Selective sparing of hippocampal CA3 cells following in vitro ischemia is due to selective inhibition by acidosis
| العنوان: | Selective sparing of hippocampal CA3 cells following in vitro ischemia is due to selective inhibition by acidosis |
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| المؤلفون: | Kimmo Jensen, Tobias Cronberg, Anna Rytter, Tadeusz Wieloch |
| المصدر: | European Journal of Neuroscience. 22:310-316 |
| بيانات النشر: | Wiley, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | medicine.medical_specialty, musculoskeletal, neural, and ocular physiology, General Neuroscience, Ischemia, Hippocampal formation, Biology, medicine.disease, Brain ischemia, Endocrinology, nervous system, Internal medicine, Extracellular fluid, medicine, Excitatory postsynaptic potential, Extracellular, NMDA receptor, medicine.symptom, Neuroscience, Acidosis |
| الوصف: | A brief global ischemic insult to the brain leads to a selective degeneration of the pyramidal neurons in the hippocampal CA1 region while the neurons in the neighbouring CA3 region are spared. The reason for this difference is not known. The selective vulnerability of CA1 neurons to ischemia can be reproduced in vitro in murine organotypic slice cultures, if the ion concentrations in the medium during the anoxic/aglycemic insult are similar to that in the brain extracellular fluid during ischemia in vivo. As acidosis develops during ischemia, we studied the importance of extracellular pH for selective vulnerability. We found that cell death in the CA1 and CA3 regions was equally prevented by removal of calcium from the medium or following blockade of the N-methyl-D-aspartate (NMDA) receptor by D-2 amino-5-phosphonopentanoic-acid (D-APV). On the other hand, damage to the CA3 neurons markedly decreased with decreasing pH following in vitro ischemia, while the degeneration of CA1 neurons was less pH dependent. Patch-clamp recordings from pyramidal neurons in the CA1 and CA3 regions, respectively, revealed a pronounced inhibition of NMDA-receptor mediated excitatory postsynaptic currents (EPSCs) at pH 6.5 that was equally pronounced in the two regions. However, when changing pH from 6.5 to 7.4 the recovery of the EPSCs was significantly slower in the CA3 region. We conclude that acidosis selectively protects CA3 pyramidal neurons during in vitro ischemia, and differentially affects the kinetics of NMDA receptor activation, which may explain the difference in vulnerability between CA1 and CA3 pyramidal neurons to an ischemic insult. |
| تدمد: | 1460-9568 0953-816X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d1d047784a660a58f120aec9148009f3 https://doi.org/10.1111/j.1460-9568.2005.04235.x |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........d1d047784a660a58f120aec9148009f3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14609568 0953816X |
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