Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE44289 | GEO | 2013/02/14
SECONDARY ACCESSION(S): PRJNA189325
REPOSITORIES: GEO
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Project description:BackgroundChronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO) in rats has been commonly used for the study of Alzheimer's disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified.MethodsTemporal changes (sham, 21, 35, 45, 55 and 70 days) in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO) and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO.ResultsTwo major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01). Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01). In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis.ConclusionsThe biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.
| S-EPMC3728362 | biostudies-literature
Project description:We measured temporal changes of gene expression in hippocampus of rat after BCCAo using time-course microarray analysis Total RNA from the hippocampus from each time point of 21, 35, 45, 55 and 70 days after the BCCAo were subject to microarray.
2013-02-14 | E-GEOD-44289 | biostudies-arrayexpress
Project description:Retinal hypoperfusion injury is the pathophysiologic basis of ocular ischemic syndrome (OIS) which often leads to severe visual loss. In this study, we aimed to establish a rat model of retinal chronic hypoperfusion by bilateral common carotid artery occlusion (BCCAO) and observe changes in the retinal function and morphology. We found that model rats showed retinal arteriosclerosis, slight dilated retinal vein, small hemangiomas, hemorrhages, vascular segmental filling, and nonperfused areas after 2 weeks of BCCAO. In the model rats, the retinal circulation time was significantly prolonged by fluorescein fundus angiography (FFA), the latency of a and b waves was delayed and the amplitude was decreased significantly at each time point by electroretinogram (ERG), and the perfusion of the eyes continued to reduced. Morphologic and ultrastructural changes covered that the retinal ganglion cells (RGCs) presented obvious apoptosis and the thickness in the retinal layers were significantly thinner. Collectively, these findings suggested that BCCAO induced retinal hypoperfusion injury in the model rats, thus providing an ideal animal model for the study of OIS.
| S-EPMC6331588 | biostudies-literature
Project description:OBJECTIVE:We aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury. METHODS:Thirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400. RESULTS:Brain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group. CONCLUSION:We demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.
| S-EPMC7299602 | biostudies-literature
Project description:ObjectiveWe have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV).MethodsStructural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients.ResultsOf the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively).ConclusionsInterhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.
| S-EPMC8209736 | biostudies-literature
Project description:Animal models of disease are an indispensable element in our quest to understand pathophysiology and develop novel therapies. Ex vivo studies have severe limitations, in particular their inability to study individual disease progression over time. In this respect, non-invasive in vivo technologies offer multiple advantages. We here used bilateral common carotid artery occlusion (BCCAO) in mice, an established model for ischemic retinopathy, and performed a multimodal in vivo and ex vivo follow-up. We used scanning laser ophthalmoscopy (SLO), ocular coherence tomography (OCT) and electroretinography (ERG) over 6 weeks followed by ex vivo analyses. BCCAO leads to vascular remodeling with thickening of veins starting at 4 weeks, loss of photoreceptor synapses with concomitant reduced b-waves in the ERG and thinning of the retina. Mononuclear phagocytes showed fluctuation of activity over time. There was large inter-individual variation in the severity of neuronal degeneration and cellular inflammatory responses. Ex vivo analysis confirmed these variable features of vascular remodeling, neurodegeneration and inflammation. In summary, we conclude that multimodal follow-up and subgroup analysis of retinal changes in BCCAO further calls into question the use of ex vivo studies with distinct single end-points. We propose that our approach can foster the understanding of retinal disease as well as the clinical translation of emerging therapeutic strategies.
| S-EPMC5856268 | biostudies-literature
Project description:Carotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain causing cognitive impairments even if classified asymptomatic without a transient ischemic attack or stroke. Paracrine Interleukin 6 (IL 6) improves functional outcome after stroke. However, in carotid artery disease it might have adverse long-term effects. With this exploratory study, we investigated the effect of paracrine IL 6 on cerebral remodeling in early stages after asymptomatic carotid artery occlusion. Therewith we aimed to distinguish IL 6 dependent targets with beneficial effects for long-term outcome from factors causing the detrimental long-term effects of IL 6. To mimic a human asymptomatic carotid artery disease, we used a mouse model of unilateral common carotid artery (CCA) occlusion. We developed a mouse model for inducible paracrine cerebral IL 6 expression (Cx30-Cre-ERT2;FLEX IL6) and induced IL 6 two days after CCA occlusion. We studied the effects of paracrine IL 6 after CCA occlusion on neuronal connectivity using diffusion tensor imaging and on local proteome regulations of the hypo-perfused striatum and contralateral motor cortex using mass spectrometry of laser capture micro-dissected tissues. Paracrine IL-6 induced cerebral remodeling leading to increased inter-hemispheric connectivity and changes in motor system connectivity. We identified changes in local protein abundance which might have adverse effects on functional outcome such as upregulation of Synuclein gamma (Sncg) or downregulation of Proline Dehydrogenase 1 (Prodh). However, we also identified changes in local protein abundance having potentially beneficial effects such as upregulation of Caprin1 or downregulation of GABA transporter 1 (Gat1).
2022-01-27 | PXD029737 | Pride
Project description:BackgroundBerberine (BBR) is a plant alkaloid that possesses anti-inflammatory and anti-oxidant effects with low oral bioavailability. In this study, micelle formulation of BBR was investigated to improve therapeutic efficacy and examined its effect on the secretion of inflammatory cytokines in cerebral ischemia in the animal model.Material and methodsNano formulation was prepared by thin-film hydration method, and characterized by particle size, zeta potential, morphology, encapsulation efficacy, and drug release in Simulated Gastric Fluid (SGF) and Simulated Intestine Fluid (SIF). Then, Wistar rats were pretreated with the drug (100 mg/kg) and nano-drug (25, 50, 75, 100 mg/kg) for 14 days. Then, on the fourteenth day, stroke induction was accomplished by Bilateral Common Carotid Artery Occlusion (BCCAO); after that, Tumor Necrosis Factor - Alpha (TNF-α), Interleukin - 1 Beta (IL-1ß), and Malondialdehyde (MDA) levels were measured in the supernatant of the whole brain, then the anti-inflammatory effect of BBR formulations was examined.Result and discussionMicelles were successfully formed with appropriate characteristics and smaller sizes than 20 nm. The Poly Dispersity Index (PDI), zeta potential, encapsulation efficacy of micelles was 0.227, - 22 mV, 81%, respectively. Also, the stability of nano micelles was higher in SGF as compared to SIF. Our outcomes of TNF-a, IL-1B, and MDA evaluation show a significant ameliorating effect of the Berberine (BBR) and BBR-loaded micelles in pretreated groups.ConclusionOur experimental data show that pretreated groups in different doses (nano BBR 100, 75, 50 mg/kg, and BBR 100 mg/kg) successfully showed decreased levels of the inflammatory factors in cerebral ischemia compared with the stroke group and pretreated group with nano BBR in the dose of 25 mg/kg. Nano BBR formulation with a lower dose can be a better candidate than conventional BBR formulation to reduce oxidative and inflammatory factors in cerebral ischemia. Therefore, BBR-loaded micelle formulation could be a promising protective agent on cerebral ischemia.
| S-EPMC8487542 | biostudies-literature
Project description:Since the first description of the possible utilization of the internal maxillary artery for bypass surgery, there are some reports of its use in aneurysm cases; however, there is no information about the possible advantages of this type of bypass for cerebral ischemic disease. We present a 77-year-old man with a history of diabetes, hypertension, systemic atherosclerosis, and two acute myocardial infarctions with left hemiparesis. Imaging studies reported total occlusion of the right internal carotid artery and 75% occlusion on the left side, with an old opercular infarction and repeated transient ischemic attacks in the right middle cerebral artery territory despite medical treatment. After a consensus, we decided to perform a bypass from the internal maxillary artery to the M2 segment of the middle cerebral artery using a radial artery graft. After performing the proximal anastomosis, the calculated graft's free flow was 216 ml/min. Subsequently, after completing the bypass, the patency was confirmed with fluorescein videoangiography and intraoperative Doppler. Postoperatively, imaging studies showed improvement in the perfusion values and the hemiparesis from 3/5 to 4+/5. The patient was discharged one week after the operation, with a modified Rankin scale of 1, without added deficits. The use of revascularization techniques in steno-occlusive disease indicates a select group of patients that may benefit from this procedure. In addition, internal maxillary artery bypass has provided a safe option for large areas of ischemia that cannot be supplied with a superficial temporal artery - middle cerebral artery bypass.
| S-EPMC10995475 | biostudies-literature
Project description:Various surgical treatments are available for occlusive subclavian and common carotid artery diseases. Nevertheless, to date, when cerebral endovascular treatment is utilized, revascularization via direct surgery may be required. This study reported five symptomatic cases of revascularization for CCA and SCA occlusive and stenotic lesions that were expected to be challenging to treat with endovascular treatment. We performed subclavian artery-common carotid artery or internal carotid artery bypass using artificial blood vessels or saphenous vein grafts in five patients with subclavian steal syndrome, symptomatic common carotid artery occlusion, and severe proximal common carotid artery stenosis. In this study, good bypass patency was achieved in all five cases. Although there were no intraoperative complications, one patient had a postoperative lymphatic leak. Moreover, there was no recurrence of stroke during postoperative follow-up for an average of 2 years. Conclusively, subclavian artery-common carotid artery bypass can be an effective surgical treatment for common carotid artery occlusion, proximal common carotid artery stenosis, and subclavian artery occlusion.
| S-EPMC10325775 | biostudies-literature