RESUMEN
Epidemiological studies show positive relationship between mild-to-moderate hyperhomocysteinemia (hHcy) and the risk of cerebrovascular diseases. The study determines whether hyperhomocysteinemia (risk factor of brain ischemia) alone or in combination with the ischemic preconditioning (IPC) affects the ischemia-induced neurodegenerative changes and imbalance in MAPK/p-ERK1/2 and MAPK/p-p38 expression in the rat brains. hHcy was induced by subcutaneous administration of homocysteine (0.45 µmol/g body weight) twice a day at 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia and 2 days later, 15 min of global forebrain ischemia was induced by four vessel occlusion. We observed that hHcy alone significantly increased neurodegeneration by Fluoro-Jade C and TUNEL possitive cells in hippocampus as well as in cortex. We found elevated level of MAPK/p-ERK and decreased level of MAPK/p-p38 after pre-ischemic challenge by Western blot and fluorescent immunohistochemistry. In conclusion, preconditioning even if combined with hHcy could preserve the neuronal tissue from lethal ischemic effect. This study provides evidence for the interplay and tight integration between ERK and p38 MAPKs signalling mechanisms in response to the hHcy and also if in association with brain ischemia/IPC challenge in the rat brain.
Asunto(s)
Isquemia Encefálica/metabolismo , Hiperhomocisteinemia/metabolismo , Precondicionamiento Isquémico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Animales , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Homocisteína/sangre , Masculino , Ratas WistarRESUMEN
Global brain ischemia-reperfusion causes delayed cell death in hippocampal CA1 (cornus ammonis 1) pyramidal neurons after reperfusion. Ischemic tolerance evoked by preconditioning (IPC) represents a phenomenon of CNS adaptation to any subsequent ischemia. This paper was designed to describe changes in the mitogen-activated protein kinases (MAPK) protein pathways of the hippocampal area following by IPC. Ischemia was induced by a 4-vessels occlusion (4VO) and the rats were preconditioned by a non-injurious ischemia. Apoptotic markers were used to follow the degeneration process. Western blot and immunohistochemistry identified p-ERK (phosphorylated extracellular signal-regulated protein kinase) and p38 proteins in injured hippocampal areas. P-ERK quantification increased after IPC and reached the highest level at 24 hours after ischemia. Interestingly, neuroprotection induced by IPC lead to the opposite effect on MAPK/p38, where the level was lowest at 24 hours after ischemia. Taken together, the present study clearly demonstrates that p-ERK takes part in complex cascades triggered by IPC in the selectively vulnerable hippocampal region. In addition, paper describes a crosstalk between p-ERK and p-p38 which occurs after preconditioning maneuver in 4VO model of global ischemia.