Some new prospects in the understanding of the molecular basis of the pathogenesis of stroke

Saeed, Sheikh A.; Shad, Kaneez Fatima; Saleem, Taimur; Javed, Faisal; Khan, Muhammad Sikander Ghayas

doi:10.1007/s00221-007-1050-9

Cited by 114 publications

(73 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is assumed that oxidative stress contributes to the initiation and development of stroke via different interrelated mechanisms [43]. Oxidative stress has a profound effect in stroke pathogenesis due to the high susceptibility of the brain to ROS-induced damage [44]. Independent of the mechanisms responsible for ischemic stroke, ischemia causes a cascade of events via different pathways that increase ROS production.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Thioredoxin Are Associated with Stroke Risk, Severity, and Lesion Volumes

et al. 2014

View full text Add to dashboard Cite

Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in Chinese patients with acute ischemic stroke (AIS). From January 1, 2012, to December 31, 2013, all patients with first-ever acute ischemic stroke were recruited to participate in the study. Serum levels of TRX were assayed with solid-phase sandwich enzyme-linked immunosorbent assay (ELISA), and the severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. The results indicated that the median serum TRX levels were significantly (P < 0.0001) higher in stroke patients as compared to normal cases [15.03 ng/mL (interquartile range (IQR), 10.21-32.42) and 8.95 ng/mL (6.79-11.05), respectively]. We found the serum TRX reflected the disease severity of AIS. There was a significant positive association between serum TRX levels and NIHSS scores (r = 0.476, P < 0.0001). After adjusting for all other possible covariates, TRX remained as an independent marker of AIS with an adjusted OR of 1.245 (95 % confidence interval (CI), 1.164-1.352; P < 0.0001). Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum TRX levels as an indicator for auxiliary diagnosis of AIS was projected to be 11.0 ng/mL, which yielded a sensitivity of 80.3 % and a specificity of 73.7 %, with the area under the curve at 0.807 (95 % CI, 0.766-0.847). Further, in our study, we found that an increased risk of AIS was associated with serum TRX levels ≥11.0 ng/mL (adjusted OR 6.99; 95 % CI, 2.87-12.87) after adjusting for possible confounders. Our study demonstrated that serum TRX levels at admission were associated with stroke severity and lesion volumes. Elevated levels could be considered as a novel, independent diagnosis marker of AIS in a Chinese sample.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum Levels of Thioredoxin Are Associated with Stroke Risk, Severity, and Lesion Volumes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Inflammation can extend ischemic injury (20) to adversely affect stroke outcome (21) and may provide new therapeutic targets to treat patients outside of the narrow thrombolysis window of 3-6 h. For example, in a recent study it was shown that the administration of the drug AM-36, a Na ϩ channel blocker and an antioxidant, Histopathological analyses correspond to MPO imaging findings. (A) MPO imaging on day 3 after infarction shows a large area of enhancement in the basal ganglia and cerebral cortex.…”

Section: Discussionmentioning

confidence: 99%

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Breckwoldt

Chen

Stangenberg³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

280

240

View full text Add to dashboard Cite

Inflammation can extend ischemic brain injury and adversely affect outcome in experimental animal models. A key difficulty in translating animal studies to humans is the lack of a definitive method to confirm and track inflammation in the brain in vivo. Myeloperoxidase (MPO), a key inflammatory enzyme secreted by activated neutrophils and macrophages/microglia, can generate highly reactive oxygen species to cause additional damage in cerebral ischemia. We report here that a functional, enzyme-activatable MRI agent can accurately track the oxidative activity of MPO noninvasively in stroke in living animals. We found that MPO is widely distributed in ischemic tissues, correlates positively with infarct size, and is detected even 3 weeks postinfarction. The peak level of MPO activity, determined by activation of the MPO-sensing agent in vivo and confirmed by MPO activity and quantitative RT-PCR assays, occurred on day 3 after ischemia. Both neutrophils and macrophages/microglia contribute to secrete MPO in the ischemic brain, although neutrophils peak earlier (days 1-3) whereas macrophages/microglia are most abundant later (days 3-7). In contrast to the conventional MRI agent diethylenetriaminepentatacetate gadolinium, which reports blood-brain barrier disruption, MPO imaging is able to additionally track MPO activity and confirm inflammation on the molecular level in vivo, information that was previously only possible to obtain on ex vivo brain sections and impossible to assess in living human patients. Our findings could allow efficient noninvasive serial screening of therapies targeting inflammation and the use of MPO imaging as an imaging biomarker to risk-stratify patients.inflammation ͉ ischemia ͉ molecular imaging ͉ MRI ͉ brain

show abstract

“…ROS have significant cellular effects including lipid peroxidation, protein denaturation, inactivation of enzymes, nucleic acid and DNA damage, release of Ca 2+ from intracellular stores, damage to the cytoskeletal structure and chemotaxis. [28][29][30] On the other hand, MMP loss causes the release of apoptosis-inducing factors and generates secondary ROS, 31) and, as a result, ultimately leads to cell death. The research displayed that H 2 O 2 led to ROS production while ginkgolide K-pretreated significantly attenuated ROS level.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Ginkgolide K against H<sub>2</sub>O<sub>2</sub>-Induced PC12 Cell Cytotoxicity by Ameliorating Mitochondrial Dysfunction and Oxidative Stress

Liu

Xun

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Mitochondria and oxidative stress play important roles in neuronal cell death associated with cerebral ischemia. Elevated level of reactive oxygen species (ROS) and mitochondrial dysfunction are thought to be responsible for cerebral ischemia injury along with neural cells death through several apoptotic mechanisms. In this study, exposure of rat pheochromocytoma (PC12) cells to hydrogen peroxide (H 2 O 2 ) at the concentration of 0.3 mM for 24 h caused significant loss of cell viability, lactate dehydrogenase (LDH) release from cells, ascent of ROS level and mitochondrial membrane potential (MMP) decrease. Moreover, the activities of caspase-9, caspase-8 and caspase-3 all were increased in H 2 O 2 -induced PC12 cells. However, pretreatment with ginkgolide K (GK) solutions of different concentrations (10, 50, 100 µM) for 24 h prior to exposuring to H 2 O 2 significantly increased cells viability, suppressed LDH release, attenuated ROS level, prevented cytochrome c release from mitochondria and boosted MMP expression. In addition, ginkgolide K notably inhibited the caspase-3 and caspase-9 but not caspase-8 activities in exogenous H 2 O 2 -treated PC12 cells. These results demonstrated that ginkgolide K protected PC12 cells from H 2 O 2 -induced apoptosis by restoring MMP expression, ameliorating oxidative stress and subsequently leading to inhibit the activity of caspase-3 protein. Therefore, the present study supported that ginkgolide K may be a promising neuroprotective compound for cerebral ischemia treatment.

show abstract

Some new prospects in the understanding of the molecular basis of the pathogenesis of stroke

Cited by 114 publications

References 53 publications

Serum Levels of Thioredoxin Are Associated with Stroke Risk, Severity, and Lesion Volumes

Serum Levels of Thioredoxin Are Associated with Stroke Risk, Severity, and Lesion Volumes

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Neuroprotective Effect of Ginkgolide K against H<sub>2</sub>O<sub>2</sub>-Induced PC12 Cell Cytotoxicity by Ameliorating Mitochondrial Dysfunction and Oxidative Stress

Contact Info

Product

Resources

About