Purinergic Receptor Stimulation Decreases Ischemic Brain Damage by Energizing Astrocyte Mitochondria

Sayre, N.; Chen, Yanan; Sifuentes, Mikaela; Stoveken, Brian J; Lechleiter, James D.

doi:10.1007/978-3-319-08894-5_7

Cited by 10 publications

(7 citation statements)

References 189 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A lowered release of glucose from the liver would cause even less glucose to reach the vulnerable portions of the stroke lesions À a region termed the ''penumbra'' which can expand as a lesion grows. 32 Another relevant observation first reported by Bing et al is that liver damage occurs in a middle cerebral artery occlusion rat model. 33 Consequently, etomoxir treatments might be expected to exacerbate any complications with liver function, and further increase the morbidity associated with stroke.…”

Section: Discussionmentioning

confidence: 88%

Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage

Sayre

Sifuentes

Holstein

et al. 2016

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

We previously demonstrated that stimulation of astrocyte mitochondrial ATP production via P2Y 1 receptor agonists was neuroprotective after cerebral ischemic stroke. Another mechanism that increases ATP production is fatty acid oxidation (FAO). We show that in primary human astrocytes, FAO and ATP production are stimulated by 3,3,5 triiodo-L-thyronine (T3). We tested whether T3-stimulated FAO enhances neuroprotection, and show that T3 increased astrocyte survival after either hydrogen peroxide exposure or oxygen glucose deprivation. T3-mediated ATP production and protection were both eliminated with etomoxir, an inhibitor of FAO. T3-mediated protection in vitro was also dependent on astrocytes expressing HADHA (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase), which we previously showed was critical for T3-mediated FAO in fibroblasts. Consistent with previous reports, T3-treatment decreased stroke volumes in mice. While T3 decreased stroke volume in etomoxir-treated mice, T3 had no protective effect on stroke volume in HADHA þ/À mice or in mice unable to upregulate astrocyte-specific energy production. In vivo, 95% of HADHA co-localize with glial-fibrillary acidic protein, suggesting the effect of HADHA is astrocyte mediated. These results suggest that astrocyte-FAO modulates lesion size and is required for T3-mediated neuroprotection post-stroke. To our knowledge, this is the first report of a neuroprotective role for FAO in the brain.

show abstract

Section: Discussionmentioning

confidence: 88%

Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage

Sayre

Sifuentes

Holstein

et al. 2016

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, Cit supplementation was also demonstrated to be neuroprotective through modulating nitric oxide generation (26). Coincidently, these two mechanisms were all involved in rescuing mitochondrial functions, indicating that mitochondrial damage might be a very early event in ischemic stroke and an early sensitive response to hypoxia (27). The increased Ala and Cit in CI were thought to be the protective response of the body in acute phase.…”

Section: Discussionmentioning

confidence: 98%

Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis

Zhu

Cao

et al. 2016

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty-nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5-OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above-mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation.

show abstract

“…In the present study, retinal ischemia caused marked activation of microglia and astrocytes in terms of their protein intensities, morphological changes, increased number and migration throughout retinal cell layers, whereas activation of these glial cells were significantly inhibited by the systemic treatment with P 6 Q peptide. The roles of microglia and astrocytes are complex due to their detrimental and beneficial actions in ischemia (Barreto et al, 2011;Gomes-Leal, 2012;Taylor and Sansing, 2013;Sayre et al, 2014;Hirayama et al, 2015). We previously demonstrated that ProTα protects the brain and retina from ischemic damage, through up-regulation of brain-derived neurotrophic factor (BDNF) or erythropoietin (EPO) (Fujita and Ueda, 2007;Fujita et al, 2009;Ueda et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective impact of prothymosin alpha-derived hexapeptide against retinal ischemia–reperfusion

et al. 2016

View full text Add to dashboard Cite

Prothymosin alpha (ProTα) has robustness roles against brain and retinal ischemia or serum-starvation stress. In the ProTα sequence, the active core 30-amino acid peptide/P30 (a.a.49-78) is necessary for the original neuroprotective actions against ischemia. Moreover, the 9-amino acid peptide sequence/P9 (a.a.52-60) in P30 still shows neuroprotective activity against brain and retinal ischemia, though P9 is less potent than P30. As the previous structure-activity relationship study for ProTα may not be enough, the possibility still exists that any sequence smaller than P9 retains potent neuroprotective activity. When different P9- and P30-related peptides were intravitreally injected 24h after retinal ischemia in mice, the 6-amino acid peptide/P6 (NEVDEE, a.a.51-56) showed potent protective effects against ischemia-induced retinal functional deficits, which are equipotent to the level of P30 peptide in electroretinography (ERG) and histological damage in Hematoxylin and Eosin (HE) staining. Further studies using ERG and HE staining suggested that intravitreal or intravenous (i.v.) injection with modified P6 peptide/P6Q (NEVDQE) potently inhibited retinal ischemia-induced functional and histological damage. In an immunohistochemical analysis, the ischemia-induced loss of retinal ganglion, bipolar, amacrine and photoreceptor cells were inhibited by a systemic administration with P6Q peptide 24h after the ischemic stress. In addition, systemic post-treatment with P6Q peptide significantly inhibited retinal ischemia-induced microglia and astrocyte activation in terms of increased ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) intensity, respectively, as well as their morphological changes, increased number and migration. Thus, this study demonstrates the therapeutic significance of modified P6 peptide P6Q (NEVDQE) derived from 6-amino acid peptide (P6) in ProTα against ischemic damage.

show abstract

Purinergic Receptor Stimulation Decreases Ischemic Brain Damage by Energizing Astrocyte Mitochondria

Cited by 10 publications

References 189 publications

Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage

Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage

Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis

Neuroprotective impact of prothymosin alpha-derived hexapeptide against retinal ischemia–reperfusion

Contact Info

Product

Resources

About