Yoshino A, Hovda D A, Katayama Y, Kawamata T, Becker D P
Division of Neurosurgery, UCLA School of Medicine 90024-6901.
J Cereb Blood Flow Metab. 1992 Nov;12(6):996-1006. doi: 10.1038/jcbfm.1992.137.
Immediately following fluid-percussion (F-P) brain injury, the hippocampus exhibits a marked increase in its local CMRglc (LCMRglc; mumol/100 g/min) as determined using [14C]2-deoxy-D-glucose autoradiography. This injury-induced increase in metabolism is followed in 6 h by a subsequent decrease in LCMRglc. These two postinjury metabolic states may be the result of ionic disruptions following trauma via stimulation of glutamate-gated ion channels. To determine if endogenous glutamate innervation to the CA1 region of the hippocampus can provide an anatomical basis for this proposed mechanism, it was removed by kainic-acid-induced destruction of CA3, and the effect on CA1 metabolism following concussive injury was studied. Five days before a lateral F-P injury (3.5-4.5 atm), kainic acid (0.5 microgram) or vehicle was stereotaxically injected into the left ventricle of 65 rats. Histological inspection indicated that kainic acid produced severe cell loss primarily in the CA3 region of the hippocampus ipsilateral to the injection. The metabolic results indicated that immediately following injury, animals with an intact hippocampus exhibited an increase in LCMRglc to 84.6 +/- 5 within the CA1 region, representing a 81.5% increase over controls. However, in the CA3-lesioned animals, CA1 showed no evidence of an injury-induced hypermetabolism, with LCMRglc remaining at control levels (51.4 +/- 3.9). At 6 h postinjury, the intact hippocampus exhibited a reduction of LCMRglc to rates of 40.7 +/- 4.7 within the CA1 region, representing a 17.9% reduction compared with controls. In contrast, CA3-lesioned animals exhibited less of an injury-induced decrease in LCMRglc within the CA1 region, exhibiting a mean rate of 43.4 +/- 4.5, representing only a 12.5% reduction compared with controls. These results indicate that the removal of the CA3 projection to CA1 protects the CA1 cells from the metabolic dysfunction typically seen following injury. This supports our previous work indicating the important role glutamate plays in the ionic flux and subsequent metabolic changes that follow traumatic brain injury.
在液体冲击（F-P）脑损伤后即刻，海马体通过[14C]2-脱氧-D-葡萄糖放射自显影测定显示其局部葡萄糖代谢率（LCMRglc；微摩尔/100克/分钟）显著增加。损伤诱导的这种代谢增加在6小时后会伴随着LCMRglc的随后下降。这两种损伤后的代谢状态可能是创伤后通过刺激谷氨酸门控离子通道导致离子紊乱的结果。为了确定海马体CA1区的内源性谷氨酸神经支配是否能为这一提出的机制提供解剖学基础，通过 kainic 酸诱导破坏CA3区将其去除，并研究了震荡性损伤后对CA1代谢的影响。在进行侧方F-P损伤（3.5 - 4.5个大气压）前5天，将 kainic 酸（0.5微克）或赋形剂立体定向注射到65只大鼠的左脑室内。组织学检查表明，kainic 酸主要导致注射侧海马体CA3区严重的细胞丢失。代谢结果表明，损伤后即刻，海马体完整的动物CA1区内LCMRglc增加至84.6±5，比对照组增加了81.5%。然而，在CA3损伤的动物中，CA1区没有显示出损伤诱导的代谢亢进的证据，LCMRglc保持在对照水平（51.4±3.9）。损伤后6小时，完整海马体的CA1区内LCMRglc降至40.7±4.7的水平，与对照组相比降低了17.9%。相比之下，CA3损伤的动物在CA1区内损伤诱导的LCMRglc下降较少，平均速率为43.4±4.5，与对照组相比仅降低了12.5%。这些结果表明，去除CA3到CA1的投射可保护CA1细胞免受损伤后通常出现的代谢功能障碍。这支持了我们之前的工作，表明谷氨酸在创伤性脑损伤后的离子通量及随后的代谢变化中起重要作用。
