Activation of the extracellular signal-regulated protein kinase cascade in the hippocampal CA1 region in a rat model of global cerebral ischemic preconditioning
Section snippets
Experimental groups
The experimental designs for histopathological, western blot, and immunohistochemical analyses are shown in Fig. 1A, B and C, respectively. The different experimental groups and the number of animals in each group are indicted in Table 1. Animals in the nonconditioned and preconditioned groups were subjected to sham surgery and 3 min of ischemia, respectively, followed by two days of recovery, and then subjected to 9 min of ischemia. Both non-conditioned and preconditioned groups were allowed a
Histopathological outcome after preconditioning ischemia
There was no significant difference in blood PO2, PCO2, mean arterial blood pressure, blood pH or blood glucose values between preconditioned and non-conditioned groups, when recorded prior to, during, and after ischemic insults or sham surgery (data not shown).
Seven days after 3 min of preconditioning ischemia there were only a few degenerated neurons in the CA1 region. After two months of reperfusion there was no statistical difference between the number of neurons in the 3-min ischemia group
Discussion
The main findings of this study are that (i) the MEK1/2 becomes phosphorylated during reperfusion after 3 min of preconditioning ischemia. At day two of reperfusion both MEK1/2 and ERK1/2 remain phosphorylated; (ii) that the MEK1/2 and ERK1/2 are persistently phosphorylated in nonconditioned brains after the second ischemic insult, whereas transiently phosphorylated in preconditioned brains. Below we will discuss the effects of preconditioning on the ERK signaling cascade in the rat CA1 region
Conclusions
Our results demonstrate that ischemic preconditioning leads to a prolonged and persistent activation of the ERK cascade after preconditioning ischemia and to a normalization of cell signaling after the second ischemic insult. We speculate that preconditioning ischemia protects CA1 neurons against a subsequent ischemic insult, by activating mechanisms which induce regulatory and protective proteins, and down-regulate detrimental cell signaling.
Acknowledgements
The authors wish to thank Ulrika Sparrhult for excellent technical assistance. This work was supported by the Swedish Medical Research Council (grant no. 8644), The European Union (BIOMED II grant BMH4-CT95-0527), the Swedish Society for Medical Research, the Stroke Foundation, the Bergendahls Foundation, the Fysiografiska Sallskapet in Lund, the Swedish Society of Medicine and the Wiberg Foundation. We thank Professor Anders Holtsberg at Lund University, for valuable help concerning the
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Proteomic analysis of the hippocampus in naïve and ischemic-preconditioned rat
2015, Journal of the Neurological SciencesTemporal and regional patterns of Smad activation in the rat hippocampus following global ischemia
2014, Journal of the Neurological SciencesCitation Excerpt :Previous studies have demonstrated that the activation of a number of molecules is altered in neurons prior to the onset of ischemia-induced neuronal cell death. These molecules include calpain, a Ca2 +-dependent protease [4–6], MAPK/ERK kinase 1, a tyrosine/threonine kinase [7], Akt, a serine/threonine kinase [8,9], and CREB, a transcriptional factor [6,10,11]. Such findings suggest that ischemia disturbs the homeostasis in affected neurons.