Neuroscience
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Clinical studies have demonstrated that patients sustain prolonged behavioral deficits following traumatic brain injury, in some cases culminating in the cognitive and histopathological hallmarks of Alzheimer's disease. However, few studies have examined the long-term consequences of experimental traumatic brain injury. In the present study, anesthetized male Sprague-Dawley rats (n = 185) were subjected to severe lateral fluid-percussion brain injury (n = 115) or sham injury (n = 70) and evaluated up to one year post-injury for cognitive and neurological deficits and histopathological changes. ⋯ Immunohistochemistry using multiple antibodies to the amyloid precursor protein and/or amyloid precursor protein-like proteins revealed novel axonal degeneration in the striatum, corpus callosum and injured cortex up to one year post-injury and in the thalamus up to six months post-injury. Histologic evaluation of injured brains demonstrated a progressive expansion of the cortical cavity, enlargement of the lateral ventricles, deformation of the hippocampus, and thalamic calcifications. Taken together, these findings indicate that experimental traumatic brain injury can cause long-term cognitive and neurologic motor dysfunction accompanied by continuing neurodegeneration.
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In the present study we evaluated the consequences of interference with nitric oxide synthesis during development on brain function and behaviour in later life. Rat pups received a daily injection of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg, s.c.) from postnatal day 0 to 24. At postnatal day 8 L-NAME-treated rats had enlarged and heavier stomachs, while body weights appeared to be reduced. ⋯ Hence, nitric oxide synthase was inhibited whereas the soluble guanylyl cyclase activity may be increased in sensitivity. At postnatal day 24 basal cyclic GMP levels and nitric oxide-mediated cyclic GMP formation in the brain structures of L-NAME-treated rats had normal values again. Taken together, the findings of this study suggest that postnatal inhibition of nitric oxide synthase has profound neurochemical effects during development and may have short-lasting effects on non-cognitive behaviour, but it does not affect behaviour and brain function in later life.
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In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. ⋯ Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.
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Although there are numerous opioid-sensitive structures in the central nervous system, the contribution of each to the analgesic effect of systemically administered morphine is controversial. One such structure is the rostral ventromedial medulla. In the present study, we tested the hypothesis that the rostral ventromedial medulla is necessary for the full expression of systemic morphine-induced antinociception. ⋯ Additionally, in unrestrained rats, muscimol (50 ng) and cholecystokinin tetrapeptide (0.5 ng) infusion into the rostral ventromedial medulla completely reversed systemic morphine-induced analgesia, while lidocaine (0.5 microl of 4%) and cholecystokinin octapeptide (0.25 ng) infusion partially reversed systemic morphine-induced analgesia. These findings demonstrate that the rostral ventromedial medulla does not tonically modulate tail-flick latency in unrestrained rats, but does modulate tail-flick latency when animals are stressed via restraint. These findings also strongly support the hypothesis that the rostral ventromedial medulla is necessary for the full analgesic effects of systemically administered morphine.
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Fluoxetine is a serotonin re-uptake blocker commonly used to treat endogenous depression. The present experiments were carried out to assess the effects of fluoxetine on c-fos induction throughout the rat brain. In addition, intron-directed in situ hybridization analysis was used to examine fluoxetine regulation of corticotropin-releasing factor heteronuclear gene transcription in the paraventricular nucleus of the hypothalamus. ⋯ Significant changes in corticotropin-releasing factor type 1 receptor messenger RNA levels were also observed in the paraventricular nucleus but with a slow incremental biosynthesis of the receptor messenger RNA, as high levels were discernible only 360 min after fluoxetine treatment. Finally, we failed to detect sex-related differences in the acute response to fluoxetine, as both female and male rat brains showed a comparable induction of c-fos, corticotropin-releasing factor heteronuclear RNA and corticotropin-releasing factor type 1 receptor expression within parvocellular neurosecretory nerve cells that govern the stress response. All of these findings are discussed in terms of specific sequences of nuclear events that couple fluoxetine-based serotonin input with changes in gene expression in selective neurons.