Brain research
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In order to investigate whether cholera toxin B subunit (CTb) is transported by unmyelinated primary afferents following nerve injury, we transected the sciatic nerves of six rats, and injected the transected nerves (and in three cases also the intact contralateral nerves) with CTb, 2 weeks later. The relationship between CTb and two neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was then examined in neurons in the ipsilateral L4 and L5 dorsal root ganglia, using immunofluorescence staining and confocal microscopy. We also immunostained sections of spinal cord and caudal medulla for CTb, NPY and VIP. ⋯ The main finding of the present study was that almost all of the VIP- (96%) and NPY- (98%) positive neurons in the dorsal root ganglia on the lesioned side were also CTb-labelled. After nerve injury VIP is upregulated in fine afferents that terminate in laminae I and II, and most of these probably have unmyelinated axons. Since the cell bodies of these neurons were labelled with CTb that had been injected into the transected sciatic nerve, this suggests that many of these fine afferents, which do not normally transport CTb, are capable of doing so after injury.
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The aim of the present study was to examine the effect of intrathecal (i.t.) injection of pertussis toxin (PTX) on the nociceptive threshold and protein kinase C (PKC) expression in the rat spinal cord. The role of N-methyl-D-aspartic acid (NMDA) receptors in these changes was also examined. Male Wistar rats were implanted with two i.t. catheters, one of which was connected to a mini-osmotic pump and used to infuse saline or D-2-amino-5-phosphonopentanoic acid (D-AP5) (2 microg/h) starting on day 3 after i.t. catheter insertion. ⋯ Infusion of the NMDA antagonist, D-AP5, prevented both the thermal hyperalgesia and the increase in PKCgamma isoform expression in PTX-treated rats, and had no effect on these values in nai;ve rats. Intrathecal injection of the PKC inhibitor, chelerythrine (10 microg), significantly inhibited the thermal hyperalgesia observed in PTX-treated rats. These results show that i.t. injection of PTX induced thermal hyperalgesia accompanied by a selective increase in PKCgamma expression in both the synaptosomal membrane and cytosolic fractions of the dorsal horn of the rat lumbar spinal cord, and both effects were inhibited by the NMDA receptor antagonist, D-AP5.
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Reactive oxygen species-induced reperfusion injury of the brain is an important cause of neonatal morbidity and mortality following perinatal hypoxia-ischemia. Deferoxamine, allopurinol and oxypurinol have previously been shown to be neuroprotective in vivo during or directly after hypoxia-ischemia. To further characterize and more precisely elucidate whether the neuroprotective properties of these agents are mediated via neuronal and glial cells, or whether endothelial cells contribute to this effect, we tested their ability to protect CA1 neurons in organotypic hippocampal slices. ⋯ As expected, 89% and 98% protection was demonstrated with dizocilpine present during or during/after oxygen/glucose deprivation resp. alpha-Phenyl-N-tert-butyl nitrone administered during/after oxygen/glucose deprivation provided 44% protection. However, iron chelation with deferoxamine and inhibition of xanthine oxidase by allopurinol or oxypurinol did not confer neuroprotection. The neuroprotective effect of deferoxamine, allopurinol or oxypurinol, as seen in vivo, may be obtained via inhibition of the production of damaging factors by blood born substances or endothelial cells.
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Neuropathic pain is a common clinical problem with complex aetiology, mechanisms and symptoms. Alterations in spinal gamma-aminobutyric acid (GABA) receptors may contribute to persistent pain states. The aim of the present study is to investigate potential changes of spinal GABA(A)-receptor function following peripheral nerve injury. ⋯ Following either sham surgery, or spinal nerve ligation, spinal muscimol inhibited Abeta-, Adelta- and C-fibre evoked responses of spinal neurones to a similar extent, however significant inhibitory effects on the post-discharge response were not observed in nerve injured rats. Our data demonstrate that GABA(A)-receptor control of Abeta- and Adelta-fibre evoked responses are not altered in nerve injured or sham operated rats, compared to control. However, following nerve injury we report a reduction in GABA(A)-receptor control of C-fibre responses, in particular in relation to post-discharge responses.
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The current investigation examines the significance of estrogen in central cardiovascular regulatory nuclei in modulating autonomic tone and baroreceptor reflex function. Experiments were done in anaesthetized male Sprague-Dawley rats. Changes in autonomic tone were assessed by monitoring vagal and renal efferent nerve activities before and following bilateral injection of estrogen into select central autonomic nuclei. ⋯ Pre-injection of lidocaine into the PBN resulted in complete blockade of the autonomic changes observed following estrogen injection into the CNA but did not affect the changes observed following estrogen injection into the LHA. These results suggest that estrogen acting in forebrain and midbrain cardiovascular nuclei activated efferent pathways which synapse in the LHA, CNA and/or PBN prior to projecting to autonomic preganglionic nuclei to affect autonomic tone. These nuclei may therefore provide an added level of processing and/or integration of the autonomic response(s) following activation by local or systemic estrogen.