Bilateral Carotid Artery Occlusion Research Articles

Moyamoya disease in a 5-year child secondary to MOG antibody-positive cerebral cortical encephalitis.

A 5-year-old girl presented with complaints of fever, left-sided hemiparesis, and left upper motor neuron facial nerve palsy following oral polio booster dose vaccination. She had a past history of fever with altered sensorium with complete resolution at 3years of age. Cerebrospinal fluid evaluation and stool examination were inconclusive. MRI with MRA showed T2 hyperintensities of the right fronto-temporo-parietal cortex with diffusion restriction and occlusion of bilateral internal carotid arteries and collateral formation suggestive of Moyamoya disease with cerebral cortical encephalitis. Evaluation of encephalitis revealed positivity for anti-myelin oligodendrocyte (MOG) antibodies. She showed a good response to intravenous immunoglobulin and pulse steroids with resolution of encephalitis and facial nerve palsy and improvement in the power of the left side of the body. We presume that the Moyamoya disease in this case is possibly secondary to myelin oligodendrocyte antibody-associated disease.

The chronic cerebral hypoperfusion model induces proinflammatory cascades in Alzheimer's disease

Cerebral neuroinflammation has emerged as a significant pathway contributing to the progression of Alzheimer's disease (AD) pathology. Research implicates the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome complex, initiating caspase 1-mediated maturation of interleukin-1 β (IL-1β) and interleukin-18 (IL-18). This study investigates whether chronic cerebral hypoperfusion (CCH), induced via permanent bilateral occlusion of the common carotid arteries (PBOCCA), leads to cognitive dysfunction and NLRP3 inflammasome activation. Twenty male Sprague Dawley (SD) rats underwent PBOCCA to induce CCH. Two weeks post-surgery, locomotor and Morris water maze (MWM) tests were conducted to examine motor functions, spatial learning, and memory, respectively. The gene expression levels of cathepsin B, NLRP3, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 were analysed using real-time PCR, while the expression levels of the inflammatory cytokines were estimated using the ELISA method. Structural damage to the hippocampus was assessed using hematoxylin and eosin (HE) staining. Escape latencies and time spent in specific quadrants in PBOCCA significantly increased compared to sham-operated animals. There was no notable difference in locomotor activity between the PBOCCA and sham-operated groups. The number of pyknotic neurons with cytoplasmic shrinkage increased in the hippocampus. Gene expression of cathepsin B, NLRP3, ASC, and caspase-1 was upregulated in the PBOCCA group. The expression levels of IL-1β, IL-18, interleukin-6 (IL-6), and amyloid-β 1-42 (Aβ 1-42) were elevated in the PBOCCA group relative to sham. The findings confirm NLRP3 inflammasome induction, cognitive dysfunction, and inflammatory cytokines associated with AD and cerebral ischemia. The PBOCCA model provides a valuable tool for studying neurodegenerative including AD.

Edaravone dexborneol attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory responses and modulating the NMDA receptor signaling pathway

Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new brain-protective medication developed in China, Edaravone dexboeol (EDB), has shown promise due to its antioxidant and anti-inflammatory properties, albeit with a need for additional research to elucidate its role and mechanisms in VD contexts. In a research setup, a VD model was established utilizing Sprague-Dawley (SD) rats, subjected to permanent bilateral typical carotid artery occlusion (2VO). Behavioral assessment of the rats was conducted using the Bederson test and pole climbing test, while cognitive abilities, particularly learning and memory, were evaluated via the novel object recognition test and the Morris water maze test. Ensuing, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), IL-1β, IL-6, IL-4, and tumor necrosis factor-α (TNF-α) were determined through Enzyme-Linked Immunosorbent Assay (ELISA). Synaptic plasticity-related proteins, synaptophysin (SYP), post-synaptic density protein 95 (PSD-95), and N-methyl-D-aspartate (NMDA) receptor proteins (NR1, NR2A, NR2B) were investigated via Western blotting technique. The findings imply that EDB has the potential to ameliorate cognitive deficiencies, attributed to VD, by mitigating oxidative stress, dampening inflammatory responses, and modulating the NMDA receptor signaling pathway, furnishing new perspectives into EDB’s mechanism and proposing potential avenues for therapeutic strategies in managing VD.

Floralozone regulates MiR-7a-5p expression through AMPKα2 activation to improve cognitive dysfunction in vascular dementia

BackgroundThe pathogenesis of vascular dementia (VD) is complex, and currently, no effective treatments have been recommended. Floralozone is a colorless liquid first discovered in Lagotis Gaertn. Recently, its medicinal value has been increasingly recognized. Our previous study has demonstrated that Floralozone can improve cognitive dysfunction in rats with VD by regulating the transient receptor potential melastatin 2 (TRPM2) and N-methyl-D-aspartate receptor (NMDAR) signaling pathways. However, the mechanism by which Floralozone regulates TRPM2 and NMDAR to improve VD remains unclear. AMP-activated protein kinase (AMPK) is an energy regulator in vivo; however, its role of AMPK activation in stroke remains controversial. MiR-7a-5p has been identified to be closely related to neuronal function. PurposeTo explore whether Floralozone can regulate the miR-7a-5p level in vivo through AMPKα2 activation, affect the TRPM2 and NR2B expression levels, and improve VD symptoms. MethodsThe VD model was established by a modified bilateral occlusion of the common carotid arteries (2-VO) of Sprague-Dawley (SD) rats and AMPKα2 KO transgenic (AMPKα2−/−) mice. Primary hippocampal neurons were modeled using oxygen and glucose deprivation (OGD). Morris water maze (MWM) test, hematoxylin-eosin staining (HE staining), and TUNEL staining were used to investigate the effects of Floralozone on behavior and hippocampal morphology in rats. Minichromosome maintenance complex component 2(MCM2) positive cells were used to investigate the effect of Floralozone on neurogenesis. Immunofluorescence staining, qRT-PCR, and western blot analysis were used to investigate the effect of Floralozone on the expression levels of AMPKα2, miR-7a-5p, TRPM2, and NR2B. ResultsThe SD rat experiment revealed that Floralozone improved spatial learning and memory, improved the morphology and structure of hippocampal neurons, reduced apoptosis of hippocampal neurons and promoted neurogenesis in VD rats. Floralozone could increase the miR-7a-5p expression level, activate AMPKα2 and NR2B expressions, and inhibit TRPM2 expression in hippocampal neurons of VD rats. The AMPKα2 KO transgenic (AMPKα2−/−) mice experiment demonstrated that Floralozone could regulate miR-7a-5p, TRPM2, and NR2B expression levels through AMPKα2 activation. The cell experiment revealed that the TRPM2 and NR2B expression levels were regulated by miR-7a-5p, whereas the AMPKα2 expression level was not. ConclusionFloralozone could regulate miR-7a-5p expression level by activating the protein expression of AMPKα2, control the protein expression of TRPM2 and NR2B, improve the morphology and structure of hippocampus neurons, reduce the apoptosis of hippocampus neurons, promote neurogenesis and improve the cognitive dysfunction.

Acute concurrent bilateral internal carotid artery occlusion: a teaching clinical image

Acute bilateral internal carotid artery (ICA) occlusion is a rare stroke syndrome presenting with acute coma, and patients usually have preserved brainstem function on initial examination. In this clinical image, we report a case of acute concurrent bilateral ICA occlusion. Acute bilateral ICA occlusion is an unusual entity with a poor outcome. It can mimic metabolic encephalopathies and posterior circulation infarcts and can be differentiated by careful evaluation of brainstem functions.

Probucol protects against brain damage caused by intra-neural pyroptosis in rats with vascular dementia through inhibition of the Syk/Ros pathway.

Neuronal injury in chronic cerebral hypoperfusion (CCH) is the main pathogenic factor of vascular dementia (VD). Clinically, there isn't a drug specifically for VD; instead, the majority of medications used to treat Alzheimer's disease (AD) are also used to treat VD. Based on the proven anti-inflammatory and antioxidant effects of Probucol, we hypothesized that it may have therapeutic effects on VD, but more research is required to determine its exact mechanism of action. In vivo experiment: We used SD rats and most commonly used bilateral carotid artery occlusion (2-VO) in VD for modeling. After successful modeling, SD rats were given Probucol 3.5 mg/kg/day for 8 weeks to evaluate the therapeutic effect. In vitro experiment: BV-2 microglia of rats were cultured and divided into Control group and Probucol group. Each group was treated with hypoxia-hypoglycemia, hypoxia-hypoglycemia hydrogen peroxide and hypoxia-hypoglycemia hydrogen peroxide Syk inhibitor respectively. The results of immunofluorescence and Western blot showed that Probucol could significantly improve the cognitive impairment induced by CCH, and the neuronal damage was also attenuated. On the one hand, the underlying mechanism of Probucol was to reduce oxidative stress and cell apoptosis of hippocampal neurons by inhibiting the expression of phosphorylated spleen tyrosine kinase (P-Syk); On the other hand, it exerted a protective effect by reducing NLRP3-dependent cell pyroptosis and inhibiting neuroinflammation induced by microglia activation. Probucol could reduce oxidative stress and cell apoptosis by inhibiting the Syk/ROS signaling pathway, thereby improving CCH-induced cognitive impairment in vitro and in vivo.

Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion

Neurovascular unit mural cells called ‘pericytes’ maintain the blood-brain barrier and local cerebral blood flow. Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 post-mortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25–40% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1 ± 0.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (P = 0.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (P < 0.001). Pericyte densities were correlated with CA1 volumes (r = 0.54, P = 0.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection.

7, 8-dihydroxyflavone Ameliorates Cholinergic Dysfunction, Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Vascular Dementia.

Vascular dementia (VD) is a degenerative cerebrovascular disorder associated with progressive cognitive decline. Previous reports have shown that 7,8-dihydroxyflavone (7,8-DHF), a well-known TrkB agonist, effectively ameliorates cognitive deficits in several disease models. Therefore, this study investigated the protective effects of 7,8-DHF against 2-VO-induced VD.VD was established in rats using the permanent bilateral carotid arteries occlusion (two-vessel occlusion, 2-VO) model. 7,8-DHF (5, 10, and 20mg/kg) and Donepezil (10mg/kg) were administered for 4 weeks. Memory function was assessed by the novel objective recognition task (NOR) and Morris water maze (MWM) tests. Inflammatory (TNF-α, IL-1β, and NF-kβ), oxidative stress, and apoptotic (BAX, BCL-2, caspase-3) markers, along with the activity of choline acetylcholinesterase (AChE) was assessed. p-AKT, p-CREB, BDNF, and neurotransmitter (NT) (GLU, GABA, and ACh) levels were also analyzed in the hippocampus of 2-VO rats.Our results show that 7,8-DHF effectively improved memory performance and cholinergic dysfunction in 2-VO model rats. Furthermore, 7,8-DHF treatment also increased p-AKT, p-CREB, and BDNF levels, suppressed oxidative, inflammatory, and apoptotic markers, and restored altered NT levels in the hippocampus.These findings imply that 7, 8-DHF may act via multiple mechanisms and as such serve as a promising neuroprotective agent in the context of VD.

Spontaneous development and involution of a de novo pseudoaneurysm at the superficial temporal artery-middle cerebral artery bypass anastomotic site in a patient with moyamoya disease: illustrative case.

De novo pseudoaneurysm formation is a rare complication of extracranial-intracranial bypass surgery. The authors report the case of a 28-year-old male who presented with new-onset right temporal and occipital ischemia who was found to have bilateral proximal internal carotid artery occlusion with collateral vasculature formation consistent with moyamoya disease. The patient underwent bilateral superficial temporal artery-middle cerebral artery bypasses. A de novo pseudoaneurysm was found at the left-sided bypass distal anastomotic site recipient vessel 1 month after the surgery. The pseudoaneurysm demonstrated a progressive reduction in size and eventual complete involution at 6 months after surgery. Limited literature reports extracranial-intracranial bypass-associated aneurysms treated primarily with either clipping or resection and reanastomosis. The authors demonstrate, for the first time, a progressively benign natural history course of an extracranial-intracranial bypass distal anastomotic site pseudoaneurysm.

Impact of Codonopsis decoction on cerebral blood flow and cognitive function in rats with chronic cerebral ischemia

Ethnopharmacological relevanceSome species of Codonopsis (local name in Shanxi: Ludang) have long demonstrated high medicinal and economic value. Radix Codonopsis, the dried root of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. modesta (Nannf.) L.D.Shen (C. pilosula var. modesta), or Codonopsis pilosula subsp. tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), was recorded as a traditional Chinese medicine back in the Qing Dynasty in Ben Cao Cong Xin. Radix Codonopsis, a valuable medicinal herb certified by the Chinese National Geographic Indication, is known for invigorating the spleen, nourishing the lungs, promoting blood circulation, and generating fluid properties. Given that chronic cerebral ischemia (CCI) is often associated with the symptoms of qi and blood deficiencies and fluid depletion, we explored the potential of Codonopsis decoction in the treatment of CCI. Study aimsWe investigated the effects of Codonopsis decoction on cerebral blood flow (CBF) and cognitive function in rats with bilateral carotid artery occlusion after surgery; explored whether Codonopsis decoction alleviates pathological injuries in brain tissue of rats after 2-VO surgery; and assessed the impact of Codonopsis decoction on the expression of chemokines, hypoxia-inducible factors, and inflammatory mediators in rats after 2-VO surgery. Materials and methodsWe used a 2-VO rat model to simulate CCI. We used a laser speckle imaging (LSI) system to observe changes in CBF before and after surgery. The goal was to examine variations in CBF at different time points after 2-VO surgery. For 4 weeks, the rats were orally administered Codonopsis decoction at doses of 2.7, 5.4, and 10.8 g/kg/day, or Ginaton at a dose of 43.2 mg/kg/day. To assess the effect of Codonopsis on cerebral hypoperfusion symptoms in rats, we conducted the Morris water maze (MWM), Barnes maze (BM), and forelimb grip strength tests. Additionally, pathological experiments including hematoxylin and eosin, Nissl, and Luxol fast blue staining were conducted. Furthermore, we used western blotting to detect changes in the levels of proteins such as the chemotactic factor CKLF1 and hypoxia-inducible actor 1-alpha (HIF-1α). ResultsOne week after 2-VO surgery, cerebral arterial blood supply in the rats rapidly reduced to approximately 43.39% ± 3.53% of the preoperative level. Cerebral cortex perfusion reached its nadir within 24 h of surgery, gradually recovering and stabilizing by the fourth week after surgery. An integration of the results from the BM, MWM, and grip strength tests, which assessed cognitive function and forelimb strength in rats after 2-VO surgery, unequivocally revealed that Codonopsis treatment significantly reduced the latency period and increased the number of platform crossings in the MWM test. Ginaton exhibited a comparable effect. Moreover, both Codonopsis and Ginaton decreased the number of errors and the time required to locate the target hole in the BM test. Histopathological staining revealed that Codonopsis and Ginaton could ameliorate pathological damage in rats after CCI and reduce the release of factors such as CKLF1 and HIF-1α. ConclusionCodonopsis decoction exerted its protective effects on CCI rats possibly by modulating the levels of chemokines, hypoxia-inducible factors, and neuroinflammatory mediators.

Multipotent mesenchymal stromal cells of various origins reduce reactive gliosis in the hippocampal CA1 area during acute ischemia-reperfusion of the rat brain

Neuroprotective therapy in acute cerebrovascular disorders is directly aimed at preserving neurons in the penumbra zone, but it also emphasizes the importance of gliogenesis in the affected area. Glial cells exhibit rapid reactivity and are highly sensitive to cerebral ischemic damage. Recent experimental studies have demonstrated the successful application of multipotent mesenchymal stromal cells (MMSCs) in stroke to modulate microglial activation. The aim of the study was to investigate the impact of MMSCs of different origins, MMSC lysate, and citicoline on glial components in a model of cerebral ischemia-reperfusion in rats. Materials and methods. The experiments were conducted on 190 male Wistar rats aged 4 months, weighing 160-190 g. After modeling cerebral ischemia-reperfusion through bilateral 20-minute occlusion of the internal carotid arteries, rats were intravenously administered MMSCs derived from human Wharton’s jelly, human adipose tissue, and rat Wharton’s jelly at a dose of 106 cells per animal. Other groups received fetal rat fibroblasts (106 cells/animal in 0.2 ml of physiological solution) and lysate from human Wharton’s jelly at a dose of 0.2 ml per animal. Control animals received 0.2 ml of physiological solution intravenously. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th days, the area and fluorescence intensity of cells expressing markers of astrocytes (GFAP), microglia (Iba1), and oligodendrocytes (Rip) were quantitatively assessed in CA1 hippocampal region slices using immunohistochemical examination and confocal microscopy. Results. On the 7th and 14th days after cerebral ischemia-reperfusion in rats, the intensity of fluorescence of GFAP-positive astrocytes and Iba1-positive microglial cells increased, indicating pronounced reactive astrogliosis and microglial activation in the CA1 region of the hippocampus. Meanwhile, ischemia-reperfusion had a significant impact on the content of Rip-positive oligodendrocytes in brain slices. The application of all treatments (transplantation of MMSCs of different origins, their lysate, or the reference drug citicoline) had a cytoprotective effect, reducing reactive astrogliosis and microgliosis both on the 7th and 14th days after injury. The best result was demonstrated with the treatment using MSCs from human Wharton’s jelly.s. Conclusion. Cerebral ischemia-reperfusion induces reactive gliosis through the activation of GFAP- and Iba1-positive glial cells in all layers of the hippocampus. The application of MSCs from human Wharton’s jelly and fetal rat fibroblasts significantly reduces its intensity on both the 7th and 14th days after injury modeling.

Regulation of ABCB1 Protein Function in the Cerebral Cortex with the Underlying Global Cerebral Ischemia

INTRODUCTION: ABCB1 is a membrane transporter protein responsible for efflux of a wide range of drugs from cells. The study of the mechanisms of regulation of the functioning of ABCB1 protein in the brain in its ischemia will permit to propose new approaches to pharmacotherapy of cerebral ischemic pathology.&#x0D; AIM: To study the regulation of ABCB1 protein function in the cerebral cortex of rats with global cerebral ischemia.&#x0D; MATERIALS AND METHODS: The experiment was performed on 30 male rats with global cerebral ischemia modeled by bilateral occlusion of the common carotid arteries. The amount of ABCB1 protein and Nrf2 and HIF-1α transcription factors in the cerebral cortex was determined by enzyme immunoassay. The free radical status of the cerebral cortex was assessed by the concentration of malondialdehyde, SH groups, and by glutathione peroxidase (G-per) activity.&#x0D; RESULTS: Bilateral occlusion of the common carotid arteries caused an increase in the level of ABCB1 protein in the cerebral cortex of rats by the 4th hour of ischemia; in 24 hours it remained elevated, and in 72 hours decreased to values that did not differ from those of falsely operated rats. The content of malondialdehyde in the cerebral cortex increased in 2 and 4 hours after occlusion and then gradually decreased to the initial values. In 30 minutes and 4 hours after ischemia modeling, G-per activity decreased compared to the control values. The content of Nrf2 in the cerebral cortex increased in 2 and 4 hours after occlusion, then slightly decreased on the next day, and reached the initial values on the 3rd day of the experiment. The amount of HIF-1α increased only in 24 and 72 hours after the surgery.&#x0D; CONCLUSION: The amount of ABCB1 protein in the cerebral cortex of rats with global cerebral ischemia depends on the severity of oxidative stress, with Nrf2 and HIF-1α transcription factors playing a role in its regulation. Reduction of the amount of the transporter in the blood-brain barrier through the influence on the lipid peroxidation processes or synthesis of the studied transcription factors expands the possibilities of using ABCB1 protein substrates for improving the effectiveness of pharmacotherapy of diseases of the central nervous system.

Recurrent Stroke in Young Adult as a Manifestation of Moyamoya Disease: Case Report

Background: Moyamoya disease is a chronic cerebrovascular disorder characterized by progressive narrowing of the intracranial portions of the distal internal carotid artery, the initial proximal components of the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. Moyamoya disease can manifest as a stroke in young adult. Methods: This report presents a young female patient with Moyamoya disease in Siloam Hospital Denpasar, Bali, Indonesia, diagnosed using MRI and Digital Subtraction Angiography. Case Report: A 29-year-old woman with recurrent stroke, presented with right-side hemiparesis, urinary incontinence, disinhibition syndrome, hypertension, and a history of left hemiparesis from a previous stroke. The MRI brain showed hyperintensity throughout the sulci (ivy sign) in the bilateral frontoparietal with acute infarct in the left frontomedial region, chronic infarct in right frontomedial, occlusion of bilateral carotid arteries (supraclinoid segment), bilateral MCA and ACA. The cerebral DSA study showed stenosis in the right ICA, stenosis in the M1-M2 junction with poor collateral to ACA territory with a puff of smoke appearance, occlusion in the left ICA (supraclinoid segment), and severe stenosis in M1. The patient had undergone direct bypass in the right MCA and right superficial temporal artery. Unfortunately, the bypass did not succeed because of infection of the bypass site and the patient got oral medication with a single antiplatelet (asetosal) and angiotensin receptor blocker (valsartan). Discussion: Moyamoya disease is a rare chronic cerebrovascular disorder that can manifest as an ischaemic stroke in young adult. This patient had a recurrent ischaemic stroke due to Moyamoya disease. According to a global multicenter stroke database, 90% of Moyamoya disease patients initially presented with an ischemic stroke, 7.5% with a transient ischemic attack, and 2.5% with a hemorrhagic stroke. DSA showed that the intracranial collateral system failed to fulfill the demand for brain circulation when the stroke occurred. The patient had failure to grow collateral after direct bypass surgery from the right superficial temporal artery to MCA and single oral antiplatelet as a secondary prevention for ischaemic stroke. Conclusion: Moyamoya disease is a rare disease that needs further studies for its treatment to halt the progression and prevent secondary complications. Young patients with ischaemic stroke needed to be asses with brain MRI, MRA, and DSA to evaluate the etiology of ischaemic stroke. Keywords: Moyamoya disease, Digital Substraction Angiography,ischaemic stroke

Changes in the cerebral cortex and thyroid in the simulation of cerebral hypoperfusion and its combination with physical exercise

Cerebral hypoperfusion, as the main mechanism of age-associated diseases, is widespread, which leads to decreased work capacity in the most qualified segment of employees. The study aimed to analyze compensatory and adaptive reactions of the cerebral cortex, thyroid gland, and blood in cerebral hypoperfusion and its combination with short-term physical activity. Chronic cerebral hypoperfusion was modeled by permanent bilateral occlusion of the common carotid arteries. The study included 280 rats, of which 112 were subjected to daily short-term swimming as a model of rehabilitation measures. On days 1, 6, 8, 14, 21, 28, 35, 60, and 90 after surgery, the animals were subjected to the Morris water maze and open field tests. Histological sections of the brain and thyroid gland were examined. The concentrations of the active products of thiobarbituric acid, nitrites, and L-arginine in blood plasma were measured. The results showed that changes in the cerebral cortex and thyroid gland in the cerebral hypoperfusion model were characterized by a general stage: days 18, hypothyroid condition and death of cortical cells, cerebral hemispheres, predominantly neurons; weeks 23, stabilization, transition to the euthyroid condition, accompanied with thyrocyte desquamation, folliculogenesis, perifollicular hemocapillaries fullness, decreased functional activity of neurons, and astrocyte activation; weeks 45, incomplete adaptation, which is characterized by neurons approaching the vessels of the hemocirculatory channel and satellites sinking into the cytoplasm of neurons. Mosaicism of thyroid blood filling was also observed. After 3 months, degenerative changes in the cells of the cerebral cortex of the cerebral hemispheres appear, including a decrease in the numerical density of neurons and immunoreactive cells of glial fibrillar acid protein and a hyperthyroid state with signs of decompensation: plasmorrhagia and desquamation of the thyroid epithelium. Daily 15-min exercise with cerebral hypoperfusion demonstrated a neuroprotective effect, slowed down the progression of hypoxic and neurodegenerative changes, and reduced the concentration of nitrites and malondialdehyde in the blood and the levels of neuronal nitric oxide synthase in immunoreactive neurons.

Neuroprotective effects of ivermectin against transient cerebral ischemia-reperfusion in rats.

Stroke is a leading cause of disability and death worldwide. Ivermectin is a broad-spectrum anti-parasitic agent with potential anti-bacterial, anti-viral, and anti-cancer effects. However, the effects of ivermectin on the brain are poorly described. This study examined the effects of ivermectin on cerebral ischemia-reperfusion (IR) in rats. A rat model of transient global IR was induced by bilateral carotid artery occlusion for 20min. Rats received ivermectin (2mg/kg/day, ip) one hour after inducing cerebral IR for three consecutive days at 24-h intervals. Next, we examined the effects of ivermectin on brain infarction, histopathology, malondialdehyde levels, myeloperoxidase activity, spatial learning and memory, and phospho-AMPK protein levels. The results showed that ivermectin reduced brain infarct size (P < 0.001) and histopathological changes such as cerebral leukocyte accumulation and edema (P < 0.05) compared to untreated rats with IR. Treatment with ivermectin also decreased myeloperoxidase activity (P < 0.01) and malondialdehyde levels (P < 0.05) while increasing AMPK activity (P < 0.001), memory, and learning compared to the untreated IR group. Overall, we show for the first time that ivermectin conferred neuroprotective effects in a rat model of cerebral IR. Our results indicate that three days of treatment with ivermectin reduced brain infarct size, lipid peroxidation, and myeloperoxidase activity and improved memory and learning in rats with cerebral IR. These effects likely occurred via AMPK-dependent mechanisms.

Bilateral sudden sensorineural hearing loss due to subcortical cerebral hemorrhage in a patient with Moyamoya disease: case report

BackgroundMoyamoya disease (MMD) is a chronic cerebrovascular occlusive disease that can results in a variety of neurological deficits. We describe a very rare presentation of MMD in the form of bilateral sudden sensorineural hearing loss after a second attack of subcortical cerebral haemorrhage.Case presentationA 44-year-old female presented with bilateral sudden sensorineural hearing loss (SSNHL) secondary to an acute intracerebral haemorrhage in the left temporoparietal region. She had a previous haemorrhagic event in the right temporoparietal region two years ago. The two haemorrhagic events have apparently led to interruption of the auditory pathways bilaterally, resulting in sudden complete deafness. Digital subtraction angiography was done, and it showed bilateral occlusion of the internal carotid arteries, with the abnormal anastomotic vascular network at the base of the brain characteristic for MMD.ConclusionsSubcortical hemorrhage due to MMD is a potential cause of bilateral SSNHL that can be diagnosed with early proper imaging. Bilateral damage of the auditory pathways is the likely cause of cortical deafness in this clinical scenario.

The Role of NMDA Receptor Partial Antagonist, Carbamathione, as a Therapeutic Agent for Transient Global Ischemia.

Carbamathione (Carb), an NMDA glutamate receptor partial antagonist, has potent neuroprotective functions against hypoxia- or ischemia-induced neuronal injury in cell- or animal-based stroke models. We used PC-12 cell cultures as a cell-based model and bilateral carotid artery occlusion (BCAO) for stroke. Whole-cell patch clamp recording in the mouse retinal ganglion cells was performed. Key proteins involved in apoptosis, endoplasmic reticulum (ER) stress, and heat shock proteins were analyzed using immunoblotting. Carb is effective in protecting PC12 cells against glutamate- or hypoxia-induced cell injury. Electrophysiological results show that Carb attenuates NMDA-mediated glutamate currents in the retinal ganglion cells, which results in activation of the AKT signaling pathway and increased expression of pro-cell survival biomarkers, e.g., Hsp 27, P-AKT, and Bcl2 and decreased expression of pro-cell death markers, e.g., Beclin 1, Bax, and Cleaved caspase 3, and ER stress markers, e.g., CHOP, IRE1, XBP1, ATF 4, and eIF2α. Using the BCAO animal stroke model, we found that Carb reduced the brain infarct volume and decreased levels of ER stress markers, GRP 78, CHOP, and at the behavioral level, e.g., a decrease in asymmetric turns and an increase in locomotor activity. These findings for Carb provide promising and rational strategies for stroke therapy.

Comparison of Bilateral Carotid Artery Occlusion and Stenosis in Inducing Behaviour and Structural Changes in Rodents

This study aimed to compare the effects of bilateral common carotid artery occlusion (BCCAO) and bilateral carotid artery stenosis (BCAS) on brain function and structure in rodents. Adult male Sprague-Dawley rats and C57BL/6 mice were randomly assigned to either the BCCAO or sham group and the BCAS or sham group, respectively. Neurobehavioral assessments were conducted using various tests, and histological examination was performed to evaluate brain structure. Both surgeries induced white matter damage, with BCCAO mainly affecting the hippocampus and BCAS affecting the blood flow. BCCAO rats exhibited anxiety-like behaviors and cognitive impairment at week 8, while BCAS mice showed significant cognitive deficits at week 4. Both surgeries caused cellular responses to white matter damage, with increased astrocytes and microglial/macrophagemarkers observed in the corpus callosum region. Physical growth and development were not significantly impacted, and there was no difference in bilateral cerebral blood flow between the surgery and sham groups. In conclusion, both models induced significant cognitive impairment and white matter damage. BCCAO induced anxiety-like behaviors at a later stage compared to BCAS, which could help researchers study the underlying mechanisms of chronic cerebral ischemia and drug evaluation.

Edaravone Dexborneol Alleviates Neuroinflammation by Reducing Neuroglial Cell Proliferation and Suppresses Neuronal Apoptosis/Autophagy in Vascular Dementia Rats.

More and more evidence shows that the pathological mechanism of vascular dementia (VD) is closely related to oxidative stress injury, cell apoptosis, autophagy, inflammatory response, excitatory amino acid toxicity, synaptic plasticity change, calcium overload, and other processes. Edaravone dexborneol (EDB) is a new type of neuroprotective agent that can improve the neurological damage caused by an ischemic stroke. Previous studies showed that EDB has effects on synergistic antioxidants and induces anti-apoptotic responses. However, it remains unclear whether EDB can affect apoptosis and autophagy by activating the PI3K/Akt/mTOR signaling pathway and its impact on the neuroglial cells. In this study, we established the VD model of rats by bilateral carotid artery occlusion to explore the neuroprotective effect of EDB and its mechanism. Morris Water Maze test was applied to assess the cognitive function of rats. H&E and TUNEL staining were applied to observe the cellular structure of the hippocampus. Immunofluorescence labeling was used to observe the proliferation of astrocytes and microglia. ELISA was applied to examine the levels of TNF-α, IL-1β and IL-6, and RT-PCR was applied to examine their mRNA expression levels. Western blotting was applied to examine apoptosis-related proteins (Bax, Bcl-2, Caspase-3), autophagy-related proteins (Beclin-1, P62, LC3B), PI3K/Akt/mTOR signaling pathway proteins and their phosphorylation levels. The results indicated that EDB ameliorates learning and memory in rats subjected to the VD model, alleviates neuroinflammatory response by reducing the proliferation of the neuroglial cell and inhibits apoptosis and autophagy, which may be mediated by the PI3K/Akt/mTOR signaling pathway.

Management of Cerebral 4-Vessel Disease With Anterior Circulation Symptoms by Stenting Both Vertebral Arteries at the Same Session.

Stroke is among the leading causes of mortality and morbidity worldwide. The coexistence of bilateral carotid and vertebral artery (VA) occlusion and/or stenosis is in the very rare entity group in the literature. Here, we present a case with bilateral carotid artery occlusion and bilateral VA stenosis, who presented with an atypical clinical presentation and underwent bilateral vertebral percutaneous transluminal angioplasty (PTA) and stenting in the same session. A 67 year old male patient was brought to the emergency department with complaints of inability to speak and weakness in both legs for 1 day. There were bilateral infarct areas in the anterior cerebral artery region and an additional infarct area in the left middle cerebral artery region. First, the right VA stenosis level was crossed using a 0.14 guidewire. After PTA, balloon-expandable stenting was performed with a 3.0×12 mm NC (non-compliant) balloon, and nearly complete recanalization was observed. Therefore, it was decided to perform an intervention on the left VA in the same session. As in this example case, in cases where cerebral perfusion is severely impaired, medical treatment after recanalization may be one of the best treatment options. The carotid arteries are the main arteries supplying the anterior circulation, and the vertebral arteries supply blood to the posterior circulation. However, in cases where both carotid arteries are occluded/dysfunctional, all cerebral perfusion remains over the vertebrobasilar system. However, in cases such as this, where both carotid arteries are occluded/dysfunctional, all cerebral perfusion remains over the vertebrobasilar system and may be responsible for anterior circulation strokes. The situation becomes more severe if both vertebral artery critical stenosis is added. Synchronous carotid and vertebral artery revascularization is not recommended in the guidelines for patients with combined carotid and vertebral artery disease. In patients with four-vessel occlusion/stenosis, as in this particular case, the intervention method and priorities are unclear. We achieved a favorable clinical outcome with simultaneous bilateral vertebral artery angioplasty and stenting, a hazardous method that can be a guide as an approach option in similar cases.