Postconcussion syndrome (PCS) refers to symptoms and signs commonly occurring after mild head injury. The pathogenesis of PCS is unknown. The authors quantitatively analyzed EEG recordings, localized brain sources for abnormal activity, and correlated it with imaging studies. Data from 17 patients with neurologic symptomatology consistent with ICD-10 criteria for PCS was analyzed. Normalized quantitative EEG (QEEG) revealed significantly higher power in the delta band and lower power in the alpha band compared with matched controls. The generators for the abnormal rhythms were focally localized in neocortical regions. Brain computerized tomography and/or MRI did not reveal focal abnormality at the time of diagnosis. Single photon emission computed tomography (SPECT) after 99mTc-ethylcysteinate dimer administration showed a focal reduction in perfusion in 85% (n = 11) of the patients, and abnormal blood-brain barrier (BBB) after 99mTc-diethylenetriaminepentaacetic acid administration in 73% (n = 8). In 75% of these patients, low-resolution brain electromagnetic tomography analysis showed that the generators for abnormal rhythms were closely related to the anatomic location of the BBB lesion. These data point to focal cortical dysfunction in conjunction with BBB disruption and hypoperfusion as a possible mechanism of pathogenesis in at least some PCS patients, and offer QEEG and SPECT as important tools in evaluating these patients.

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In previous studies, we have shown that by increasing the brain-to-blood glutamate efflux upon scavenging blood glutamate with either oxaloacetate or pyruvate, one achieves highly significant neuroprotection particularly in the context of traumatic brain injury. The current study examines, for the first time, how the blood glutamate scavenging properties of glutamate-pyruvate transaminase (GPT), alone or in combination with pyruvate, may contribute to the spectrum of its neuroprotective mechanisms and improve the outcome of rats exposed to brain ischemia, as they do after head trauma. Rats that were exposed to permanent middle cerebral artery occlusion (MCAO) and treated with intravenous 250 mg/kg pyruvate had a smaller volume of infarction and reduced brain edema, resulting in an improved neurological outcome and reduced mortality compared to control rats treated with saline. Intravenous pyruvate at the low dose of 31.3 mg/kg did not demonstrate any neuroprotection. However, when combined with 0.6 mg/kg of GPT there was a similar neuroprotection observed as seen with pyruvate at 250 mg/kg. Animals treated with 1.69 g/kg glutamate had a worse neurological outcome and a larger extent of brain edema. The decrease in mortality, infarcted brain volume and edema, as well as the improved neurological outcome following MCAO, was correlated with a decrease in blood glutamate levels. We therefore suggest that the blood glutamate scavenging activity of GPT and pyruvate contributes to the spectrum of their neuroprotective mechanisms and may serve as a new neuroprotective strategy for the treatment of ischemic stroke.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and early predictors of neurological outcomes are of great clinical importance. Cell free DNA (CFD), a biomarker used for the diagnosis and monitoring of several diseases, has been implicated as a possible prognostic indicator after TBI. The purpose of this study was to determine the pattern and timing of CFD levels after TBI, and whether a relationship exists between the level of CFD and brain edema and neurological outcomes. Thirty-nine Sprague-Dawley rats were randomly assigned to two groups: rats in group 1 (sham group) were anesthetized and had a scalp incision without TBI, and rats in group 2 were anesthetized and had a scalp incision with TBI, which was induced by using a weight drop model that causes diffuse brain injury. A neurological severity score (NSS) was assessed at 1, 24, and 48 h after TBI. CFD was measured via blood samples drawn at t=0 (baseline), 12, 24, 48, 72, and 120 h after TBI. At 48 h after TBI, brain edema was determined in a subgroup of 11 rats by calculating the difference between rats' wet and dry brain weight. The significance of comparisons between and within groups (CFD levels, brain water content, and NSS) were determined using the Kruskal-Wallis, Mann-Whitney and Student t test. The correlation between CFD levels and the NSS, as well as between CFD levels and the extent of brain edema, was calculated using the Spearman and Pearson tests, respectively. Compared with baseline levels, the CFD levels in rats subjected to TBI were significantly increased at 24 and 48 h after TBI (p<0.01 and p<0.05, respectively). A positive correlation was demonstrated between CFD levels 24 h following TBI and the extent of brain edema (r=0.63, p<0.05), as well as between CFD levels and the NSS (r=0.79, p<0.005). In this study, we demonstrated an increase in CFD levels after TBI, as well as a correlation between CFD levels and brain edema and NSS. CFD levels may provide a quick, reliable, and simple prognostic indicator of neurological outcome in animals after TBI. Its role in humans has not been clearly elucidated, but has potentially significant clinical implications.