Hyperglycemia increased brain ischemia injury through extracellular signal-regulated protein Kinase
Institute of Immunopathology, School of Life Science & Technology, Xi'an Jiaotong University, Xi'an 710061, China. Pathology - Research and Practice
(Impact Factor: 1.4).
02/2006; 202(1):31-6. DOI: 10.1016/j.prp.2005.10.002
This study was to examine the alterations in the phosphorylation of mitogen-activated protein kinase (MAPK) family in transient brain ischemia under a hyperglycemia and to highlight the molecular mechanisms by which hyperglycemia exacerbates brain damage resulting from stroke. Extracellular signal-regulated protein kinase (ERK) expression was studied in rats subjected to global brain ischemia with pre-ischemic normoglycemic (CIN) and hyperglycemic (CIH) conditions. In another group, the hyperglycemic ischemic rats were pretreated with ERK inhibitor U0126 (U0126). Increased phospho-ERK1/2 immunoreactive neurons in the cingulate cortex and hippocampal CA3 were detected in CIN after ischemia and reperfusion. The numbers of phospho-ERK1/2-positive neurons were further increased significantly in CIH compared to the CIN. Pretreatment with U0126 in CIH rats significantly decreased ERK1/2 immunoreactive cells. Western blot analyses confirmed that phospho-ERK1/2 increased significantly after 30 min ischemia and reperfusion compared to non-ischemic controls in both the CIN and CIH groups. The increase of phospho-ERK1/2 was more prominent in the CIH than in the CIN group after 3 and 6h of reperfusion. Treatment with U0126 significantly reduced phospho-ERK1/2 in the CIH group. The findings presented here suggest that ERK1/2 may play a role in mediating neuronal cells death under hyperglycemic condition.
Available from: Yue Chang
- "Previous studies have demonstrated that hyperglycemia markedly increased phosphorylation of ERK 1/2 in the cingulated cortex and hippocampal CA3 and dentate gyrus areas, structures that are recruited and exacerbated by hyperglycemia when subjected a transient forebrain ischemia (Li et al., 2001; Krupinski et al., 2005; Kurihara et al., 2004). While increased phosphorylation of ERK1/2 may promote cell survival by increasing cell proliferation in vitro, inhibition of the ERK1/2 has been linked to decrease neuronal cell death after transient focal cerebral ischemia under normoglycemic conditions and after transient forebrain ischemia under hyperglycemic conditions (Namura et al., 2001; Zhang et al., 2006). In this study, we observed that GM1 treatment significantly suppressed the phosphorylation of ERK1/2, a critical member in the MAPK family. "
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ABSTRACT: Monosialotetrahexosy-1 ganglioside (GM1) has been shown to reduce brain damage induced by cerebral ischemia. The objective of this study is to determine whether GM1 is able to ameliorate hyperglycemia-exacerbated ischemic brain damage in hyperglycemia-recruited areas such as the hippocampal CA3 sub regions and the cingulated cortex. Histologic stainings of Haematoxylin and Eosin, Nissl body, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and phospho-ERK1/2 were performed on brain sections that have been subjected to 15 min of forebrain ischemia with reperfusion of 0, 1, 3, and 6h in normoglycemic, hyperglycemic and GM1-pretreated hyperglycemic groups. The results showed that GM1 ameliorated ischemic neuronal injuries in the CA3 area and cingulated cortex of the hyperglycemic animals after ischemia and reperfusion. Immunohistochemistry of phospho-ERK1/2 revealed that the neuroprotective effects of GM1 were associated with suppression of phospho-ERK1/2. The results suggest that GM1 attenuates diabetic-augmented ischemic neuronal injuries probably through suppression of ERK1/2 phosphorylation.
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ABSTRACT: In this review, we summarize the role of hyperglycemia during cerebral ischemia. Hyperglycemia occurring during experimental and clinical stroke has been associated with increased cerebral damage. Increased oxidative stress resulting from hyperglycemia is believed to contribute to the exacerbated damage. More specifically, superoxide, nitric oxide and peroxynitrite are believed to play an important role in cerebral damage. This also involves increased recruitment of various blood cells to the ischemic zone that contribute to inflammation. We present data from our group and others that demonstrate that free radical production is increased during hyperglycemic stroke in rodents. Recent data suggest that inflammation is an important component of ischemic damage under both normo- and hyperglycemic conditions. We summarize numerous studies that indicate that a variety of antioxidant (inhibition of free radical production, scavenging of free radicals and increasing free radical degradation) and anti-inflammatory strategies decrease cerebral infarction. Finally, we compare the success of some of these strategies in clinical trials compared to the animal models.
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ABSTRACT: Hyperglycemia is a common problem in newborns undergoing intensive care, especially extremely low birth weight (ELBW) infants. There is a lack of consensus with regard to various aspects of management of neonatal hyperglycemia including definition, optimal management strategy as well as short and long term implications. We reviewed the current evidence in this regard. Recent studies suggest that adequate control of hyperglycemia may be beneficial but long-term implications of hyperglycemia and insulin therapy in the ELBW infants are not known. Awaiting further research, it may be pragmatic to use a more operational definition of hyperglycemia and limit insulin therapy to neonates with high risk of osmolar derangement as per the proposed guideline.
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