scholarly journals LDH and PDH Activities in the Ischemic Brain and the Effect of Reperfusion—An Ex Vivo MR Study in Rat Brain Slices Using Hyperpolarized [1-13C]Pyruvate

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 210
Author(s):  
Gal Sapir ◽  
David Shaul ◽  
Naama Lev-Cohain ◽  
Jacob Sosna ◽  
Moshe J. Gomori ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Tissue ◽  
Baseline Level ◽  
Activity Ratio ◽  
Brain Slices ◽  
High Energy ◽  
Imaging Biomarkers ◽  
Ischemic Insult ◽  
Ischemic Brain ◽  
The Status

Ischemic stroke is a leading cause for neurologic disability worldwide, for which reperfusion is the only available treatment. Neuroimaging in stroke guides treatment, and therefore determines the clinical outcome. However, there are currently no imaging biomarkers for the status of the ischemic brain tissue. Such biomarkers could potentially be useful for guiding treatment in patients presenting with ischemic stroke. Hyperpolarized 13C MR of [1-13C]pyruvate is a clinically translatable method used to characterize tissue metabolism non-invasively in a relevant timescale. The aim of this study was to utilize hyperpolarized [1-13C]pyruvate to investigate the metabolic consequences of an ischemic insult immediately during reperfusion and upon recovery of the brain tissue. The rates of lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were quantified by monitoring the rates of [1-13C]lactate and [13C]bicarbonate production from hyperpolarized [1-13C]pyruvate. 31P NMR of the perfused brain slices showed that this system is suitable for studying ischemia and recovery following reperfusion. This was indicated by the levels of the high-energy phosphates (tissue viability) and the chemical shift of the inorganic phosphate signal (tissue pH). Acidification, which was observed during the ischemic insult, has returned to baseline level following reperfusion. The LDH/PDH activity ratio increased following ischemia, from 47.0 ± 12.7 in the control group (n = 6) to 217.4 ± 121.3 in the ischemia-reperfusion group (n = 6). Following the recovery period (ca. 1.5 h), this value had returned to its pre-ischemia (baseline) level, suggesting the LDH/PDH enzyme activity ratio may be used as a potential indicator for the status of the ischemic and recovering brain.

Effects of near-far acupuncture on neuronal function and expression of apoptosis-related protein Bax/Bcl-2/Cleaved caspase-3 in rats with ischemic stroke

2021 ◽  
Vol 45 (2) ◽  
pp. 73-86
Author(s):  
Wang Jian ◽  
Zhang Can ◽  
Yang Jun ◽  
Xing Liwei ◽  
Zhang Kun ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Brain Tissue ◽  
Caspase 3 ◽  
Neurological Function ◽  
Acupuncture Group ◽  
Sham Operation ◽  
Model Group ◽  
Ischemic Brain ◽  
Ischemic Brain Tissue

Objectives To explore the effects of electroacupuncture on nerve function in rats with ischemic stroke and its mechanism of anti-apoptosis. Methods A total of 80 SPF male SD rats were randomly divided into sham operation group, model group, sham electroacupuncture group, acupuncture group, electroacupuncture group and 16 rats in each group. The rat model of left ischemic stroke was prepared by suture embolization. In the sham group, the left common carotid artery was isolated only and no other treatment was given. In the electroacupuncture group, "Baihui" and "Mingmen" were selected for acupuncture, followed by dilatation wave, frequency 2Hz/100Hz, intensity 1mA, and electroacupuncture for 30min. The sham electroacupuncture group was the same as the electroacupuncture group in acupoint electroacupuncture group was the same as the electroacupuncture group in acupoint selection. The electroacupuncture group was only inserted subcutaneously and then connected with the electroacupuncture group without power supply, and fixed for 30 minutes. The electroacupuncture group and the acupuncture group received electroacupuncture treatment once, for a total of 14 days, 1d after modeling. The Improved Neurological Impairment scale (mNSS) was used to evaluate the degree of neurological impairment in each group after anesthesia and wakefulness. The percentage of cerebral infarction area was determined by TTC staining. HE staining and Nissl staining were used to observe the pathological changes of ischemic brain tissue. The level of apoptosis in ischemic brain tissue was detected by TUNEL assay. Western blot was used to detect protein expression of Bax, Bcl-2 and Cleaved caspase-3 in ischemic brain tissue. Results Compared with the sham operation group, neurological function score, percentage of cerebral infarction area and apoptosis level in the model group were significantly increased (all P < 0.01). Compared with the model group, neurological function score, percentage of cerebral infarction area and apoptosis index of acupuncture group and electroacupuncture group were decreased (all P <0.05). Compared with the model group, the expression levels of Bcl-2 protein in ischemic brain tissue of rats with ischemic stroke were up-regulated in the acupuncture group and electroacupuncture group to different degrees, while the expression levels of Bax and Cleaved caspase-3 protein were down-regulated in the electroacupuncture group. Conclusion Electroacupuncture may inhibit Bax, Cleaved caspase-3 and up-regulate the expression of Bcl-2 against neuronal apoptosis, thereby improving the neurological function injury of ischemic stroke rats.

scholarly journals A dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke to the sensorimotor cortex in middle aged male and female mice

2021 ◽  
Author(s):  
Gyllian B Yahn ◽  
Brandi Wasek ◽  
Teodoro Bottiglieri ◽  
Olga Malysheva ◽  
Marie A Caudill ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vitamin B12 ◽  
Brain Tissue ◽  
Neuronal Survival ◽  
Vitamin B12 Deficiency ◽  
Ischemic Brain ◽  
Male And Female ◽  
Female Mice ◽  
Ischemic Brain Tissue ◽  
B12 Deficiency

The majority of the population is growing older, in 2000, 10% of the total population of the world was over 60 years old and the proportion is projected to increase to 21% by 2050. Currently, ischemic stroke predominately affects the elderly. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, most older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin that take place during the aging process. Using a mouse model system, we investigated the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in ischemic versus non-ischemic brain tissue. At 10-weeks of age male and female C57Bl/6J mice were put on control or vitamin B12 deficient diets for 4-weeks prior to ischemic damage. At 14 weeks of age, we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model. Animals were continued on diets for 4 weeks after damage. At 18 weeks of age, we assessed stroke outcome using the accelerating rotarod and forepaw placement tasks. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissues to assess histological and biochemical measurements. All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to control diet animals after ischemic stroke. In ischemic brain tissue no difference between groups in lesion volume was observed. More neuronal survival was present in ischemic brain tissue of the vitamin B12 deficient group compared to controls. There were changes in choline metabolites in ischemic brain tissue as a result of diet and sex. In conclusion, the data presented in this study confirms that a vitamin B12 deficiency impacts motor function in older adult male and female mice after ischemic stroke. The mechanisms driving this change may be a result of neuronal survival and compensation in choline metabolism within the damaged brain tissue.

scholarly journals Receptor for Advanced Glycation End Products Is Involved in LPA5-Mediated Brain Damage after a Transient Ischemic Stroke

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 80
Author(s):  
Arjun Sapkota ◽  
Sung Jean Park ◽  
Ji Woong Choi
Keyword(s):  
Ischemic Stroke ◽  
Advanced Glycation End Products ◽  
Brain Injuries ◽  
Artery Occlusion ◽  
Advanced Glycation ◽  
Ischemic Brain ◽  
Blood Brain Barrier Disruption ◽  
Glycation End Products ◽  
End Products ◽  
Ischemic Core

Lysophosphatidic acid receptor 5 (LPA5) has been recently identified as a novel pathogenic factor for brain ischemic stroke. However, its underlying mechanisms remain unclear. Here, we determined whether the receptor for advanced glycation end products (RAGE) could be involved in LPA5-mediated brain injuries after ischemic challenge using a mouse model of transient middle cerebral artery occlusion (tMCAO). RAGE was upregulated in the penumbra and ischemic core regions after tMCAO challenge. RAGE upregulation was greater at 3 days than that at 1 day after tMCAO challenge. It was mostly observed in Iba1-immunopositive cells of a post-ischemic brain. Suppressing LPA5 activity with its antagonist, TCLPA5, attenuated RAGE upregulation in the penumbra and ischemic core regions, particularly on Iba1-immunopositive cells, of injured brains after tMCAO challenge. It also attenuated blood–brain barrier disruption, one of the core pathogenesis upon RAGE activation, after tMCAO challenge. As an underlying signaling pathways, LPA5 could contribute to the activation of ERK1/2 and NF-κB in injured brains after tMCAO challenge. Collectively, the current study suggests that RAGE is a possible mediator for LPA5-dependent ischemic brain injury.

Post-ischemic brain tissue alkalosis suppressed by U74006F

1993 ◽  
Vol 114 (1) ◽  
pp. 36-39 ◽  
Author(s):  
Ana M.Q.Vande Linde ◽  
Michael Chopp ◽  
Sue Ann Lee ◽  
Lonni R. Schultz ◽  
K.M.A. Welch
Keyword(s):  
Brain Tissue ◽  
Ischemic Brain ◽  
Ischemic Brain Tissue

scholarly journals REVIEW OF THE PHENOMENOLOGY OF NONCOMMUTATIVE GEOMETRY

2004 ◽  
Vol 19 (02) ◽  
pp. 179-204 ◽  
Author(s):  
I. HINCHLIFFE ◽  
N. KERSTING ◽  
Y. L. MA
Keyword(s):  
Electric Dipole ◽  
Particle Physics ◽  
Extra Dimensions ◽  
Linear Collider ◽  
Dipole Moments ◽  
High Energy ◽  
Low Energy ◽  
Electric Dipole Moments ◽  
The Status ◽  
High Energy Scattering

We present a pedagogical review of particle physics models that are based on the noncommutativity of space–time, [Formula: see text], with specific attention to the phenomenology these models predict in particle experiments either in existence or under development. We summarize results obtained for high energy scattering such as would occur, for example, in a future e+e-linear collider with [Formula: see text], as well as low energy experiments such as those pertaining to elementary electric dipole moments and other CP violating observables, and finally comment on the status of phenomenological work in cosmology and extra dimensions.

Protective effect of Saccharomyces cerevisiae in Rattus norvegicus Ischemic Stroke Model

2021 ◽  
pp. 5785-5789
Author(s):  
Dedy Budi Kurniawan ◽  
Mokhamad Fahmi Rizki Syaban ◽  
Arinal Mufidah ◽  
Muhammad Unzila Rafsi Zulfikri ◽  
Wibi Riawan
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ischemic Stroke ◽  
Brain Tissue ◽  
Tissue Injury ◽  
Intervention Group ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Hematopoietic Stem ◽  
The Brain

Stroke is one of the leading causes of morbidity and mortality in all ages. Ischemic stroke activates excitotoxic glutamate cascade leading to brain tissue injury. Saccharomyces cerevisiae is a unicellular yeast widely found in nature. S. cerevisiae is neuroprotective and able to increase the differentiation of hematopoietic stem cells (HSCs) into neuronal cells. it may increase levels of neuroprotectant BDNF in the brain tissue, therefore increase the protection of neurons. BDNF may prevent glutamate-driven excitotoxicity by reducing glutamate levels. This study uses a randomized post-test only controlled group design. In this in vivo study, rodent models of ischemic stroke were divided into five groups comprising of the negative control group, positive control group, intervention group 1 (18mg/kgBW), intervention group 2 (36mg/kgBW) and intervention group 3 (72 mg/kgBW). Groups treated with Saccharomyces cerevisiae extract showed significantly increased BDNF levels in the brain tissue, and the expression of the glutamate level was significantly reduced (P <0.05) compared to the positive control group. Thus Saccharomyces cerevisiae has a promising potential to become a therapy against ischemic stroke disease. however further research is needed regarding the efficacy and toxicity of Saccharomyces cerevisiae.

Abstract 3268: Ct Perfusion As A Tool To Predict The Risk Of Hemorrhagic Transformation In Ischemic Stroke Treated With Tissue Plasminogen Activator: A Single Center Experience.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tareq Kass-Hout ◽  
Maxim Mokin ◽  
Omar Kass-Hout ◽  
Emad Nourollahzadeh ◽  
David Wack ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Brain Tissue ◽  
Cerebral Blood Volume ◽  
Ct Perfusion ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Stroke Therapy ◽  
Two Phase ◽  
The Mean

Objective: To use the Computed Tomography Perfusion (CTP) parameters at the time of hospital admission, including Cerebral Blood Volume (CBV) and Permeability Surface area product (PS), to identify patients with higher risk to develop hemorrhagic transformation in the setting of acute stroke therapy with intravenous thrombolysis. Methods: Retrospective study that compared admission CTP variables between patients with Hemorrhagic Transformation (HT) acute stroke and those with no hemorrhagic transformation. Both groups received standard of care intravenous thrombolysis with tPA. Twenty patients presented to our stroke center between the years 2007 - 2011 within 3 hours after stroke symptoms onset. All patients underwent two-phase 320 slice CTP which creates CBV and PS measurements. Patients were divided into two groups according to whether or not they had HT on a follow up CT head without contrast, done within 36 hours of the thrombolysis therapy. Clinical, demographic and CTP variables were compared between the HT and non-HT groups using logistic regression analyses. Results: HT developed in 8 (40%) patients. Patients with HT had lower ASPECT score ( P =.03), higher NIHSS on admission ( P= .01) and worse outcome ( P= .04) compared to patients who did not develop HT. Baseline blood flow defects were comparable between the two groups. The mean PS for the HT group was 0.53 mL/min/100g brain tissue, which was significantly higher than that for the non-HT group of 0.04 mL/min/100g brain tissue ( P <.0001). The mean area under the curve was 0.92 (95% CI). The PS threshold of 0.26 mL/min/100g brain tissue had a sensitivity of 80% and a specificity of 92% for detecting patients with high risk of hemorrhagic transformation after intravenous thrombolysis. Conclusions: Admission CTP measurements might be useful to predict patients who are at higher risk to develop hemorrhagic transformation after acute ischemic stroke therapy.

Abstract 61: MR Perfusion to Determine the Status of Collaterals in Patients With Acute Ischemic Stroke: Look Beyond Perfusion Time-maps

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kambiz Nael ◽  
James Knitter ◽  
Amish Doshi ◽  
J Mocco ◽  
Thomas Naidich
Keyword(s):  
Ischemic Stroke ◽  
Diagnostic Accuracy ◽  
Cerebral Angiography ◽  
Independent Predictor ◽  
Collateral Flow ◽  
Mr Perfusion ◽  
The Status ◽  
Perfusion Time ◽  
Sensitivity Specificity ◽  
Angiographic Findings

Purpose: Collateral flow is an independent predictor of reperfusion and infarct size in patients with acute ischemic stroke (AIS). MR perfusion time-maps show delayed perfusion but unable to differentiate antegrade from collateral flow if used alone. Using a multiparametric approach, we aimed to identify a perfusion biomarker that can represent the extent of collaterals in comparison to angiographic findings. Methods: AIS patients with MCA proximal occlusion who had baseline MRI and cerebral angiography included. MR perfusion data were processed by Bayesian method to generate arterial tissue delay (ATD) maps at thresholds of 2 & 6 seconds. The volume of delayed perfusion (Vol-ATD 2sec ), critical hypoperfusion (Vol-ATD 6sec ), and hypoperfusion (Vol-ATD 2sec-6sec ) in addition to corresponding rCBV and rCBF were calculated. Baseline angiography collaterals were dichotomized to poor (TICI ≤2a) or good collaterals (TICI≥ 2b). The association of perfusion biomarkers and status of collaterals was assessed by repeated measure of analyses and receiver operating characteristic (ROC) to determine the optimal parameters for predicting the status of collaterals. Results: In 37 patients included, 20 had good collaterals on cerebral angiography. After controlling for age, baseline NIHSS and infarct volume, multivariate logistic regression analysis identified rCBV (p=0.001) and hypoperfused volume (Vol-ATD 2sec-6sec ), but not rCBF, Vol-ATD 2sec or Vol-ATD 6sec , as independent predictors of good collaterals. ROC analysis showed AUC of 0.89 (sensitivity/specificity: 85%90%) for rCBV and AUC of 0.78 (sensitivity/specificity: 70%82%) for Vol-ATD 2sec-6sec . Hypoperfused tissue volume (Vol-ATD 2sec-6sec ) x its rCBV, termed hypoperfused tissue collateral index , remained an independent predictor of good collaterals with improved diagnostic accuracy over each measure alone (AUC: 0.96, sensitivity/specificity: 91%100%). Conclusions: Multiparametric MR perfusion can be used to assess the status of collaterals in patients with AIS. Hypoperfused tissue collateral index defined as hypoperfused volume (Vol-ATD 2sec-6sec ) x rCBV is a new perfusion index with diagnostic accuracy of 96% compared to angiographic findings to predict status of collaterals.

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