefer using a central retinal artery occlusion (CRAO) which is a typical global ischemia model of the retina, due to the technical limitation of producing single vessel targeted modeling with real-time imaging. A focal ischemia model, such as branch retinal artery occlusion (BRAO), is also needed for explaining interactions, including the immunological reaction between the ischemic retina and adjacent healthy retina. Accordingly, a relevant model for clinical RAO patients has been demanded to understand the pathophysiology of the RAO disease. Herein, we establish a convenient BRAO mouse model to research the focal reaction of the retina. As a photo-thrombotic agent, Rose bengal was intravenously injected into 7 week-old transgenic mice (CX3CR1-GFP) for making embolism occlusion, which causes pathology similarly to clinical cases. In an optimized condition, a 561 nm laser (13.1 mw) was projected to a targeted vessel to induce photo-thrombosis for 27 s by custom-built retinal confocal microscopy. Compared to previous BRAO models, the procedures of thrombosis generation were naturally and minimal invasively generated with real-time retinal imaging. In addition, by utilizing the self-remission characteristics of Rose bengal thrombus, a reflow of the BRAO with immunological reactions of the CX3CR1-GFP+ inflammatory cells such as the retinal microglia and monocytes was monitored and analyzed. In this models, reperfusion began on day 3 after modeling. Simultaneously, the activation of CX3CR1-GFP+ inflammatory cells, including the increase of activation marker and morphologic change, was confirmed by immunohistochemical (IHC) staining and quantitative real-time PCR. CD86 and Nox2 were prominently expressed on day 3 after the modeling. At day 7, blood flow was almost restored in the large vessels. CX3CR1-GFP+ populations in both superficial and deep layers of the retina also increased around even in the BRAO peri-ischemic area. In summary, this study successfully establishes a reproducible BRAO modeling method with convenient capabilities of easily controllable time points and selection of a specific single vessel. It can be a useful tool to analyze the behavior of inflammatory cell after spontaneous arterial recanalization in BRAO and further investigate the pathophysiology of BRAO.

MiR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice.

Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.

Pakshaghata (Hemiparesis) management - Cerebral Vascular Event (CVE) Through Panchakarma, Shamana treatment and Physiotherapy - A Case Report

Background: Cerebrovascular complaint is the third most common cause of death in high-income countries after cancers and ischemic heart complaint and the most common cause of severe physical disability. In India, studies estimate that prevalence of stroke varies from 116 to 163 per population. According to ICMR, stroke is the 4th leading cause of death and the 5th leading cause of disability acclimated lifetime (DALY). Stroke is the most common clinical incarnation of Cerebrovascularcomplaint and results in occurrences of brain dysfunction due to focal ischemia or Haemorrhage. Subarachnoid Haemorrhage (SAH) and cerebral venous thrombosis (CVT) will be bandied independently since their pathophysiology, clinical instantiations, and operation are distinct from a stroke. Material &amp;Methods: An 83 years old male K/ H/ O HTNwas diagnosed with an AvaranajanyaPakshaghata with a clinical point. There was a loss of function in the left lower and upper limbs. He was not able to stand without proper support. He was having weakness of the left upper and lower limbs. He was treated with Shaman Chikitsa followed by ShodhanChikitsa as SarvanagaAbhyanga, Marsha Nasya, ShashtiShaliPindaSwedana, Shirodhara, AnuvasanaBasti, and NiruhaBasti for 15 days. Result: The patient was assessed with gold standard stroke parameters, i.e., Barthel Index &amp; National Institute of Health Stroke Scale (NIH-SS), in which scores were turned from 15 &amp; 21 to 65 &amp; 9, respectively. Moreover, significant changes and improvements were observed in clinical features OF Pakshaghata before and after treatment. Conclusion: In this case, there is an involvement of Aama as an Avarana on Vata, which is vitiating the VataRoga and causes Pakshaghat.This first line of Treatment was under the elimination of the Aama involvement from Chief Complaints. It was done by Deepana- Pachana medicine as Shaman Chikitsa. After that, the ShodhanChikitsa was started by gaining the Nirama condition of Doshas. A significant improvement was observed by combining the Shaman and ShodhanChikitsa strategically.

Acute iron overload aggravates blood-brainbarrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia.

Hemorrhagic transformation (HT) has been reported to be associated with a poor prognosis after acute ischemic stroke. Blood-brain barrier (BBB) damage is considered as the major pathophysiologic mechanism of HT. Our aim was to investigate the role of acute iron overload in BBB damage and HT after transient focal ischemia in rats with hyperglycemia. Transient middle cerebral artery occlusion (MCAO) was induced in rats with hyperglycemia. Animals were assigned to four groups: Sham, Vehicle, Iron overload and Iron chelator treatment groups. Brain samples were collected at 24 h after surgery to quantify the amount of hemorrhage, determine extravasation of Evans blue and detect the levels of following proteins: ferritin, matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), Occludin and Claudin-5 by western blot analysis and immunohistochemistry. Compared to the Vehicle group, the Iron overload group had a significantly higher amount of hemorrhage and more extravasation of Evans blue. The Iron overload group had lower levels of ZO-1, Occludin and Claudin-5 and higher levels of ferritin and MMP-9 than the Vehicle group. Administering iron chelator reduced the extension of hemorrhage and extravasation of Evans blue, reversed the MCAO-induced reduction of ZO-1, Occludin and Claudin-5 and decreased the levels of ferritin and MMP-9. Our results suggest that acute iron overload aggravates BBB damage and HT after transient ischemia in rats with hyperglycemia, which provides basic evidence for iron overload as a potential factor associated with BBB damage and HT in ischemic stroke patients when accompanied with hyperglycemia.