Associations between the human growth hormone-releasing hormone- and neuropeptide-Y-immunoreactive systems in the human diencephalon: a possible morphological substrate of the impact of stress on growth.

Previous studies revealed that stress is a pivotal factor in the regulation of growth. Psychological harassment may result in psychosocial dwarfism with delayed puberty, short stature and depression. Growth hormone (GH) secretion is suppressed by stress, possibly via the attenuation of growth hormone-releasing hormone (GHRH) secretion. However, the morphological substrate of this phenomenon has not been elucidated yet. Since neuropeptide Y (NPY) levels in the plasma is increased by administration of various stressors, the common consensus is that NPY plays a crucial role in the stress response. In the present study, we examined the putative juxtapositions between the NPY- and GHRH-immunoreactive (IR) systems in the human hypothalamus using double-label immunohistochemistry. Our findings revealed that the majority of the GHRH-IR perikarya formed intimate associations with NPY-IR fiber varicosities. The majority of these juxtapositions were found in the infundibular nucleus/median eminence where NPY-IR fiber varicosities often covered a significant surface area of the GHRH neurons. Since the juxtapositions between the GHRH-IR perikarya and NPY-IR fiber varicosities may be functional synapses, they may represent the morphological substrate of stress-suppressed GH secretion. The large number of contacting elements indicates that NPY plays a pivotal role in GH release, and may be considered as a major factor in the attenuation of growth by stress in humans.

Early activation of inhibitory neurons in the thalamic reticular nucleus during focal neocortical seizures.

The neurons of the thalamic reticular nucleus are among the main targets of corticothalamic projections and their vulnerability in pathological conditions is well established. The present experiments aimed at the description and immunocytochemical characterization of the neurons of the thalamic reticular nucleus activated in neocortical seizures. Focal seizures were induced by the topical application of isotonic, isohydric 4-aminopyridine solution to the sensorimotor neocortex of adult, anesthetized Wistar rats. The animals were perfused with fixative after 1 and 2 h of recorded seizure activity. Coronal plane vibratome sections were incubated with cocktails of polyclonal c-fos and monoclonal parvalbumin antisera. Labeled cells in the thalamic reticular nucleus were counted and related to total cell counts. Neurons and neuropil showed strong parvalbumin immunoreactivity. Double-stained sections revealed that 55.32% of the parvalbumin-positive cell population expressed c-fos protein in their cell nuclei at the end of the 1 h seizure period. This ratio decreased to 43.5% following 2 h seizure. Labeled cells, although less in number were also observed in the contralateral thalamic reticular nucleus. Since parvalbumin labels GABAergic cells, it is tempting to speculate that this activation of intrathalamic inhibiton might exert an important anticonvulsant protection on other thalamic nuclei.

Alterations of dorsal root potential in the course of transganglionic degenerative atrophy.

Alterations in the dorsal root potential (DRP) which was evoked by stimulation of the common peroneal nerve of the rat, have been studied in the course of transganglionic degenerative atrophy (TDA) of primary sensory terminals in the upper dorsal horn. TDA was induced by perineural application of Vinca alkaloids around the sciatic nerve. In 9 to 30 days after this treatment, latency of DRP increased, whereas its amplitude and duration decreased. In this period, no C fibre response could be elicited. As a possible mechanism underlying the alterations of DRP, the functional consequences of atrophic changes of primary central afferent terminals are being discussed in terms of the close correlation between structure and function and the possible inferences of the electrophysiological reaction to the therapeutic application of Vinca alkaloids in the iontophoretic treatment of chronic intractable pain.

Effects of perineurally applied cytostatic, cytotoxic and chelating agents upon peripheral and central processes of primary nociceptive neurons.

After perineural application, the effects of mannomustine, cyclophosphamide, tetrameskylmannite, 6-mercaptopurine, azathioprine and d-penicillamine upon structure of peripheral nerves and the substantia gelatinosa Rolandi were studied by means of neurohistochemical techniques and compared to those of the microtubule inhibitors Vinblastine, Vincristine and colchicine. While the cytostatic and cytotoxic drugs induced only sporadic degeneration in the structure of the peripheral nerve and, accordingly, caused only a minor extent of transganglionic degenerative atrophy in the Rolando substance, the chelating agent d-penicillamine causes massive Wallerian degeneration after perineural application and, consequently, induces an extensive degenerative atrophy in the Rolando substance. The destructive effect of d-penicillamine upon conduction properties of the impaired nerve has been established also by means of electrophysiological recording. All the drugs studied differ fundamentally from microtubule inhibitors like the Vinca alcaloids that, by virtue of their blocking effect of axoplasmic transport, induce degenerative atrophy in the Rolando substance after perineural application without causing Wallerian degeneration in the peripheral nerve. Accordingly Vinca alcaloids are the most promising candidates as locally applied therapeutics in intractable pain.

Perineural microtubule inhibitors induce degenerative atrophy of central nociceptive terminals in the Rolando substance.

Short-term perineural application of a microtubule inhibitor around a peripheral nerve induces degenerative atrophy of primary central nociceptive terminals in the Rolando substance. Consequences of the local microtubule inhibitor treatment are identical, both at light- and electron microscopic levels, with those that follow transection of a peripheral nerve. Degenerative atrophy in the Rolando substance is due to arrested axoplasmic transport in, and not to Wallerian degeneration of, the peripheral axons since (1) locally applied vinblastine and vincristone do not induce peripheral degeneration at all and (2) even though local colchicine treatment may cause Wallerian degeneration of thick myelinated axons, thin Adelta and C fibers do not undergo degeneration after colchicine treatment. The intriguing possibility to use this approach in the treatment of intractable pain is discussed.

The frequency dependence of evoked and postsynaptic potentials in the somatosensory cortex of the cat.

Intracellular records were made from neurones of the somatosensory cortex of cats, during stimulation of the ventrobasal complex of the thalamus. The aim of the experiments was to detect correlations between frequency dependence of surface evoked potentials and that of unit discharges. The amplitude of the surface evoked potential showed a strong diminution when the frequency of the thalamic stimulation was raised from 1 cps to 15 cps. In spite of this, frequency dependence in amplitude of unit discharges was never seen. As regards their frequency of occurrence the unit responses (full spikes, dendritic, postsynaptic potentials) behaved differently: a part of them showed increasing, another part gave decreasing occurrence, and the remaining portion did not change it. The authors conclude that temporal dispersion fails to give account for the frequency dependence, therefore further possibilities have to be examined.