Developmental assessment of spinal cord and cortical evoked potentials after tibial nerve stimulation: effects of age and stature on normative data during childhood.

Somesthetic information from lower extremities is processed by cerebral cortex after traversing the sensory pathways of peripheral nerve, spinal cord, brain-stem and thalamus. Clinical utility of somatosensory evoked potentials (SSEPs) during human development requires systematic analysis of normative data acquired during various stages of body growth and nervous system maturation. Accordingly, SSEPs after tibial nerve stimulation were studied in 32 normal awake children (1-8 years old) and compared with values obtained in young adults (18-40 years old). Potentials were recorded from the tibial nerve (N5), first lumbar spinous process (N14), seventh cervical spinous process (N20) and from the scalp, 2 cm behind the vertex (P28). In all children studied, the N5, N14 and N20 latencies were positively correlated with age and height yielding a predictive nomogram. An extremely variable electropositive cortical SSEP was recorded from Cz' which did not show a highly predictable linear relationship in association with a relatively poor correlation coefficient for height and age. It may be concluded that between 1 and 8 years of normal postnatal development, latencies reflecting peripheral nerve and lumbar spinal cord vary directly with height and age and can be represented by a simple cable model of a lengthening myelinated pathway. In contrast, the latency of the cortical SSEP reflects asynchronous maturation of elongating polysynaptic pathways and apparently requires a more complex model for prediction in order to enhance its clinical utility.

Strain differences and laminar localization of structural neurochemical changes in aging rat.

To obtain comparisons of age-related microchemical changes in cerebral cortex of two commonly employed rat strains (Fischer 344 and Sprague-Dawley), neurochemical assays of substances regarded as quantitative indices of structural entities in brain were performed. These included DNA as a marker for cells, lipid sialoganglioside as an index of neuronal membrane mass, and galactocerebroside as an index of myelin. Fischer 344 rats were studied at 3-4 months (young), 14-16 months (middle age) and 25-28 months (old). Sprague-Dawleys were examined at 3-6 months (young), 14-17 months (middle age) and 25-28 months (old). Significant differences in the time courses of changes occurred; Fischer rats increased their brain weight at each aging point, while Sprague-Dawley rats reached stable brain weights by 4 months of age. Neither strain had a significant change in cell packing density of somatosensory cortex as measured by DNA. However, total ganglioside sialic acid declined in both strains, occurring by middle age in the Fischer and not until senescence in the Sprague-Dawley cortex. Cerebroside galactose increased in the Fischer between young and middle age, and was not further elevated in the older group. The Sprague-Dawley had its major increase in this marker between the middle aged and senescent groups. Intralaminar assays of these same markers in young and old Fisher 344 rats again indicated that DNA did not change, and that sialoganglioside was lost from all layers of the cortex in equal amounts. However, the increase in galactocerebroside resulted entirely from increases in the lower lamina of somatosensory cortex (lamina IV and below), suggesting on-going myelination of afferent and efferent axons. The time course of lipid membrane alteration is strain-dependent and selective as to cortical laminar localization. The findings are discussed in reference to human aging change in the same neurochemical indices.

Autoradiographic localization of 3H-digoxin binding by neural cells in the medulla.

The purpose of this investigation was to localize binding sites for the cardiac glycoside digoxin in the medulla of the rat in vivo. Adult male Sprague-Dawley rats were injected (IV) with 3H-digoxin and killed 30 minutes later. Autoradiographs of medullas showed evidence of 3H-digoxin binding to small- and medium-sized neural cells in the regions of the nucleus solitarius, dorsal motor nucleus of the vagus, area postrema, and in the zone between the area postrema and the underlying neuropil. However, the parasympathetic preganglionic neurons of the dorsal motor nucleus were not labeled. The 3H-digoxin-labeled cells in the medulla were located mainly in the commissural and medial portions of nucleus solitarius at the level of the area postrema. Animals injected with unlabeled digoxin followed by 3H-digoxin showed reduced binding of radioactivity. The small- and medium-sized neurons of the caudal portions of the nucleus solitarius are internuncial in position with respect to cardiovascular afferents of the glossopharyngeal and vagus nerves and sympathetic and parasympathetic cardiovascular efferent neurons of the medulla. The results of this study suggest that these 3H-digoxin-labeled cells, presumably neurons of nucleus solitarius, may possess high affinity binding sites for digoxin. Further, the area postrema, which lacks a blood-brain barrier, may provide a portal of entry for 3H-digoxin into regions of the medulla known to contain neurons that play a role in the regulation of cardiac rhythm.

Lumbar spinal cord and early cortical evoked potentials after tibial nerve stimulation: effects of stature on normative data.

Short-latency somatosensory evoked responses to tibial nerve stimulation were recorded simultaneously over the spinous processes of the lumbar vertebrae and scalp in normal young subjects. This non-invasive test revealed values which are highly reproducible and could be closely correlated with subject-related variables such as height and leg length. A nomogram describing the close relationship between absolute latency of various response components and stature was derived and shown to be an important variable in the establishment of normative data nad interpretation of SSEP in relation to disorders affecting the peripheral and central nervous system. In contrast, central conduction times of interpeak intervals (N22-P37 and N22-N45) were unrelated to variations in the subjects, stature providing a reliable clinical measure in the assessment of the central somatosensory pathway.

Aging, senile dementia, and the intralaminar microchemistry of cerebral cortex.

We compared the microchemical architecture or right frontal isocortex from patients with senile dementia and age-matched and younger controls. Neuronal connectivity within deep lamina of the cortical column (Brodmann area 9) tended to decline in normal aging and was profoundly depleted in senile dementia. In both aging and senile dementia, there was a significant 20% loss of total cells (neurons and glia) in cortical layers III to VI. In senile dementia, marked diminution of total ganglioside sialic acid per neuron and galactocerebroside per cell in the lower lamina far exceeded alterations associated with aging itself. This structural loss may imply deafferentation of the cortex, owing to loss of projections from subcortical areas such as nucleus basalis. Selective vulnerability of axodendritic arborization of neurons in lower lamina may be correlated to the impaired cognitive functions of senile dementia.

Abnormal maturation of cerebral cortex and behavioral deficit in adult rats after neonatal administration of antibodies to ganglioside.

Five-day-old rats received a single injection (50 microliter) of antiserum to ganglioside into the cisterna magna and were compared to control animals injected with the antiserum which had been absorbed with pure GM1 ganglioside to remove the specific antibodies. Both groups showed normal rates of body growth. However, animals receiving antiganglioside serum had, at 60 days of age, impaired performance when tested on a complex learning task (DRL) as well as chemical and morphological alterations in the somatosensory cerebral cortex. Gross morphology and wet weight of whole brain were normal in both groups. Microchemical analysis of somatosensory isocortex revealed a normal content of total solids, protein, and DNA. However, ganglioside sialic acid, galactocerebroside, and RNA were decreased by 31%, 32% and 25% of control values, respectively (P less than 0.01). Quantitative measurements of oblique dendrites of Golgi-stained cortical pyramidal neurons revealed a 31% decrease in the number of spines. Additionally, the majority of spines were of the stubby configuration, whereas dendrites from controls were populated predominately by thin spines. These observations suggest that antibodies to GM1 ganglioside interfere with optimal neonatal development on both dendrites and myelin in cerebral cortex. The results provide an animal model in which an immunologically-mediated disturbance of cortical development is associated with chronic behavioral impairment.

Clearance of macromolecular and particulate substances from the cerebrospinal fluid system of the rat.

Arachnoid villi in the intracranial dural sinuses constitute the principal sites for absorption of proteins and particulates from the cerebrospinal fluid (CSF) system. Although arachnoid villi in the rat are morphologically less complex than those found in other mammals, their resistance to CSF outflow, as assessed by a graded series of contstant flow manometric infusions, is similar to that found in other species. Moreover, inulin and polystyrene beads, when infused into the spinal subarachnoid space of rats, are rapidly cleared from the CSF system into intracranial dural sinuses. Inulin appeared in sinus blood 3 minutes after onset of infusion and reached concentrations 26 times greater than those found in the systemic circulation; particulate matter in the form of 0.5 micrometer polystyrene beads showed similar efflux characteristics. Hence, the CSF system of the rat is functionally similar to that found in other mammalian species, with arachnoid villi constituting a major efflux route for clearance of macromolecular and particulate substances.

Regulation of intracranial pressure in rat, dog, and man.

Intracranial resistance and compliance were assessed in the cerebrospinal fluid system of rat, dog, and man by means of low-volume, short-duration infusions of artificial CSF into the subarachnoid space. A family of pressure/time response curves was obtained for each species: at low flow rates, steady-state pressure elevations were associated with normal neurological function; at high flow rates, rapid linear pressure elevations were associated with marked neurological dysfunction. From these curves a mathematical model was developed which describes transport and pressure-dependent valvelike characteristics of the CSF outflow resistance. This resistance shows a progressive phylogenetic change in rat, dog, and man which increasingly enhances the species' abilities to vent fluid from the intracranial cavity into the venous circulation. Arachnoid villi appear to be the major structures modulating sustained, nonlethal elevations of intracranial pressure.

Intracranial pressure regulation: a comparative model of cerebrospinal fluid systems.

A comparative model of the cerebrospinal fluid (CSF) system in rat, dog and man was derived from manometric data using low volume, short duration infusions into the subarchanoid space in order to describe the mechanisms governing intracranial pressure dynamics. The mathematical model indicates that steady-state elevations of intracranial pressure are regulated primarily by a nonlinear, pressure dependent outflow resistance to CSF reabsorption. While the form of the resistance relationship is similar for the three species tested, differences in the magnitude of CSF outflow parameters are apparent. Model stimulation on a digital computer suggests that parameter changes within the resistance relationship can have a profound effect on the intracranial pressure. In contrast, intracranial compliance acts only to buffer transient changes in volume prior to the establishment of steady-state CSF pressures.