Neuroscience
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The possibility that astrocytes participate in the pathophysiology of thermal brain injury caused by systemic heat exposure was examined in conscious young rats. The temporal and regional pattern of the astrocytic response to thermal injury was characterized by demonstrating the immunoreactivity of glial fibrillary acidic protein (GFAP) using monoclonal antibody and avidin-biotin complex technique. Exposure of conscious young animals to heat at 38 degrees C for 4 h in a biological oxygen demand incubator resulted in a marked increase of the GFAP immunoreactivity in specific brain regions as compared with the intact controls. ⋯ The immunostaining in general was seen in the perivascular glia, within the neuropil and the glia limitans. This increase in GFAP immunoreactivity was absent in animals exposed to the same ambient temperature (38 degrees C) for 1 h and 2 h, or at a lower temperature (36 degrees C) for 4 h. These results show that (i) astrocytes actively participate in the pathophysiology of heat stress, (ii) endogenous thermal brain injury elicits activation and hypertrophy of astrocytes ("reactive gliosis") depending on the magnitude and duration of the ambient heat stimulus, and (iii) the astrocytic reaction (observed as increased GFAP immunostaining) could be induced much more rapidly within a very short survival period of 4 h, not reported earlier.
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Comparative Study
Circuitry linking opioid-sensitive nociceptive modulatory systems in periaqueductal gray and spinal cord with rostral ventromedial medulla.
The interactions among opioid-sensitive nociceptive modulatory systems, which include the midbrain periaqueductal gray, rostral ventromedial medulla and spinal cord, are likely to play a central role in the potent antinociception that results when morphine is administered systemically. The aim of the present study was to investigate the mechanisms through which local application of morphine, either in the periaqueductal gray or at the lumbar spinal cord in the rat, influences the activity of one population of putative nociceptive modulatory neurons in rostral ventromedial medulla, i.e. "on-cells". Previous studies have shown that the spontaneous and tail-flick-related firing of on-cells is invariably depressed when morphine is given systemically in doses demonstrated to inhibit the tail-flick reflex, and that a similar depression of this activity is produced when morphine is applied directly in the periaqueductal gray or intrathecal space. ⋯ Microinjection of morphine into the periaqueductal gray blocked glutamate-evoked activity of on-cells in parallel with its suppression of the tail-flick reflex, suggesting activation of an inhibitory input to these cells. No change in glutamate-evoked activity occurred in rats in which morphine did not produce antinociception. Intrathecal administration of morphine did not alter the glutamate-evoked activity of these neurons despite blocking the tail-flick reflex, suggesting that morphine acting in the spinal cord removes an excitatory input to on-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ischemia-induced selective neuronal injury to field CA1 is not attributable to selective glutamate release in field CA1 during ischemia. Excessive release of glutamate has been proposed to play a major role in ischemia-induced selective neuronal death in field CA1 of the hippocampus. It is well known that, following carotid arterial occlusion of 5 min duration in the gerbil, the pyramidal neurons in field CA1 show delayed neuronal death, whereas the neurons in field CA3 do not show any neuronal degeneration. ⋯ No significant differences were detected in the time-course of change in glutamate release and the levels of glutamate between field CA1 and field CA3. This result indicates that the increased glutamate levels do not play a pivotal part in the detrimental effect of glutamate during 5-min ischemia. Some differentiated post-synaptic organization may act as a crucial factor in the development of ischemia-induced selective neuronal death in the gerbil hippocampus.
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Low doses (0.2-0.8 microM) of capsaicin were used to achieve selective excitation of C-fibres and the consequent synaptic activation of dorsal horn neurons (laminae I-VI) in the spinal cord of the 12-20-day-old mouse, maintained in vitro. Most dorsal horn cells were activated by application of capsaicin to dorsal root ganglia. The response consisted of a long-lasting membrane depolarization with increased regenerative (synaptic) activity in 79% of the cells, and in a further 7% only an increased synaptic activity was evoked. ⋯ This effect was paralleled with the loss of the prolonged (-)-2-amino-5-phosphonovaleric acid-sensitive phase of the excitatory postsynaptic potential evoked by the high-intensity electrical stimulation of dorsal roots. This observation suggested that activation of the N-methyl-D-aspartate receptors in the dorsal horn can be activated by small-calibre capsaicin-sensitive fibres. In summary, our data suggest that the selective activation of C-fibre afferents with capsaicin produces synaptic activity in the dorsal horn which has a strong excitatory amino acid component as well as a non-excitatory amino acid, possibly peptidergic, component.
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The transmitter mechanism of a long-lasting descending inhibition of the monosynaptic reflex was investigated in the isolated spinal cord of the neonatal rat. The monosynaptic reflex elicited by dorsal root stimulation was recorded extracellularly from a lumbar ventral root (L3-L5). Electrical stimulation of the upper thoracic part of the hemisected cord caused an inhibition lasting about 40 s of the monosynaptic reflex. ⋯ Besides ketanserin, the descending inhibition was blocked by ritanserin, haloperidol, and pipamperone, which have affinities to 5-hydroxytryptamine2 receptors, and also by spiperone and methiothepin, which are antagonists at both 5-hydroxytryptamine1 and 5-hydroxytryptamine2 receptors (all 1 microM). On the other hand, a 5-hydroxytryptamine1C and 5-hydroxytryptamine2 antagonist, mesulergine (1 microM), and 5-hydroxytryptamine3 antagonists, ICS 205-930 and quipazine (both 1 microM), did not depress either the descending inhibition or the 5-hydroxytryptamine-evoked inhibition of the monosynaptic reflex. The results with these antagonists favor the involvement of 5-hydroxytryptamine2 receptors although the results with mesulergine disagree with this notion. 5-Hydroxytryptamine1 agonists, such as 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, and 5-carboxyamidotryptamine, and a 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine, induced a long-lasting inhibition of the monosynaptic reflex, which was blocked by ketanserin whereas a 5-hydroxytryptamine2 agonist, S-(+)-alpha-methyl-5-hydroxytryptamine, evoked a biphasic inhibition, in which only the later component was blocked by ketanserin.(ABSTRACT TRUNCATED AT 400 WORDS)