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Excitatory Amino Acids in Cerebrospinal Fluid of Patients with Acute Head Injuries

¹ Chromatographic Center, Lanzhou Institute of Chemical Physics Chinese Academy of Sciences, 342 Tianshui Rd., Lanzhou, China 730000.
² Department of Neurosurgery, The Second Affiliated Hospital of Lanzhou Medical College, 80 Cuiyingmen, Lanzhou, China 730030.
³ Department of Neurosurgery, The First Affiliated Hospital of Lanzhou Medical College, 1 Donggang West Rd., Lanzhou, China 730000.

^aAuthor for correspondence. E-mail lzwzh{at}public.lz.gs.cn

Background: The excitatory amino acids (EAAs) glutamate (Glu) and aspartate (Asp) play a role in the pathogenesis of postischemic and posttraumatic brain insult. The changes of EAAs in cerebrospinal fluid (CSF) of patients with traumatic brain injury are incompletely understood.

Methods: We used reversed-phase HPLC with precolumn derivatization with o-phthalaldehyde and fluorescence detection to measure Glu and Asp in CSF of 42 patients with acute head injury and 9 control adults without neurologic diseases. We assessed the Glasgow Coma Scale (GCS) on admission, the main lesion patterns on computed tomography (CT) scan within 24 h post trauma, and the Glasgow Outcome Scale (GOS) 3 months post injury.

Results: The mean concentrations of Glu and Asp in CSF in the brain-injured group were significantly higher than those of the control group (Glu, P <0.001; Asp, P <0.05). In patients admitted within 24 h after severe injury (n = 13), peak Glu values appeared within 48 h in 11 patients (85%), and the mean value remained higher than control values at day 7 (P <0.02). The concentrations of EAAs were higher in patients with severe injuries (GCS 8) than in those with milder injuries (Glu, P <0.001; Asp, P <0.05). GCS and peak EAAs correlated negatively (Glu, r_s = -0.5706, P <0.001; Asp, r_s = -0.5503, P <0.001). The patients with focal brain contusion on initial CT scan (n = 8) had a significantly lower peak Glu value than the patients with other patterns (n = 8–15; P <0.02 to 0.001). The peak value of EAAs in the poor-outcome group (including severe disability, vegetative state, and death) was significantly higher than in the good-outcome group (good recovery and moderate disability; Glu, P <0.001; Asp, P <0.01); GOS was closely correlated to the EAA values (Glu, r_s = 0.5737, P <0.001; Asp, r_s = 0.5470, P <0.001).

Conclusions: The EAA concentrations in CSF increase after acute head injury and remain higher for at least 1 week post injury in severely injured patients. The more severe the trauma, the more obvious the excitotoxicity induced by EAAs and the worse the outcome.

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				R. Sethuraman, T. L. Lee, and S. Tachibana Simple Quantitative HPLC Method for Measuring Physiologic Amino Acids in Cerebrospinal Fluid without Pretreatment Clin. Chem., March 1, 2004; 50(3): 665 - 669. [Full Text] [PDF]

				G. Franz, R. Beer, A. Kampfl, K. Engelhardt, E. Schmutzhard, H. Ulmer, and F. Deisenhammer Amyloid beta 1-42 and tau in cerebrospinal fluid after severe traumatic brain injury Neurology, May 13, 2003; 60(9): 1457 - 1461. [Abstract] [Full Text] [PDF]