A 6-item Orientation-Memory-Concentration Test has been validated as a measure of cognitive impairment. This test predicted the scores on a validated 26-item mental status questionnaire of two patient groups in a skilled nursing home, patients in a health-related facility, and in a senior citizens' center. There was a positive correlation between scores on the 6-item test and plaque counts obtained from the cerebral cortex of 38 subjects at autopsy. This test, which is easily administered by a nonphysician, has been shown to discriminate among mild, moderate, and severe cognitive deficits.

Image analysis apparatus was used to count and measure glial and neuronal perikarya in ten size classes in the midfrontal region and superior temporal gyrus of 18 patients with senile dementia of the Alzheimer type for comparison with 12 age-matched normal specimens. Brain weight was about 8% less in the dementia group. The major differences had to do with larger neurons, which in dementia were reduced by about 40% in the frontal cortex and 46% in the temporal region. The concentration of neuritic plaques did not correlate significantly with brain weight, cortical thickness, or cell counts.

In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory neurons with cell bodies in dorsal root or trigeminal ganglia produce glutaminase, the synthetic enzyme for glutamate, and transport the enzyme in mitochondria to peripheral terminals. Vesicular glutamate transporters fill neurotransmitter vesicles with glutamate and they are shipped to peripheral terminals. Intense noxious stimuli or tissue damage causes glutamate to be released from peripheral afferent nerve terminals and augmented release occurs during acute and chronic inflammation. The site of action for glutamate can be at the autologous or nearby nerve terminals. Peripheral nerve terminals contain both ionotropic and metabotropic excitatory amino acid receptors (EAARs) and activation of these receptors can lower the activation threshold and increase the excitability of primary afferents. Antagonism of EAARs can reduce excitability of activated afferents and produce antinociception in many animal models of acute and chronic pain. Glutamate injected into human skin and muscle causes acute pain. Trauma in humans, such as arthritis, myalgia, and tendonitis, elevates glutamate levels in affected tissues. There is evidence that EAAR antagonism at peripheral sites can provide relief in some chronic pain sufferers.

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Most, if not all, dorsal root ganglion (DRG) neurons use the neurotransmitter glutamate. There are, however, conflicting reports of the percentages of DRG neurons that express glutaminase (GLS), the enzyme that synthesizes glutamate, ranging from 30% to 100% of DRG neurons. Defining DRG neuron populations by the expression of proteins like GLS, which indicates function, is routinely accomplished with immunolabeling techniques. Proper characterization of DRG neuron populations relies on accurate detection of such antigens. It is known intuitively that fixation can alter immunoreactivity (IR). In this study, we compared the effects of five formaldehyde concentrations between 0.25% and 4.0% (w/v) and five picric acid concentrations between 0.0% and 0.8% (w/v) on the IR of GLS, the voltage-gated sodium channel 1.8 (Nav 1.8), and the capsaicin receptor TRPV1. We also compared the effects of five incubation time lengths from 2 to 192 hr, in primary anti-serum on IR. Lowering formaldehyde concentration elevated IR for all three antigens, while raising picric acid concentration increased Nav 1.8 and TRPV1 IR. Increasing IR improved detection sensitivity, which led to higher percentages of labeled DRG neurons. By selecting fixation conditions that optimized IR, we found that all DRG neurons express GLS, 69% of neurons express Nav 1.8, and 77% of neurons express TRPV1, indicating that some previous studies may have underestimated the percentages of DRG neurons expressing these proteins. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.