PubMed · 9893534
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M Morgan. 1998. 'Retrospective soliloque'.. https://doi.org/10.1046/j.1365-2044.1998.00684.x
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Multiple sensory inputs to the superior colliculus (SC) play an important role in guiding head and eye movements toward or away from biologically significant stimuli. Much is now known about the visual, auditory, and somatosensory response properties of SC neurones that mediate these behavioural reactions. Rather less is known about the responses of SC neurones to noxious stimuli, and thus far, most of this information has been obtained in anaesthetised animals. Therefore, the purpose of the present study was to use the c-fos immunohistochemical technique and standard extracellular electrophysiology as parallel measures of nociceptive activity in the SC under different conditions of anaesthesia. In unanaesthetised animals, experimental and control treatments induced a qualitatively similar pattern of Fos-like immunoreactivity (FLI) in the SC, which was quantitatively related to the severity or biologic salience of the treatment; thus, baseline control < control injections of saline < a nonpainful stressor (immobilisation) < noxious injections of formalin. Compared with baseline levels, urethane and avertin anaesthesia induced FLI expression in the SC intermediate layers, although the FLI response to both noxious stimulation and control conditions was differentially suppressed in different layers of the SC by anaesthesia. Parallel electrophysiologic recordings found that anaesthesia was associated with high levels of spontaneous activity in the SC intermediate layers, often in neurones which were also nociceptive. High rates of background spike activity were also induced in the SC intermediate layers by noxious stimulation in chronically recorded awake animals. Although these results point to some differences between the nociceptive responses of SC neurones in anaesthetised and unanaesthetised animals, both data sets support the view that there are different populations of nociceptive neurones in the rodent SC that may be related to different adaptive functions of pain.
We investigated whether components from the rat Vx-MLAEP could be used to assess depth of anaesthesia induced by propofol. Propofol decreased MLAEP amplitudes and increased latencies. We propose that the P(16)-N(22) wave in the rat MLAEP is similar to the human P1, and that recovery of this wave during propofol anaesthesia correlates with behavioural measures of the regaining of consciousness.
For progression to clinical trials in stroke, putative neuroprotective compounds should show robust efficacy post-ischaemia in several experimental models of stroke. This paper describes the characterisation of (+)(1S, 2R)-cis-1-[4-(1-methyl-1-phenylethyl)phenoxy]-2-methylamino indane hydrochloride (SB-221420-A), a Ca(2+) and Na(+) channel antagonist. SB-221420-A inhibited (IC(50)=2.2 microM) N-type voltage-operated Ca(2+) channel currents in cultured superior cervical ganglion neurons, which were pretreated with 10 microM nimodipine to block L-type voltage-operated Ca(2+) channel currents. In dorsal root ganglion neurons pretreated with 1 microM omega-conotoxin GVIA to block N-type voltage-operated Ca(2+) channel currents, SB-221420-A inhibited the residual Ca(2+) current with an IC(50) of 7 microM. SB-221420-A also inhibited Na(+) currents in dorsal root ganglion neurons with an IC(50) of 8 microM. In rats, the pharmacokinetic profile of SB-221420-A shows that it has a half-life of 6.4 h, a high volume of distribution, is highly brain penetrating, and has no persistent metabolites. Following bilateral carotid artery occlusion in gerbils, SB-221420-A significantly reduced the level of ischaemia-induced hyperlocomotor activity and the extent of hippocampal CA1 cell loss compared to the ischaemic vehicle-treated group. SB-221420-A was also effective in focal models of ischaemia. In the mouse permanent middle cerebral artery occlusion model, SB-221420-A (10 mg/kg) administered intravenously, post-ischaemia significantly (P<0.05) reduced lesion volume compared to the ischaemic vehicle-treated group. In the normotensive rat permanent middle cerebral artery occlusion model, SB-221420-A (10 mg/kg) administered intravenously over 1 h, beginning 30 min postmiddle cerebral artery occlusion, significantly (P<0.05) reduced lesion volume from 291+/-16 to 153+/-30 mm(3), compared to ischaemic vehicle-treated controls when measured 24 h postmiddle cerebral artery occlusion. Efficacy was maintained when the same total dose of SB-221420-A was infused over a 6-h period, beginning 30 min postmiddle cerebral artery occlusion. SB-221420-A also significantly (P<0.05) reduced lesion volume following transient middle cerebral artery occlusion in normotensive rats and permanent middle cerebral artery occlusion in spontaneously hypertensive rats (SHR). Investigation of the side effect profile using the Irwin screen in mice revealed that, at neuroprotective doses, there were no overt behavioural or cardiovascular changes. These data demonstrate that robust neuroprotection can be seen post-ischaemia with SB-221420-A in both global and focal ischaemia with no adverse effects at neuroprotective doses, and indicate the potential utility of a mixed cation blocker to improve outcome in cerebral ischaemia.