Neuroprotection of creatine supplementation in neonatal rats with transient cerebral hypoxia-ischemia
Neuroprotection of creatine supplementation in neonatal rats with transient cerebral hypoxia-ischemia
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DOI：
10.1159/000069043
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发表时间：
2002-09-01
影响因子：
2.9
通讯作者：
Wagner, BP
中科院分区：
文献类型：
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作者：
Adcock, KH;Nedelcu, J;Wagner, BP
我们假设补充肌酸（Cr）可以保护能量代谢，从而改善新生大鼠模型中严重但短暂的脑缺氧缺血（HI）后的能量衰竭和脑水肿程度。6日龄（P6）大鼠连续3天皮下注射一水铬（3 g/kg体重/天），然后在P9时进行P-31-磁共振波谱（MRS）检查。在第二组中，P4大鼠接受相同的铬剂量为3天，然后单侧颈总动脉结扎1小时后，100分钟的缺氧（8%O-2）在P7。将大鼠的直肠温度保持在37 ℃，直到HI后24小时进行磁共振成像。补铬3天显著提高了能量潜力，即磷酸肌酸与β-核苷酸三磷酸的比率通过P-31-MRS测量的PCr/β-NTP（PCr/β-NTP）和PCr/无机磷酸盐（PCr/Pi）。与对照组相比，接受Cr的半球脑缺氧缺血损伤的大鼠显示出水肿脑组织体积的显著减少（25%），如通过扩散-加权成像（DWI）。因此，预防性补充铬表现出显着的神经保护作用后24小时短暂脑HI。我们假设，神经保护可能是由于一个更大的代谢底物池的可用性，导致减少二次能量衰竭，因为DWI已被报道与PCr/Pi比值在急性期的损伤。铬的额外保护作用可能与防止钙超载、防止线粒体通透性转换孔开放和直接抗氧化作用有关。版权所有（C）2002 S. Karger AG，巴塞尔。
We hypothesized that creatine (Cr) supplementation would preserve energy metabolism and thus ameliorate the energy failure and the extent of brain edema seen after severe but transient cerebral hypoxia-ischemia (HI) in the neonatal rat model. Six-day-old (P6) rats received subcutaneous Cr monohydrate injections for 3 consecutive days (3 g/kg body weight/day), followed by P-31-magnetic resonance spectroscopy (MRS) at P9. In a second group, P4 rats received the same Cr dose as above for 3 days prior to unilateral common carotid artery ligation followed 1 h later by 100 min of hypoxia (8% O-2) at P7. Rats were maintained at 37 C rectal temperature until magnetic resonance imaging was performed 24 h after HI. Cr supplementation for 3 days significantly increased the energy potential, i.e. the ratio of phosphocreatine to beta-nucleotide triphosphate (PCr/betaNTP) and PCr/inorganic phosphate (PCr/Pi) as measured by P-31-MRS. Rats with hemispheric cerebral hypoxic-ischemic insult that had received Cr showed a significant reduction (25%) of the volume of edemic brain tissue compared with controls as calculated from diffusion-weighted images (DWI). Thus, prophylactic Cr supplementation demonstrated a significant neuroprotective effect 24 h after transient cerebral HI. We hypothesize that neuroprotection is probably due to the availability of a larger metabolic substrate pool leading to a reduction of the secondary energy failure because DWI has been reported to correlate with the PCr/Pi ratio in the acute phase of injury. Additional protection by Cr may be related to prevention of calcium overload, prevention of mitochondrial permeability transition pore opening and direct antioxidant effects. Copyright (C) 2002 S. Karger AG, Basel.