Marklund Niklas, Salci Konstantin, Ronquist Gunnar, Hillered Lars
Department of Neuroscience, Neurosurgery, Uppsala University Hospital, SE-75185 Uppsala, Sweden.
Neurochem Res. 2006 Aug;31(8):1085-93. doi: 10.1007/s11064-006-9120-0. Epub 2006 Aug 15.
Impaired cerebral energy metabolism may be a major contributor to the secondary injury cascade that occurs following traumatic brain injury (TBI). To estimate the cortical energy metabolic state following mild and severe controlled cortical contusion (CCC) TBI in rats, ipsi-and contralateral cortical tissues were frozen in situ at 15 and 40 min post-injury and adenylate (ATP, ADP, AMP) levels were analyzed using high-performance liquid chromatography (HPLC) and the energy charge (EC) was calculated. At 15 min post-injury, mildly brain-injured animals showed a 43% decrease in cortical ATP levels and a 2.4-fold increase in AMP levels (P < 0.05), and there was a significant reduction of the ipsilateral cortical EC when compared to sham-injured animals (P < 0.05). At 40 min post-injury, the ipsilateral adenylate levels and EC had recovered to the values observed in the sham-injury group. In the severe CCC group, there was a 51% decrease in ipsilateral cortical ATP levels and a 5.3-fold increase in AMP levels with a significant reduction of cortical EC at 15 min post-injury (P < 0.05). At 40 min post-injury, a 2.6-fold ipsilateral increase in AMP levels and an 11% and 44% decrease in EC and ATP levels, respectively, remained (P < 0.05). A 37-38% reduction of the total adenylate pool was observed ipsilaterally in both CCC severity groups at the early time-point, and a 19% and 28% decrease remained in the mild and severe CCC groups, respectively, at 40 min post-injury. Significant contralateral ATP and EC changes were only observed in the severe CCC group at 40 min post-injury (P < 0.05). The energy-requiring secondary injury cascades that occur early post-injury do not challenge the brain tissue to the extent of ATP depletion and may provide a window of opportunity for therapeutic intervention.
脑能量代谢受损可能是创伤性脑损伤（TBI）后发生的继发性损伤级联反应的主要促成因素。为了评估大鼠轻度和重度控制性皮质挫伤（CCC）性TBI后的皮质能量代谢状态，在损伤后15分钟和40分钟将同侧和对侧皮质组织原位冷冻，并使用高效液相色谱（HPLC）分析腺苷酸（ATP、ADP、AMP）水平，并计算能量电荷（EC）。损伤后15分钟，轻度脑损伤动物的皮质ATP水平降低43%，AMP水平升高2.4倍（P<0.05），与假损伤动物相比，同侧皮质EC显著降低（P<0.05）。损伤后40分钟，同侧腺苷酸水平和EC已恢复到假损伤组观察到的值。在重度CCC组中，损伤后15分钟同侧皮质ATP水平降低51%，AMP水平升高5.3倍，皮质EC显著降低（P<0.05）。损伤后40分钟，同侧AMP水平升高2.6倍，EC和ATP水平分别降低11%和44%（P<0.05）。在两个CCC严重程度组的早期时间点，同侧总腺苷酸池均减少37-38%，在损伤后40分钟，轻度和重度CCC组分别仍有19%和28%的下降。仅在重度CCC组损伤后40分钟观察到对侧ATP和EC有显著变化（P<0.05）。损伤后早期发生的需要能量的继发性损伤级联反应对脑组织的挑战程度未达到ATP耗竭的程度，可能为治疗干预提供一个机会窗口。
