Experimental neurology
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Experimental neurology · Jun 1998
Plastic changes in glycine and GABA release and uptake in adult brain stem auditory nuclei after unilateral middle ear ossicle removal and cochlear ablation.
[i] In young adult guinea pigs, the effects of unilateral ossicle removal and unilateral cochlear ablation were determined on [14C]glycine or [14C]GABA release and uptake measured in subdivisions of the cochlear nucleus (CN), the superior olivary complex, and the auditory midbrain, after 2 or 5, 59, and 145 postlesion days. Activities were compared to those of age-matched, unlesioned controls. [ii] [14C]Glycine release declined bilaterally in the anteroventral and dorsal CN after ossicle removal and in the dorsal CN after cochlear ablation. [iii] Transient elevations of release occurred at 59 days in the ipsilateral posteroventral CN ([14C]glycine) and bilaterally in the ventral nucleus of the lateral lemniscus ([14C]GABA) after ossicle removal, and bilaterally in the medial superior olive ([14C]glycine) after cochlear ablation. [iv] In the medial nucleus of the trapezoid body, [14C]GABA release was depressed bilaterally 5 days after ossicle removal, but was elevated at 145 days contralaterally after ossicle removal and ipsilaterally after cochlear ablation. [v] In the contralateral central nucleus of the inferior colliculus, [14C]GABA release was elevated persistently after ossicle removal. After cochlear ablation, release was elevated at 5 days, near the control at 59 days, and elevated again at 145 days. [vi] After both lesions, [14C]glycine uptake was elevated bilaterally in the CN and medial superior olive. [14C]GABA uptake became depressed by 59 or 145 days bilaterally in the auditory midbrain. [vii] These changes may stem from regulation and may contribute to mechanisms that generate symptoms such as loudness recruitment and tinnitus, which often accompany hearing loss.
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Experimental neurology · May 1998
The effects of NGF and sensory nerve stimulation on collateral sprouting and gene expression in adult sensory neurons.
Collateral sprouting of mature cutaneous nociceptive fibers is regulated by the availability of NGF, and the onset of this sprouting can be accelerated by electrical stimulation of the intact nerve. To investigate this influence of stimulation on NGF-induced sprouting, the thoracic dorsal cutaneous nerves of adult rats were exposed and those on the left side of the animals were electrically stimulated. NGF was then administered daily for 1-12 days. ⋯ The NGF treatment resulted in the upregulation of BDNF mRNA to peak levels within the first 2 days of treatment, although the electrical stimulation had little additional effect. These results demonstrate that exogenously supplied NGF itself can elicit sprouting from intact cutaneous nociceptive afferents and that electrical stimulation further influences the expression of mRNAs involved in the sprouting response. While the increases in NGF receptors and GAP-43 mRNA have been shown to be associated with collateral sprouting, the role of BDNF is not clear, but may be involved in altered sensory processing (i.e., hyperalgesia) that has been shown to occur subsequent to NGF administration.
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Experimental neurology · May 1998
Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1.
Recent evidence points to a role of cytokines like tumor necrosis factor-alpha (TNF) in the generation of hyperalgesia not only in inflammatory, but also in neuropathic pain. We used the model of chronic constrictive injury (CCI) of one sciatic nerve in the mouse to investigate which of the two known TNF receptors is involved in the process that leads to hyperalgesia after nerve injury. ⋯ Neutralizing antibodies to TNFR2 had no effect. We conclude that TNFR1, but not TNFR2, is mediating thermal hyperalgesia and mechanical allodynia after nerve injury.
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Experimental neurology · Apr 1998
Ciliary neurotrophic factor stimulates astroglial hypertrophy in vivo and in vitro.
After insult or trauma, astrocytes become activated and endeavor to restore the brain's delicately balanced microenvironment. An index of their activated state is that they become enlarged or hypertrophic. Ciliary neurotrophic factor (CNTF), a member of the alpha helical family of cytokines, is synthesized by astrocytes and is generally regarded to be an autocrine and paracrine injury signal. ⋯ W. Levison et al., 1996; Exp. Neurol. 141, 256), we conclude that CNTF is a powerful activator of astrocytes and that it is likely responsible for the persistent glial hypertrophy observed following injuries and diseases of the CNS.
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Experimental neurology · Mar 1998
Comparative StudyComparison of more and less lipophilic serotonin (5HT1B/1D) agonists in a model of trigeminovascular nociception in cat.
The trigeminovascular system consists of bipolar neurons innervating pain-producing intracranial structures, such as the superior sagittal sinus (SSS), and projecting to the medullary and upper cervical dorsal horn second order neurons. Zolmitriptan is a newly developed 5HT1B/1D receptor agonist with both peripheral and central sites of action in the trigeminovascular system due to greater lipophilicity relative to the more hydrophilic antimigraine compound sumatriptan. Given that we have seen electrophysiological and autoradiographic binding data to suggest that the compound may inhibit activity at second-order neurons this study was designed to examine whether such an effect could be demonstrated in a population of trigeminal neurons using Fos immunohistochemistry. ⋯ We noted a significant reduction in Fos expression after treatment with zolmitriptan but no effect with sumatriptan. Given that zolmitriptan accesses central neurons and that the method of stimulation we have employed would bypass peripheral trigeminal mechanisms it is likely that the reduction in second-order trigeminal neuronal activity was due to a direct inhibitory effect of the compound on those cells. These neurons form a possible site for the treatment of acute attacks of migraine.