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The acellular dermal matrix (ADM) and turbinate flap (TF) have been widely used in the reconstruction of skull base defects. However, owing to the lack of reported data, the therapeutic effects have been controversial. The purpose of the present study was to compare the effect of the ADM and TF on cerebrospinal fluid (CSF) rhinorrhea after nasal endoscopic resection of a skull base tumor. The data from 46 patients who had undergone nasal endoscopic resection of a skull base tumor and repair of CSF rhinorrhea were retrospectively analyzed. The patients were divided into ADM and TF groups according to the difference in repair materials used. We compared and analyzed the intraoperative information and postoperative outcomes. The operation time, blood loss, defect area, and need for blood transfusion were not significantly different between the ALT and TF groups. The postoperative length of hospital stay (14.33 ± 3.66 vs. 16.76 ± 5.51 days; P = 0.669) and the incidence of complications, including wound infection (1 vs. 0; P = 0.270), intracranial infection (1 vs. 1; P = 0.900), hemorrhage (2 vs. 3; P = 0.788), 15-day CSF leak (1 vs. 2; P = 0.658), and respiratory infection (2 vs. 1; P = 0.450) were comparable between the 2 groups. The 6-month (0 vs. 0; P = 1.000) and 12-month (0 vs. 0; P = 1.000) incidence of recurrence also showed no significant differences. The use of the ADM for patients with CSF rhinorrhea showed comparable results in terms of postoperative outcomes compared with the use of TF. ADM could serve as a safe and feasible alternative for endoscopic repair of CSF rhinorrhea after nasal endoscopic resection of skull base tumors. [ABSTRACT FROM AUTHOR]

Abstract: No effective medication for hyperbilirubinemia yet exists. Taurine is believed to exert a neuroprotective action. The aim of the present study was to determine whether taurine protected neurons of the rat anteroventral cochlear nucleus (AVCN) against bilirubin-induced neuronal hyperexcitation. AVCN neurons were isolated from 13 to 15-day-old Sprague–Dawley rats. The effects of bilirubin on the spontaneous excitatory postsynaptic currents (sEPSCs) and action potential currents were compared with those exerted by bilirubin and taurine together. Bilirubin dramatically increased the frequencies of sEPSCs and action potential currents, but not sEPSC amplitude. Taurine suppressed the enhanced frequency of action potentials induced by bilirubin, in a dose-dependent manner. In addition, taurine decreased the amplitude of voltage-dependent calcium channel currents that were enhanced upon addition of bilirubin. We explored the mechanism of the protective effects exerted by taurine using GABAA and glycine receptor antagonists, bicuculline and strychnine, respectively. Addition of bicuculline and strychnine eliminated the protective effects of taurine. Neither bilirubin nor taurine affected the sensitivity of the glutamate receptor. Our findings thus indicate that taurine protected AVCN neurons against bilirubin-induced neuronal hyperexcitation by activating the GABAA and glycine receptors and inhibiting calcium flow through voltage-gated channels. Thus, taurine may be effective in treatment of neonatal hyperbilirubinemia. [Copyright &y& Elsevier]

Abstract: Taurine, one of the most abundant endogenous amino acids in the mammalian central nervous system (CNS), is involved in neural development and many physiological functions. In this study, the interaction between taurine and GABAA/glycine receptors was investigated in young rat (P13–P15) anteroventral cochlear nucleus (AVCN) neurons using the whole-cell patch-clamp method. We found that taurine at low (0.1mM) and high (1mM) concentrations activated both GABAA and glycine receptors, but not AMPA and NMDA receptors. The reversal potentials of taurine-, GABA- or glycine-evoked currents were close to the expected chloride equilibrium potential, indicating that receptors activated by these agonists were mediating chloride conductance. Moreover, our results showed that the currents activated by co-application of GABA and glycine were cross-inhibitive. Sequential application of GABA and glycine or vice versa also reduced the glycine or GABA evoked currents. There was no cross-inhibition when taurine and GABA or taurine and glycine were applied simultaneously, but the response was larger than that evoked by GABA or glycine alone. These results suggest that taurine can serve as a neuromodulator to strengthen GABAergic and glycinergic neurotransmission in the rat AVCN. [Copyright &y& Elsevier]

Abstract: Many mammalian central nervous system neuron responses mediated by GABAA receptors undergo a developmental transition from excitation to inhibition, but little is known about the time of this switch in specific cell types in the developing anteroventral cochlear nucleus (AVCN). In the present study, bushy and stellate cells, two major cell types in the AVCN, were identified according to their morphology and electrophysiology. The equilibrium potential of GABA-evoked currents (E GABA ) was examined using the gramicidin-perforated patch-clamp technique. We found that the action of GABA in bushy and stellate cells switched from predominantly depolarizing to predominantly hyperpolarizing with respect to their resting membrane potential (V rest ) at different postnatal ages. Such a switch in the GABA response of bushy cells occurred before the first postnatal week, whereas that in stellate cells happened at the end of the second postnatal week. Furthermore, we discovered that bushy cells had a more depolarized V rest than did stellate cells before the second postnatal week; however, the E GABA of bushy and stellate cells was not significantly different. Thus, the discrepancy in the timing of the developmental shift from depolarizing to hyperpolarizing GABA responses between bushy and stellate cells may be due to the difference in their V rest , but not due to E GABA itself. These results suggest that GABAergic inhibition functions earlier in bushy than in stellate cells. In contrast, the longer excitatory action of GABA on stellate cells possibly renders them more vulnerable than bushy cells to excitotoxic substances during early development. [Copyright &y& Elsevier]

Abstract: Hyperbilirubinemia is one of the most common clinical phenomena observed in human newborns. To achieve effective therapeutic treatment, numerous studies have been done to determine the molecular mechanisms of bilirubin-induced neuronal excitotoxicity. However, there is no conclusive evidence for the involvement of glutamatergic synaptic transmission in bilirubin-induced neuronal hyperexcitation and excitotoxicity. In the present study, using gramicidin-perforated patch-clamp techniques, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded from lateral superior olive (LSO) neurons isolated from postnatal 11–14-day-old (P11–14) rats. The application of 3μM bilirubin increased the frequency, but not the amplitude, of sEPSCs. The action of bilirubin was tetrodotoxin (TTX)-insensitive, as bilirubin also increased the frequency, but not the amplitude, of mEPSCs. The amplitudes of GABA-activated (I GABA) and glutamate-activated (I glu) currents were not affected by bilirubin. Under current-clamp conditions, no spontaneous action potentials were observed in control solution. However, the application of 3μM bilirubin for 4–6min evoked a considerable rate of action-potential firing. The evoked firing was partially occluded by d,l-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, but completely inhibited by a combination of APV and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), an AMPA receptor antagonist. These results indicate that bilirubin facilitates presynaptic glutamate release, enhances glutamatergic synaptic transmission by activating postsynaptic AMPA and NMDA receptors, and leads to neuronal hyperexcitation. This study provides a better understanding of the mechanism of bilirubin-induced excitotoxicity and determines for the first time that both AMPA and NMDA receptors are likely involved in the excitotoxicity produced by bilirubin. [Copyright &y& Elsevier]

Abstract: Excitotoxicity has been suggested to play an important role in many central nervous system diseases, particularly in bilirubin encephalopathy. Minocycline treatment has been proposed to be one of the most promising potential therapies for excitotoxicity-induced neurological disorders. However, some key questions, such as the electrophysiological effect of minocycline on neuronal excitability and hyperexcitation in pathological conditions, require clarification. In this study, using patch-clamp techniques, we showed that bilirubin increased the frequency of both spontaneous excitatory postsynaptic currents (sEPSCs) and neuronal firing in isolated ventral cochlear nucleus (VCN) neurons at postnatal days 11–14 (P11–14) in rats but it did not affect the amplitude of sEPSCs or glutamate-activated (I Glu) currents. However, minocycline had no effect on sEPSC frequency or I Glu amplitude. Furthermore, minocycline pretreatment did not abolish bilirubin-induced sEPSC potentiation or neuron firing. These data suggest that minocycline does not affect excitatory synaptic transmission or hyperexcitation induced by bilirubin in VCN neurons. From these results, we propose that the neuroprotective efficacy of minocycline, if it can protect neurons against neurotoxicity induced by substances like bilirubin, is mediated by either an alternative mechanism or downstream events post neuronal hyperexcitation. Certainly, additional investigation of the neuroprotective effects of minocycline is required before embarking on further clinical trials. [Copyright &y& Elsevier]

Abstract: Excitotoxicity contributes to bilirubin-induced central nervous system injury; however, the mechanisms involved remain controversial. Previous studies from our lab have demonstrated that in juvenile rats bilirubin faciliates γ-aminobutyric acid (GABA)/glycinergic synaptic transmission through activation of presynaptic protein kinase A (PKA) in isolated neurons of the ventral cochlear nucleus (VCN). However, the descending mechanism and physiological effects of bilirubin-induced potentiation remain unclear. Here, whole-cell recordings show that 3×10−6 M bilirubin increased the frequency of both spontaneous (sPSCs) and miniature (mPSCs) GABA/glycinergic postsynaptic currents in VCN neurons of postnatal day 12–14 (P12–14) rats. This action was dependent on the concentration and duration of exposure to bilirubin and was only partially suppressed by 10−5 M bicuculline. The potentiation effect on mPSCs persisted in a Ca2+-free solution, but was fully occluded by pretreatment with 1,2 bis-(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), an intracellular Ca2+ chelator. Following pretreatment of the neurons with BAPTA-AM, forskolin, a PKA activator, had no effect on the frequency or amplitude of mPSCs. This suggests that Ca2+ release from presynaptic stores is part of the descending pathway of PKA activation and is responsible for biliurbin-induced potentiation of cell activity. Using gramicidin-perforated patch recordings, the reversal potential of GABA-evoked currents (EGABA) was also investigated. The GABA response resulted in depolarization of 12 of 20 recorded VCN neurons from P12–14 rats. Therefore, potentiation of depolarizing GABA/glycinergic transmission by bilirubin may underlie bilirubin excitotoxicity, which may play a role in the hearing impairment observed among hyperbilirubinemic neonates. [Copyright &y& Elsevier]

Abstract: Previous studies have suggested that bilirubin can potentiate GABA/glycinergic synaptic transmission in lateral superior olivary nucleus neurons, but the cellular mechanism has not been defined. The present study evaluated the possible roles of protein kinase A (PKA) and C (PKC) in bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus (VCN) neurons. VCN neurons were acutely isolated from postnatal 10-12-day-old (P10-12) rats and were voltage-clamped in whole-cell mode. Miniature inhibitory postsynaptic currents (mIPSC) frequencies, but not amplitude, were increased by bilirubin. Forskolin (PKA activator) and H-89 (PKA inhibitor) also individually increased mIPSCs frequency, with an additional increase induced by co-incubation with bilirubin and H-89. Pretreatment with forskolin blocked bilirubin potentiation. mIPSC frequency was not altered by phorbol 12,13-diacetate (PKC activator), but mIPSC frequency was increased following co-application of bilirubin. The mIPSC frequency was increased by chelerythrine (PKC inhibitor), and then further increased after the addition of bilirubin. Neither H-89, forskolin, nor PDA, nor their co-application with bilirubin affected mIPSC amplitudes of GABA-activated (IGABA)/glycine-activated (Igly) currents, suggesting a presynaptic locus of activity. Chelerythrine decreased the mIPSC amplitudes and IGABA/Igly, suggesting a postsynaptic locus of activity. These data suggest that both PKA and PKC can modulate GABA and glycine release in rat VCN neurons. Bilirubin facilitates transmitter release via presynaptic PKA activation, which might provide insight into the cellular mechanism underlying bilirubin-induced hearing dysfunction. [ABSTRACT FROM AUTHOR]