Severe Human Head Injury Research Articles

O-15-219 - Glutamate, lactate and glucose — Ischemic thresholds determined according to cerebral blood flow measurements in severe human head injury

O-15-219 - Glutamate, lactate and glucose — Ischemic thresholds determined according to cerebral blood flow measurements in severe human head injury

Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study.

Experimental traumatic brain injury studies have shown that cerebral hyperglycolysis is a pathophysiological response to injury-induced ionic and neurochemical cascades. This finding has important implications regarding cellular viability, vulnerability to secondary insults, and the functional capability of affected regions. Prior to this study, posttraumatic hyperglycolysis had not been detected in humans. The characteristics and incidence of cerebral hyperglycolysis were determined in 28 severely head injured patients using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). The local cerebral metabolic rate of glucose (CMRG) was calculated using a standard compartmental model. In six of the 28 patients, the global cerebral metabolic rate of oxygen (CMRO2) was determined by the simultaneous measurements of arteriovenous differences of oxygen and cerebral blood flow (xenon-133). Hyperglycolysis, defined as an increase in glucose utilization that measures two standard deviations above expected levels, was documented in all six patients in whom both FDG-PET and CMRO2 determinations were made within 8 days of injury. Five additional patients were found to have localized areas of hyperglycolysis adjacent to focal mass lesions. Within the 1st week following the injury, 56% of patients studied had presumptive evidence of hyperglycolysis. The results of this study indicate that the metabolic state of the traumatically injured brain should be defined differentially in terms of glucose and oxygen metabolism. The use of FDG-PET demonstrates that hyperglycolysis occurs both regionally and globally following severe head injury in humans. The results of this clinical study directly complement those previously reported in experimental brain-injury studies, indicating the capability of imaging a fundamental component of cellular pathophysiology characteristic of head injury.

Rely

Rely

Glutamate release and cerebral blood flow after severe human head injury.

Elevations of extracellular glutamate have been found in patients with prolonged brain ischemia and focal cerebral contusions, following severe head injury. About 30% of severely head injured patients develop cerebral ischemia, defined as CBF < 18 ml/100g/min. Patients with both global and regional cerebral ischemia have the worst outcome. However, the relationship between CBF and EAA release is not well understood in head injured humans, and may differ from the findings in normal animals. To study the relationship between EAA release and CBF after severe head injury, we performed cerebral blood flow measurements using stable xenon enhanced computed tomography and correlated these with glutamate release in the extracellular fluid, measured by continuous microdialysis, in 25 severely head injured patients. Sustained cerebral blood flow reductions below the threshold for ischemic neuronal damage was closely related to massive excitatory amino acid release, as in previous animal studies. In patients without secondary ischemia, or focal contusions, delayed post-traumatic glutamate release appeared to be only transient or did not occur at all.

Selective Loss of Neurons From the Thalamic Reticular Nucleus Following Severe Human Head Injury

The GABAergic neurons of the thalamic reticular nucleus, or nucleus reticularis thalami (RT), have been implicated as important components in attentional processing systems. Neurons in the RT are exquisitely sensitive to degeneration following kainic and domoic acid toxicity, experimental global ischemia, human cardiac arrest, and experimental closed head injury in nonhuman primates. The present study was performed to establish whether the selective loss of human RT neurons occurred following severe head injury. Brains from 37 human nonsurvivors of head injury were examined for evidence of RT neuronal loss. RT lesions in were found in 36 of 37 cases, representing 65 of 73 (89%) of the reticular nuclei examined. The incidence of RT lesions was similar in all age groups: 13 of 14 cases (92.9%) in the pediatric (< or = 16 years) group, 33 of 37 (89.2%) in the young adult (18-45 years) group, and 19 of 22 (86.4%) in the older adult (> 45 years) group. RT lesions were characterized by loss of one fourth to three fourths of the neurons from the region of the nucleus associated with the frontal cortex and thalamic mediodorsal (MD) and ventrolateral (VL) nuclei. Sparing of RT neurons correlated highly with the presence of extensive frontal cortical lesions, suggesting that an intact corticothalamic projection was necessary for RT degeneration following head injury. A pathologic cascade with a prominent excitotoxic component is proposed. The loss of these inhibitory thalamic reticular neurons and the resultant thalamic and neocortical neuronal dysfunctions may underlie some forms of attentional deficits that persist following head injury.

Diffuse axonal injury and traumatic coma in the primate.

Traumatic coma was produced in 45 monkeys by accelerating the head without impact in one of three directions. The duration of coma, degree of neurological impairment, and amount of diffuse axonal injury (DAI) in the brain were directly related to the amount of coronal head motion used. Coma of less than 15 minutes (concussion) occurred in 11 of 13 animals subjected to sagittal head motion, in 2 of 6 animals with oblique head motion, and in 2 of 26 animals with full lateral head motion. All 15 concussioned animals had good recovery, and none had DAI. Conversely, coma lasting more than 6 hours occurred in one of the sagittal or oblique injury groups but was present in 20 of the laterally injured animals, all of which were severely disabled afterward. All laterally injured animals had a degree of DAI similar to that found in severe human head injury. Coma lasting 16 minutes to 6 hours occurred in 2 of 13 of the sagittal group, 4 of 6 in the oblique group, and 4 of 26 in the lateral group, these animals had less neurological disability and less DAI than when coma lasted longer than 6 hours. These experimental findings duplicate the spectrum of traumatic coma seen in human beings and include axonal damage identical to that seen in sever head injury in humans. Since the amount of DAI was directly proportional to the severity of injury (duration of coma and quality of outcome), we conclude that axonal damage produced by coronal head acceleration is a major cause of prolonged traumatic coma and its sequelae.