Modulation of receptive field properties of thalamic somatosensory neurons by the depth of anesthesia. The dominant frequency of electrocorticographic (ECoG) recordings was used to determine the depth of halothane or urethan anesthesia while recording extracellular single-unit responses from thalamic ventral posterior medial (VPM) neurons. A piezoelectric stimulator was used to deflect individual whiskers to assess the peak onset latency, magnitude, probability of response, and receptive field (RF) size. There was a predictable increase in the dominant ECoG frequency from deep stage IV to light stage III-1 anesthetic levels. There was no detectable frequency at stage IV, a 1- to 2-Hz dominant frequency at stage III-4, 3-4 Hz at stage III-3, 5-7 Hz at stage III-2, and a dual 6- and 10- to 13-Hz pattern at stage III-1. Reflexes and other physical signs showed a correlation with depth of anesthesia but exhibited too much overlap between stages to be used as a criterion for any single stage. RF size and peak onset latency of VPM neurons to whisker stimulations increased between stage III-4 and III-1. A dramatic increase in RF size and response latency occurred at the transition from stage III-3 (RF size approximately 2 whiskers, latency approximately 7 ms) to stage III-2 (RF size approximately 6 whiskers, latency approximately 11 ms). Response probability and magnitude decreased from stage III-4 to stage III-3 and III-2. No responses were ever evoked in VPM cells by vibrissa movement at stage IV. These changes in VPM responses as a function of anesthetic depth were seen only when the nucleus principalis (PrV) and nucleus interpolaris (SpVi) trigeminothalamic pathways were both intact. Eliminating SpVi inputs to VPM, either by cutting the primary trigeminal afferent fibers to SpVi or cutting axons projecting from SpVi to VPM, immediately reduced the RF size to fewer than three whiskers. In addition, the predictable changes in VPM response probability, response magnitude, and peak onset latency at different anesthetic depths were all absent after SpVi pathway interruption. We conclude that 1) the PrV input mediates the near "one-to-one" correspondence between a neuronal response in VPM and a single mystacial whisker, 2) in contrast, the SpVi input to VPM is primarily responsible for the RF properties of VPM neurons at light levels of anesthesia and presumably in the awake animal, and 3) alterations in VPM responses produced by changing the depth of anesthesia are due to its selective influence on the properties mediated by SpVi inputs at the level of the thalamus.

Patients with traumatic brain injury (TBI) routinely exhibit cerebral glucose uptake in excess of that expected by the low levels of oxygen consumption and lactate production. This brings into question the metabolic fate of glucose. Prior studies have shown increased flux through the pentose phosphate cycle (PPC) during cellular stress. This study assessed the PPC after TBI in humans.[1,2-13 C 2 ]glucose was infused for 60 mins in six consented, severe-TBI patients (GCS < 9) and six control subjects. Arterial and jugular bulb blood sampled during infusion was analyzed for 13 C-labeled isotopomers of lactate by gas chromatography/mass spectroscopy. The product of lactate concentration and fractional abundance of isotopomers was used to determine blood concentration of each isotopomer. The difference of jugular and arterial concentrations determined cerebral contribution. The formula PPC = (m1/m2)/(3 + (m1/m2)) was used to calculate PPC flux relative to glycolysis. There was enrichment of [1,2-13 C 2 ]glucose in arterial-venous blood (enrichment averaged 16.6% in TBI subjects and 28.2% in controls) and incorporation of 13 C-label into lactate, showing metabolism of labeled substrate. The PPC was increased in TBI patients relative to controls (19.6 versus 6.9%, respectively; P = 0.002) and was excellent for distinguishing the groups (AUC = 0.944, P < 0.0001). No correlations were found between PPC and other clinical parameters, although PPC was highest in patients studied within 48 h of injury (averaging 33% versus 13% in others; P = 0.0006). This elevation in the PPC in the acute period after severe TBI likely represents a shunting of substrate into alternative biochemical pathways that may be critical for preventing secondary injury and initiating recovery.

Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we studied the correlation between CMRglc and the level of consciousness within the first month following human traumatic brain injury. Forty-three FDG-PET scans obtained on 42 mild to severely head-injured patients were quantitatively analyzed for the determination of regional cerebral metabolic rate of glucose (CMRglc). Reduction of cerebral glucose utilization, defined as a CMRglc of < or =4.9 mg/100 g/min, was present regionally in 88% of the studies. The prevalence of global cortical CMRglc reduction was higher in severely head-injured patients (86% versus 67% mild-moderate), although the absolute magnitude was similar across the injury severity spectrum (mean CMRglc 3.9 +/- 0.6 mg/100 g/min). The level of consciousness, as measured by the Glasgow Coma Scale, correlated poorly with the global cortical CMRglc value (r = 0.08; p = 0.63). With regards to severity of head injury, this correlation was worst for the severely injured (r = -0.11; p = 0.58) and better for the mildly injured patients (r = 0.50; p = 0.07). In most cases, intraparenchymal hemorrhagic lesions were associated with either focal CMRglc reduction or elevation. It is concluded that the etiologies of CMRglc reduction are likely multifactorial given the complex nature of traumatic brain injury and that the reduction of CMRglc represents a fundamental pathobiologic state following head injury that is not tightly coupled to level of consciousness.

The metabolic fate of [1,2 13C]-labeled glucose was determined in male control and unilateral controlled cortical impact (CCI) injured rats at 3.5 and 24 h after surgery. The concentration of 13C-labeled glucose, lactate, glutamate and glutamine were measured in the injured and contralateral cortex. CCI animals showed a 145% increase in 13C lactate in the injured cortex at 3.5 h, but not at 24 h after injury, indicating increased glycolysis in neurons and/or astrocytes ipsilateral to CCI. Total levels of 13C glutamate in cortical tissue extracts did not differ between groups. However, 13C glutamine increased by 40% in the left and 98% in the right cortex at 3.5 h after injury, most likely resulting from an increase in astrocytic metabolism of glutamate. Levels of 13C incorporation into the glutamine isotopomers had returned to control levels by 24 h after CCI. The singlet to doublet ratio of the lactate C3 resonances was calculated to estimate the flux of glucose through the pentose phosphate pathway (PPP). CCI resulted in bilateral increases (9-12%) in the oxidation of glucose via the PPP, with the largest increase occurring at 24 h. Since an increase in PPP activity is associated with NADPH generation, the data suggest that there was an increasing need for reducing equivalents after CCI. Furthermore, 13C was incorporated into glutamate and glutamine isotopomers associated with multiple turns of the tricarboxylic acid (TCA) cycle, indicating that oxidative phosphorylation of glucose was maintained in the injured cortex at 3.5 and 24 h after a moderate to severe CCI injury.

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