Table 1 Studies included in systematic review
Study | Animal model | Duration of compensation | Recording type | Sample size | Outcome measure | Notable features |
|---|---|---|---|---|---|---|
de Waele 1994 [24] | Rat, UL via ischaemia (photocoagulation of the pterygopalatine artery) and mechanical disruption, compared to unoperated control | 5 h 3 days 3 weeks | Visual identification of cells labelled with antisense oligonucleotides against NMDA or metabotropic glutamate receptor | Control—6 animals 5 h—6 animals 3 days—unclear, possibly 3 animals 3 weeks—6 animals | Number of silver grains per cell, silver grain density in cells | Success of UL was assessed behaviourally; however, the number of excluded animals was not reported. There was inconsistent reporting animal numbers per experimental group in the methods and results. |
Cameron 1997 [15](*) | Rat, UL via 100% ethanol injection, compared to sham-operated control | 2 h 4 h 6 h 1 day 2 days | (Presumed) Extracellular recordings, ipsilesional | Control—5 animals, 2 sham-operated, number undergoing UL unclear 4 h—32 cells 6 h—43 cells 24 h—36 cells 2 h—unclear 48 h—unclear | Mean spontaneous discharge rate (spikes/s) | Sprague-Dawley rats used for experimentation were at the lower end of maturity (60–120 g) raising concerns about developmental stage. There was selective reporting of outcomes, with 2 and 48 h rates reported graphically rather than numerically. |
Cameron 1999 [16](*) | Rat, UL via 100% ethanol injection, compared to sham-operated control | 4 h 6 h | Single unit extracellular recordings, ipsilesional | Control—9 sham-operated, 41 neurons UL—9 animals, 61 neurons | Mean spontaneous discharge rate (spikes/s) | The type of animal and their baseline characteristics such as sex and age were not stated in the report. Additional interventions were studied—no withdrawal of anaesthesia following labyrinthectomy, and administration of dexamethasone or dexamethasone antagonist. |
Vibert 1999 [25] | Guinea pig, UL via mechanical disruption, compared to unoperated control | 1 day 3-7 days (pooled following analysis) | Single unit extracellular recordings and field potentials, ipsilesional and contralesional | Total of 65 animals 1 day—14 animals 3 days—26 animals 5 days—10 animals 7 days—15 animals | Mean spontaneous discharge rate (spikes/s), evoked field potentials following stimulation of the vestibular and abducens nerves | An unclear number of animals were excluded the stated reason being the difficulty of the surgical procedure yielding ‘unusable data’. |
Yamanaka 2000 [14] (*) | Rat, UL via ethanol injection, compared to unoperated control | 4 h | Extracellular whole cell, ipsilesional | Control—28 animals, 77 cells 4 h—44 animals, 126 cells | Mean spontaneous discharge rate (spikes/s), dose of GABA agonist required to inhibit tonic resting activity | Rostral and caudal MVN neurons were analysed separately in the study and therefore analysed separately in the meta-analysis. |
Him 2001 [18] (*) | Rat, UL via 100% ethanol injection, compared to normal | 1-3 days 7-10 days | Intracellular patch clamp, ipsilesional | Control—44 animals 1-3 day—34 animals, 90 cells 7-10 day—25 animals, 84 cells | Mean spontaneous discharge rate (spikes/s), action potential morphology | Inclusion criteria are mentioned however never explicitly stated. Some data is lost without being accounted for. |
Johnston 2001 [26] (*) | Rat, UL via 100% ethanol injection, compared to normal | 4 h 1 day 2 days 7-10 days | Single unit extracellular recordings, ipsilesional | Control—25 cells 2 days—42 cells 7-10 days—40 cells Unclear how many animals in control group or underwent UL | Mean spontaneous discharge rate (spikes/s) | Control, 4 and 24 h data was obtained from a previous study and therefore not included in the current set of data. |
Ris 2001 (*) | Guinea pig, UL via mechanical disruption, compared to normal | 2 days 7 days | Single unit extracellular recordings, ipsilesional | Control—10 animals, 57 cells 2 days—6 animals, 118 cells 7-10 days—6 animals, 159 cells | Number of spontaneously active neurons, mean spontaneous discharge rate (spikes/s) | A potentially ototoxic antibiotic was given during the surgical procedure (aminoglycoside class) however such a short duration of exposure is unlikely to have any significant effect. |
Johnston 2002 [27] | Rat, UL via 100% ethanol injection, compared to normal and flocculectomised animals | 4 h 2 days | Single unit extracellular recordings, ipsilesional | Control—5 animals, 189 cells 4 h—5 animals, 187 cells 2 days—5 animals, 126 cells | Mean spontaneous discharge rate (spikes/s) | Numerical data could not be extracted in sufficient detail as it was presented graphically. Therefore, it was excluded from the meta-analysis. |
Ris 2002 [28] | Guinea pig, UL via mechanical disruption and ototoxic antibiotic injection, compared to normal | 7 days | Intracellular patch clamp recordings, ipsilesional | Control—38 cells 7 days—38 cells | Gain (spikes/s/nA), dynamic responsiveness (maximal firing rate compared to steady-state rate) | Unclear how many animals were used in the experiment. All recordings in the presence of synaptic antagonists, held from a hyperpolarised membrane potential to abolish spontaneous discharge. |
Patko 2003 [29] | Rats, UL by mechanical disruption, compared to unoperated controls | 1 day 3 days 8 days 30 days | In situ hybridisation using mRNA probes to sodium and potassium channels | Total—42 rats 3 rats for each channel and time point | Optical density of labelling | There was no evidence to suggest changes in the abundance of these channels to explain the observed changes in excitability. |
Ris 2003 [30] | Guinea pig, UL via mechanical disruption and ototoxic antibiotic injection, compared to normal | 7 days | Intracellular patch clamp recordings, ipsilesional; immunohistochemistry labelling calcium channel proteins | Control—28 animals, 41 cells 7 days—21 animals, 43 cells | Spike discharge characteristics; changes in immunohistochemical staining patterns | An increase in low threshold spiking type activity was observed in all neurons, without a detectable change in the immunolabelling of protein subunits of T-type calcium channels. |
Eleore 2004 | Rat, UL via mechanical disruption, compared to unoperated control | 5 h 1 day 3 days 8 days 1 month 2 months | In situ hybridisation using mRNA probes to glycine receptor subunits and an anchor protein gephyrin, detected using autoradiography or immunofluorescence | Total—60 rats Control—12 animals, 6 used in final analysis Experimental—48 animals, 36 used in final analysis, with 3 animals per experimental group | Optical density of labelling; intensity of immunofluorescence | The discrepancy between the original number of animals included in each group and the number used in the final analysis is presumed to be due to exclusion because of failure to compensate post labyrinthectomy; however, this is not explicitly stated. |
Guilding 2004 | Rat, UL via 100% ethanol injection, compared to sham-operated control | 4 h | Thin-layer chromatography quantified by optical densitometry | Control—16 animals 4 h—16 animals | Change in density on chromatography | No differences in the expression of an enzyme involved in the production of glucocorticoids following labyrinthectomy. |
Guilding 2005 [31] | Rat, UL via ethanol injection, compared to unoperated control | 4 h 2 days 7 days | Extracellular whole cell recordings, ipsilesional, before and after application of a cocktail of neurotransmitter antagonists (for blockade of GABAA, GABAB, glycine, AMPA and NMDA receptors) | Unclear how many animals were used in experiment control—85 cells, 75 cells synaptic blockade 4 h—76 cells, 70 cells synaptic blockade 48 h—82 cells, 80 cells synaptic blockade 7 days—90 cells, 90 cells synaptic blockade | Mean spontaneous discharge rate (spikes/s) | Rostral and caudal MVN neurons were analysed separately in the study. Numerical data could not be extracted in sufficient detail from the study for inclusion in the meta-analysis as it was presented graphically. |
Nelson 2017 [19] | Mouse, UL via mechanical disruption, compared to sham-operated control | 1 day 3 days 1 week 3 weeks | Intracellular patch clamp, ipsilesional; ion channel protein expression; ocular videography | At least 6 animals 8 h -140 control, 156 UL cells 1 day—142 control, 131 UL cells 3 days—91 control, 112 UL cells 7 days—96 control, 105 UL cells 21 days—63 control, 62 UL cells | Mean spontaneous discharge rate (spikes/s), gain (spikes/s/nA), firing rate potentiation | This was the only study to blind intervention allocation from investigators. It was unclear how many animals were used throughout the experiment and how many were in each experimental group. |