Focal Ischemia Research Articles

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

Intravenous Regeneration-associated Cell Transplantation Enhances Tissue Recovery in Mice with Acute Ischemic Stroke.

Previously, we reported that transplantation of regeneration-associated cells (RACs) via the ipsilateral external carotid artery reduced stroke volume in mice with permanent occlusion of the middle cerebral artery (MCA). However, intracarotid arterial transplantation is invasive and requires skill, and severe complications may occur, such as thromboembolism, infection, and decreased cerebral blood flow. This study aimed to investigate the efficacy of intravenous injection of RACs in reducing stroke volume and increasing anti-inflammatory and angiogenic factors in mice with focal cerebral ischemia. Mice with occluded MCAs received intravenous injections of phosphate-buffered saline (PBS) (control), low-dose RACs, or high-dose RACs. The proximal part of the left MCA was occluded to induce permanent focal ischemia. After 3 days, we administered PBS or low-dose (1 × 104 /50 µL) or high-dose RACs (1 × 105 /50 µL) through the tail vein and assessed the infarct volume on day 7. High-dose RACs significantly decreased infarct volume compared to PBS, whereas low-dose RACs showed no effect. The number of interleukin-10 (IL-10)-positive and vascular endothelial growth factor (VEGF)-positive cells in the peri-infarct area on day 7 was significantly higher in mice treated with low-dose and high-dose RACs than in the PBS control group. Intravenous injection of RACs can reduce ischemic stroke volume; however, a higher dose of RACs is required than the dose used in intraarterial transplantation. By assessing IL-10 and VEGF expression, the study sheds light on the underlying mechanisms of RAC therapy, revealing its potential anti-inflammatory and angiogenic properties in the treatment of cerebral ischemia.

Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura

Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction.

Cerebral net uptake of lactate contributes to neurological injury after experimental cardiac arrest in rabbits

During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Experimental study. Experimental laboratory. Male New-Zealand rabbits. Animals were surgically instrumented and randomly divided into five groups receiving short infusion duration of either lactate or pyruvate or a pre-cardiac arrest infusion of oxamate (an inhibitor of the lactate dehydrogenase) or injection of fluorocitrate (an inhibitor of astrocytic tricarboxylic acid), or Saline (lactate, pyruvate, Oxa, FC and Control groups, respectively). After randomization, animals were submitted to 10 min of ventricular fibrillation and subsequent resuscitation. All animals were then either followed during 4 h, for the evaluation of the cerebral net uptake and concentrations of metabolites by microdialysis (n = 6 in each experimental group, n = 12 in control group), or during 48 h for the evaluation of their neurological outcome (n = 7 in each groups and n = 14 in control group). Cardiac arrest was associated with a dramatic increase in cerebral net uptake of lactate during 120 min after resuscitation, which was increased by lactate or pyruvate administration. This was associated with an increase in the mean neurological dysfunction score (66.7 ± 4.7, 79.0 ± 4.5 vs 57.7 ± 1.5 in Lactate, Pyruvate and Control group respectively) at 48 h after cardiac arrest. Oxamate and FC administration were associated with a lower lactate cerebral uptake after cardiac arrest and with an improvement of the neurological recovery (28.85 ± 9.4, 23.86 ± 6.2 vs 57.7 ± 1.5 in Oxa, FC and Control group respectively). After cardiac arrest, immediate isotonic lactate or pyruvate administration is deleterious. Pre-cardiac arrest LDH inhibition was potently neuroprotective in this setting.

Neuro- and vasoprotective potential of neuropeptide Y Y2 receptor agonist, NPY13-36, against transient focal cerebral ischemia in spontaneously hypertensive rats

Numerous in vitro and in vivo experimental studies indicate that neuropeptide Y Y2 receptors (Y2R) are potential targets for neuroprotective therapy, including neuroprotection against ischemic stroke in healthy rats. Since stroke in humans is typically associated with comorbidities and long-term hypertension is the most common comorbidity leading to stroke, this study aimed to assess the neuroprotective potential of the Y2R agonist NPY13–36 in the rats with essential hypertension (SHR) subjected to 90 min middle cerebral artery suture occlusion with subsequent reperfusion (MCAOR). The cerebrocortical microflow in the ischemic focus and penumbra was continuously monitored with a Laser-Doppler flowmeter. NPY13–36 (10 μg/6 μl physiological saline solution) was administered intracerebroventricularly (i.c.v.) during ischemia or early reperfusion. The infarct area (triphenyltetrazolium chloride staining), behavioral tests (gait, mobility, and sensorimotor functions), and the response of the cerebrocortical microcirculation in the penumbra to hypercapnia and to the inhibition of the synthesis of nitric oxide were studied. Our results demonstrate that administration of NPY13-36 reduces the size of the infarct, improves motor functions, and restores microcirculatory response to the blockade of nitric oxide synthase when administered during reperfusion. The novelty of this study is a finding of the vasoprotective effect of NPY13-36 in brain ischemia/reperfusion. Moreover, this study provides evidence of the beneficial effects of NPY13-36 in animals with essential hypertension and indicates that Y2R ligands may be promising candidates for treating the ischemic brain in the case of this disease.

The impact of rehabilitation on the recovery of executive functions in stroke patients with different location of the ischemic focus.

Cognitive dysfunction is part of the clinical picture of stroke. Most of the executive dysfunctions are diagnosed in the early stage of rehabilitation, a few weeks after the vascular incident. Coexistence of executive dysfunctions with other disorders in stroke patients may hinder patient's functions, slow down the rehabilitation process, and disrupt self-awareness, interpersonal communication, and professional activity in everyday life. Ninety patients after ischemic stroke were examined (right hemisphere stroke: N = 33, left hemisphere stroke: N = 57). The study group (N = 45) consisted of patients rehabilitated in the Department of Rehabilitation and Physical Medicine of the University Teaching Hospital of the Military Medical Academy in Lodz, Łódź, Poland, in whom a comprehensive neurorehabilitation program was implemented, consisting of motor and neuropsychological rehabilitation. The control group (N = 45) consisted of patients awaiting admission to the department, who were covered by comprehensive environmental rehabilitation including exercise therapy and neuropsychological therapy. Executive function was measured with 3 popular diagnostic tools: the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT part A, TMT part B), and the letter test and category test with the Verbal Fluency Test (VFT). The tests were carried out twice: the first time before the start of rehabilitation and 5 weeks later after its completion. Although patients with right-hemispheric stroke showed better improvement in executive functions, stroke location did not prove to have significant impact on how effective the rehabilitation was. Right hemisphere stroke patients showed greater improvement in restoring executive functions after rehabilitation compared to left hemisphere stroke patients. The location of the stroke did not significantly correlate with the efficiency of the rehabilitation setting. Int J Occup Med Environ Health. 2024;37(4).

Trombóza mozkových splavů jako primomanifestace adenomu příštítného tělíska

Primary hyperparathyroidism (HPPT) is a generalized disorder of calcium-phosphate metabolism resulting from long-term secretion of parathyroid hormone (PTH). The most common cause of PTH overproduction is an adenoma of one or more parathyroid glands. Cerebral venous sinus thrombosis accounts for about 1–2% of cerebral events and its consequence can be focal ischemia with intracerebral hemorrhage. In this article, we describe a unique case report of a patient who was urgently admitted for the progression of a sudden speech disorder and progressive impairment of consciousness on the basis of thrombosis in the cerebral sinuses and intracerebral hemorrhage. Secondary findings at the initial diagnostic process were hypophosphatemia and hypercalcemia with parathyroid hormone elevation.

Overview of mechanism of electroacupuncture pretreatment for prevention and treatment of cardiovascular and cerebrovascular diseases.

Cardio-cerebrovascular disease (CCVD) is a serious threat to huma strategy to prevent the occurrence and development of disease by giving electroacupuncture intervention before the disease occurs. EAP has been shown in many preclinical studies to relieve ischemic symptoms and improve damage from ischemia-reperfusion, with no comprehensive review of its mechanisms in cardiovascular disease yet. In this paper, we first systematically discussed the meridian and acupoint selection law of EAP for CCVD and focused on the progress of the mechanism of action of EAP for the prevention and treatment of CCVD. As a result, in preclinical studies, AMI and MCAO models are commonly used to simulate ischemic injury in CCVD, while MIRI and CI/RI models are used to simulate reperfusion injury caused by blood flow recovery after focal tissue ischemia. According to the meridian matching rules of EAP for CCVD, PC6 in the pericardial meridian is the most commonly used acupoint in cardiovascular diseases, while GV20 in the Du meridian is the most commonly used acupoint in cerebrovascular diseases. In terms of intervention parameters, EAP intervention generally lasts for 30 min, with acupuncture depths mostly between 1.5 and 5 mm, stimulation intensities mostly at 1 mA, and commonly used frequencies being low frequencies. In terms of molecular mechanisms, the key pathways of EAP in preventing and treating cardiovascular and cerebrovascular diseases are partially similar. EAP can play a protective role in cardiovascular and cerebrovascular diseases by promoting autophagy, regulating Ca2+ overload, and promoting vascular regeneration through anti-inflammatory reactions, antioxidant stress, and anti-apoptosis. Of course, both pathways involved have their corresponding specificities. When using EAP to prevent and treat cardiovascular diseases, it involves the metabolic pathway of glutamate, while when using EAP to prevent and treat cerebrovascular diseases, it involves the homeostasis of the blood-brain barrier and the release of neurotransmitters and nutritional factors. I hope these data can provide experimental basis and reference for the clinical promotion and application of EAP in CCVD treatment.

Remote ischemic preconditioning plays a neuroprotective role in cerebral ischemia-reperfusion mice by inhibiting mitophagy

Remote ischemic preconditioning (RIPC) represents a clinically feasible method for safeguarding vital organs against ischemic injury. However, its specific role in cerebral ischemia-reperfusion (I/R) injury remains to be definitively elucidated. In this study, we investigated the neuroprotective effects of RIPC on mice at 7 days post-cerebral I/R and its involvement in mitophagy and mitochondrial dysfunction. Cerebral I/R led to impaired brain function, as well as structural and functional damage to mitochondria. Notably, RIPC treatment ameliorated the neurological dysfunction induced by cerebral I/R. Compared with the I/R group, the expression levels of NeuN, MBP, PDH, and Tom20 were significantly elevated in the RIPC + I/R group. Furthermore, mitochondria in the RIPC + I/R group exhibited more intact structure compared to those in the I/R group. In mice subjected to I/R injury, RIPC treatment markedly increased ATP content, ADP content, TAN level and glucose uptake while upregulating expression levels of Parkin, Pink1 and P62 proteins; it also reduced both the volume of ischemic foci and the number of mitochondrial autophagosomes along with decreasing LC3B II/I ratio. In conclusion, RIPC may exert a neuroprotective role by inhibiting excessive mitophagy during subacute stages following an ischemic stroke.

Embolic Ischemic Cortical Stroke in a Young Flight Instructor with a Small Patent Foramen Ovale

BACKGROUND: Stroke in young patients is frequently associated with a patent foramen ovale (PFO). Controversy exists over whether the PFO is a cause, a risk factor, or an incidental finding. Estimating the individualized risk of stroke recurrence has been difficult to ascertain. This has implications for aeromedical certification for pilots following stroke recovery. CASE REPORT: A 28-yr-old male flight instructor presented with sudden onset unilateral facial paresthesia, hand weakness, and blurred vision, accompanied by gradual onset bilateral headache. While the cranial symptoms resolved, left hand weakness persisted for 3 d. MRI revealed two punctate ischemic foci in the right precentral gyrus and superior parietal lobe. A transesophageal echocardiogram revealed a PFO with a small bidirectional shunt. His cardiologist and neurologist advised the PFO was unlikely to have caused his stroke and estimated an annual recurrence rate of < 1.8%. He was treated medically and declined PFO closure. He was able to return to flying light-sport aircraft. However, an enduring copilot restriction for general aviation activities was placed on his Class 1 and 2 medical certificates. DISCUSSION: This case highlights the difficulty in determining individualized recurrence risks for pilots recovering from a stroke associated with a PFO. While medical treatment does reduce the risk of recurrence, PFO closure provides marginal additional benefit in certain patients with a risk of side effects. Contemporary evidence-based risk scoring systems combined with echocardiography findings may be used together to better risk stratify patients and suitability for medical aviation recertification. Rengel AC, Gericke C. Embolic ischemic cortical stroke in a young flight instructor with a small patent foramen ovale. Aerosp Med Hum Perform. 2024; 95(10):784–787.

Experimental Model of Cerebral Arterial Air Embolism in Conscious Rats.

In this work, an optimal air supply mode was selected to create a model of cerebral arterial air embolism (CAAE) on conscious male Sprague-Dawley rats (n=49). The efficacy of the selected model (administration of 100 μl/kg of air at a rate of 10 μl/min with an infusion pump) was determined by changes in serum biochemical parameters (cholesterol, alkaline phosphatase, inorganic phosphates, AST, and triglycerides), impaired motor functions in the Rotarod test, and visual assessment of the ischemic foci (staining of frontal sections with 1% triphenyltetrazolium chloride solution) at different terms after AAE. The model of AAE created by us confirmed impairment of coordination and motor function in conscious animals and reproduced the lethal consequences of this condition. The obtained results can serve as the basis for drug testing and the development of new approaches to the treatment of ischemic stroke.

Prevalence of Hypertrophic Cardiomyopathy and ALMS1 Variant in Sphynx Cats in New Zealand.

Recently, hypertrophic cardiomyopathy (HCM) in Sphynx cats has been associated with a variant in the gene encoding Alström syndrome protein 1 (ALMS1). The primary aims of this study were to describe the prevalence of HCM in Sphynx cats in New Zealand, and to assess the association between HCM and the ALMS1 variant in this population. In this prospective study, 55 apparently healthy Sphynx cats from registered Sphynx breeders and pet owners in New Zealand were screened by a cardiologist. A total of 42 of these cats had a repeat cardiac examination after median 1.8 years (range: 1.6-2.2). The frequency of the ALMS1 variant was 70.9% (11 homozygous and 28 heterozygous). At the median age of 5.8 years (range: 2.4-13.1), the prevalence of HCM was 40% (20 out of 55 cats). Three cats with HCM died during the study with congestive heart failure. All three cats had focal but extensive myocardial ischemia or infarction at necropsy. The ALMS1 variant was not associated with the HCM diagnosis. In summary, HCM was common in the studied cohort, suggesting Sphynx cats are predisposed to this disease. While the ALMS1 variant was also frequently detected, it was not associated with HCM in this population.

Effectiveness of remote ischaemic conditioning is not affected by hyper-inflammation in a rat model of stroke

The inflammation and coagulopathy during coronavirus disease (COVID-19) impairs the efficiency of the current stroke treatments. Remote ischaemic conditioning (RIC) has shown potential in recent years to protect the brain and other organs against pathological conditions. This study aimed to evaluate the efficiency of RIC in brain infarct size using TTC staining and lung injury reduction by H&E staining during the hyper-inflammatory response in rats. The inflammation and coagulopathy were assessed by sedimentation rate, haematocrit, systemic oxidative stress and clotting time. Moreover, we observed changes in the cytokine profile. The results of the first part of the experiment showed that the inflammation and lung injury are fully developed after 24 h of intratracheal LPS administration. At this time, we induced focal brain ischaemia and examined the effect of RIC pre- and post-treatment. Our results showed that RIPre-C reduced the infarct size by about 23%, while RIPost-C by about 30%. The lung injury was also reduced following both treatments. Moreover, RIC modulated systemic inflammation. The level of chemokines CINC-1, LIX and RANTES decreased after 24 h of post-ischaemic reperfusion in treated animals compared to non-treated. The RIC-mediated decrease of inflammation was reflected in improved sedimentation rate and hematocrit, as well as reduced systemic oxidative stress. The results of this work showed neuroprotective and lung protective effects of RIC with a decrease in inflammation response. On the basis of our results, we assume that immunomodulation through the chemokines CINC-1, LIX, and RANTES play a role in RIC-mediated protection.

S100b protein as a biological marker of nerve tissue damage in laboratory animals in preclinical studies

Background. For preclinical studies of drugs a relevant task is the selection of specific biochemical markers reflecting damage to the central nervous system, both in toxicological and pharmacological experiments. One of such markers may be protein S100b, the level of which will make it possible to assess the damage of the central nervous system of various genesis. Objective. The aim of the study was to assess changes in the level of S100b protein in the blood and in brain homogenates in brain tissue injuries of various genesis. Design and methods. The study was conducted on males of outbred rats and mice. A total of 62 animals were used: 47 rats and 15 mice. To determine the concentration of S100b protein, ELISA kits Rat S100b/S100 beta Elisa kit (Sandwich Elisa) were used) for rats and Mouse S100b/S100 beta Elisa kit (Sandwich Elisa) for mice. Statistical analysis was performed using licensed GraphPad Prism 9 software. Results: Changes of protein S100B was explored on models of alcohol neuropathy, bilateral and focal cerebral ischemia, traumatic brain injury. Forming of all pa[1]thologies led to increasing of protein S100B both in blood plasma and in brain tissues in case of traumatic brain injury. For alcohol neuropathy, focal and cerebral ischemia and traumatic brain injury changings of this marker level reached statistic meaning. Conclusion. Increased concentration of S100b is a sign of neuronal damage as a result of ischemic, traumatic and toxic factors, as well as in hypoclycemic conditions. Thus, protein S100b can be used in preclinical studies as a marker of brain damage, responding to damage of various genesis in studies of pharmacodynamics and pharmacological safety of drugs.

MANAGEMENT OF CEREBROVASCULAR ACCIDENT THROUGH PANCHAKARMA THERAPY: A CASE STUDY

Cerebrovascular accident (CVA), the third most common cause of death in developing countries, is the term used to describe episodes of focal brain dysfunction due to focal ischemia or haemorrhage. Acute stroke is characterized most commonly by hemiplegia with or without signs of focal higher cerebral dysfunction that has posed a great problem as far as its management is concerned. Ayurveda can help in such conditions. CVA is quite clearly defined along with its symptoms, prognosis and management in Ayurveda in the context of Pakshaghata as a Vatavyadhi, affecting Madhyama Rogamarga, in which Sira (vascular structures) and Snayu (tendons and ligaments) are mainly affected. A 40-year-old male patient diagnosed with non-hemorrhagic infarct presented with left-side hemiplegia and diplopia was admitted to IPD. Panchakarma procedures, including Snehana, Swedana, Shirodhara, Nasya and Basti, were adopted along with other internal medicines. Assessments were done before and after treatment using the National Institute of Health Stroke Scale (NIH-SS). At the end of the treatment, there was considerable improvement in the subjective and objective clinical features. The observations reveal that Panchakarma procedures can play a vital role in managing conditions like Cerebrovascular accidents by combating general debility with extraocular muscle weakness. The recovery was promising and worth detailing.

A molecular brain atlas reveals cellular shifts during the repair phase of stroke.

Ischemic stroke triggers a cascade of pathological events that affect multiple cell types and often lead to incomplete functional recovery. Despite advances in single-cell technologies, the molecular and cellular responses that contribute to long-term post-stroke impairment remain poorly understood. To gain better insight into the underlying mechanisms, we generated a single-cell transcriptomic atlas from distinct brain regions using a mouse model of permanent focal ischemia at one month post-injury. Our findings reveal cell- and region-specific changes within the stroke-injured and peri-infarct brain tissue. For instance, GABAergic and glutamatergic neurons exhibited upregulated genes in signaling pathways involved in axon guidance and synaptic plasticity, and downregulated pathways associated with aerobic metabolism. Using cell-cell communication analysis, we identified increased strength in predicted interactions within stroke tissue among both neural and non-neural cells via signaling pathways such as those involving collagen, protein tyrosine phosphatase receptor, neuronal growth regulator, laminin, and several cell adhesion molecules. Furthermore, we found a strong correlation between mouse transcriptome responses after stroke and those observed in human nonfatal brain stroke lesions. Common molecular features were linked to inflammatory responses, extracellular matrix organization, and angiogenesis. Our findings provide a detailed resource for advancing our molecular understanding of stroke pathology and for discovering therapeutic targets in the repair phase of stroke recovery.

Spontaneously Hypertensive Rats Present Exacerbated Focal Stroke Behavioral Outcomes.

This study aimed to analyze the effects of systemic arterial hypertension (SAH) in a model of permanent ischemic stroke (focal ischemia due to thermocoagulation of pial vessels) on sensorimotor function (cylinder test and patch removal test), behavioral tasks (novelty habituation memory open field task) and cerebral infarct size in adult male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 42 days after the occurrence of a stroke. We observed that the stroke caused asymmetry in the front paws and delayed adhesive removal. These effects were spontaneously reduced in WKY rats, but not in SHR. Short- and long-term novelty habituation memories were abolished by stroke in WYK and SHR. On the 3rd day after stroke, the size of the focal cerebral infarct was the same in WKY and SHR. However, on the 7th day, the infarct size decreased in WKY rats, but not SHR. These results suggested that SAH impairment of sensorimotor recovery in rats subjected to cerebral ischemia could be related to augmented focal cerebral infarct size. Moreover, the behavioral tasks used in this study were unaffected by Systemic Arterial Hypertension. Our results highlight the need for animal models of comorbidities in stroke research.

Transesophageal echocardiography guidance for percutaneous closure of PFO and a new method to improve the diagnosis and safety during the procedures.

Percutaneous patent foramen ovale (PFO) closure is becoming more and more common for the treatment or prevention of PFO-associated right-to-left shunt (RLS). This study aims to investigate the value of transesophageal echocardiography (TEE) in percutaneous PFO closure, and to explore a new method that can improve intraoperative diagnosis and surgical safety. Based on our inclusion and exclusion criteria, we enrolled 73 patients between 16 and 70 years old (average age 43.25 ± 14.87 years) who underwent percutaneous PFO closure at the Department of Cardiac Surgery, Zhongshan Hospital (Xiamen), Fudan University, from January 2022 to December 2023. Out of the 73 enrolled patients, there were 28 males (38.36%) and 45 females (61.64%), 29 migraine patients (39.73%), 14 patients (19.19%) with headache and dizziness, 14 patients (19.18%) with a history of cerebral infarction (CI), and 25 patients (34.25%) with CI, lacunar infarction or ischemic focus on magnetic resonance imaging (MRI). All patients received routine transthoracic echocardiography (TTE) and agitated saline contrast echocardiography (ASCE) before operations. Percutaneous closure of PFO was completed under the guidance of TEE. In 12 patients, the method of "injection of heparinized sterile saline through the delivery sheath" was used to observe their RLS, and the anatomical characteristics of the PFO according to the shunt path were monitored and evaluated. This method was also applied to some patients to guide the conveyor to pass through the foramen ovale (FO) channel safely and effectively, thereby improving the success rate of PFO closure. The application of TEE during the procedure of percutaneous PFO closure, including preoperative evaluation, intraoperative guidance, and postoperative reevaluation, can offer further details about the anatomical and shunt characteristics of PFO, improve the diagnosis rate, and confirm the safety of the surgical path. It ensures the safety and reliability of the whole operation, greatly improving the success rate and reducing postoperative complications. TEE guidance of percutaneous PFO closure has the advantages of minimal trauma, no radiation and real-time visualization, while injecting heparinized sterile saline through the delivery sheath is safer and more effective in improving the success rate and reducing postoperative complications.

Neuronal HIPK2-HDAC3 axis regulates mitochondrial fragmentation to participate in stroke injury and post-stroke anxiety like behavior

Post-stroke anxiety (PSA) seriously affects the prognosis of patients, which is an urgent clinical problem to be addressed. However, the pathological mechanism of PSA is largely unclear. Here, we found that neuronal HIPK2 expression was upregulated in the ischemic lesion after stroke. The upregulation of HIPK2 promotes Drp1 oligomerization through the HDAC3-dependent pathway, leading to excessive mitochondrial damage. This subsequently triggers the release of cellular cytokines such as IL-18 from neurons under ischemic stress. Microglia are capable of responding to IL-18, which promotes their activation and enhances their phagocytosis, ultimately resulting in the loss of synapses and neurons, thereby exacerbating the pathological progression of PSA. HIPK2 knockdown or inhibition suppresses excessive pruning of neuronal synapses by activated microglia in the contralateral vCA1 region to compromise inactivated anxiolytic pBLA-vCA1Calb1+ circuit, relieving anxiety-like behavior after stroke. Furthermore, we discovered that early remimazolam administration can remodel HIPK2-HDAC3 axis, ameliorating the progression of PSA. In conclusion, our study revealed that the neuronal HIPK2-HDAC3 axis in the ischemic focus regulates mitochondrial fragmentation to balance inflammation stress reservoir to participate in anxiety susceptibility after stroke.

Neuroprotective Effect of Ganoderic Acid against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion in the Rats via Suppression of Oxidative Stress and Inflammation.

Swiss Wistar rats were used for the current study. The rats were subjected to middle cerebral artery occlusion (MCAO) to simulate transient focal ischemia, followed by reperfusion. Various neurological parameters, including infarct size, neurological deficit score, brain water content, Evans blue leakage, nitric oxide (NO), inducible nitric oxide synthase (iNOS), lactate dehydrogenase (LDH), antioxidant levels, inflammatory cytokines, apoptosis markers, inflammatory parameters, and matrix metalloproteinases (MMP) levels, were estimated. Additionally, mRNA expressions were evaluated in the brain tissue. Dose dependently treatment of GA significantly (P < 0.001) suppressed the infarct size, neurological deflects score, brain water, evans blue leakage, NO, iNOS, LDH, C-X-C chemokine receptor type 4 (CXCR-4), monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein B (S-100β) and K+-Cl- cotransporter 1 (KCC1) positive cells. GA altered the level of oxidative stress parameters like Total antioxidant capacity (T-AOC), 8-hydroxy-2'-deoxyguanosine (8-OhdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), malonaldehyde (MDA); cytokines viz., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-1β, IL-6, IL-9, IL-10; inflammatory parameters such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), Nuclear factor kappa B (NF-κB); apoptosis parameters like B-cell leukemia/lymphoma 2 protein (Bcl-2), Bcl-2-associated protein x (Bax), Caspase-3; matrix metallopeptidase (MMP) parameters like MMP-2, MMP-3, and MMP-9, respectively. GA remarkably suppressed the mRNA expression of TRL-4, Syndecan-1, CSF, Aquaporin-1, OCT3, and RFX1. Ganoderic acid exhibited the protection against the cerebral ischemia reperfusion via multiple mechanism.