Neonatal capsaicin treatment results in prolonged mitochondrial damage and delayed cell death of B cells in the rat trigeminal ganglia.

Capsaicin acts on the vanilloid receptor subtype 1, a noxious heat-gated cation channel located on a major subgroup of nociceptive primary afferent neurons. Following the systemic capsaicin treatment of neonatal rats, the loss of B-type sensory neurons in trigeminal ganglion of adult rats with chemoanalgesia and abolition of neurogenic inflammation was investigated. Our quantitative morphometric analysis revealed that in the trigeminal ganglion of neonatal rats treated with 50 mg/kg s.c. capsaicin, the total number of neurons, morphology of B-type cells and cell-size histograms did not differ from that of the controls 1 or 5 days after treatment. These observations indicate that early cell death does not play a significant part in the loss of B-type cells, which in our sample was 39.4% on the 19th day. However under the electron microscope pronounced selective mitochondrial swelling with disorganized cristae was observed in B-type neurons at 1-20 weeks after capsaicin treatment. Daily treatment with nerve growth factor (NGF, 10 x 100 microg/kg s.c.), started 1 day after capsaicin injection, prevented the loss of B-type cells but did not counteract the development of long-lasting mitochondrial damage. After NGF treatment, partial restitution of chemonociception to capsaicin instillation into the eye occurred but capsaicin-induced inhibition of neurogenic plasma extravasation in the hindpaw evoked by topical application of mustard oil remained unaltered. We conclude, that capsaicin treatment in neonatal rats, as in the adults, destroys terminal parts of the sensory neurons supplied by vanilloid receptors and induces long-lasting mitochondrial swelling in the soma. We hypothesize that loss of NGF uptake results in delayed cell death of B-type neurons in neonates.

Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy.

The goal of the present study was to determine whether alumina gel injections into temporal lobe structures cause complex partial seizures (CPS) and pathological changes observed in human temporal lobe epilepsy. Rhesus monkeys with alumina gel injections in the amygdala, perirhinal and entorhinal cortices, or Ammon's horn and dentate gyrus all initially displayed focal pathological electroencephalographic (EEG) slowing limited to the site of injection. After clinical seizures developed, they also displayed widespread pathological EEG slowing over both hemispheres, interictal and ictal epileptiform EEG abnormalities limited to the mesial-inferior temporal lobe on the side of injection, and different degrees of spread to other ipsilateral and contralateral structures. Noninjected control and nonepileptic monkeys with injections into the middle and inferior temporal gyri displayed no hippocampal neuronal loss or mossy fiber sprouting. When alumina gel was injected into the amygdala, CPS began within 3-6 weeks and degeneration of neurons and gliosis occurred in the perirhinal cortex or the hippocampus, with consequent sprouting of mossy fibers in the dentate gyrus. Dispersion of the granule cell layer was also observed. Other monkeys with alumina gel in the perirhinal and entorhinal cortices developed CPS within 2-3 weeks after the injections and displayed mossy fiber sprouting only after 4 weeks after the injections. Alumina gel in Ammon's horn and the dentate gyrus also induced CPS, but mossy fiber sprouting was limited to sites immediately adjacent to the injection, probably because none survived more than 4 weeks after the injections. This nonhuman primate model of CPS displayed similar anatomical, behavioral, and EEG features as observed in human temporal lobe epilepsy and provides opportunities to analyze the chronological sequence of epileptogenesis and to test potential therapies.

Postnatal neurogenesis in the rat hypothalamus.

Neurogenesis of the rat hypothalamus was studied with the [3H]thymidine autoradiography method during the first postnatal month. In the parvicellular hypothalamic nuclei a low rate (1%) of neurogenesis could be observed during the first postnatal week, but not later. There was no sign of neuron formation in the magnocellular cell groups. A number of glial cells were labeled throughout the first month in all hypothalamic nuclei at a decreasing rate. Therefore, birth is not a sharp dividing line in the neurogenesis of the hypothalamus in the rat.

Divergent responses to thyroid hormone treatment of the different secondary germinal layers in the postnatal rat brain.

The effect of daily triiodothyronine (T3) treatment (first injection on the day of birth) was studied on the postnatal development of various parts of the rat brain. It was found that the T3 treatment resulted in an increase of the cell multiplication in the external grannular layer of the cerebellum but decreased the cell division or had no significant effect in the periventricular germinal layer and in the polymorph layer of the dentate gyrus. From the 10th day the T3 treatment resulted in a decrease of the cell division in all secondary germinal layers examined. As a reason for this different effect is can be suggested that the triidothyronine acts differently upon the various neuronal and glial precursors or upon the germinal layers producing them.