ABSTRACT
Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
ABSTRACT
Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
Subject(s)
Animals , Rats , Aconitine/pharmacology , Analgesics/pharmacology , Pharmaceutical Preparations , Rats, Sprague-DawleyABSTRACT
Understanding the effects of radiation and its possible influence on the nervous system are of great clinical interest. However, there have been few electrophysiological studies on brain activity after exposure to ionizing radiation (IR). A new methodological approach regarding the assessment of the possible effects of IR on brain activity is the use of linear and nonlinear mathematical methods in the analysis of complex time series, such as brain oscillations measured using the electrocorticogram (ECoG). The objective of this study was to use linear and nonlinear mathematical methods as biomarkers of gamma radiation regarding cortical electrical activity. Adult Wistar rats were divided into 3 groups: 1 control and 2 irradiated groups, evaluated at 24 h (IR24) and 90 days (IR90) after exposure to 18 Gy of gamma radiation from a cobalt-60 radiotherapy source. The ECoG was analyzed using power spectrum methods for the calculation of the power of delta, theta, alpha and beta rhythms and by means of the α-exponent of the detrended fluctuation analysis (DFA). Using both mathematical methods it was possible to identify changes in the ECoG, and to identify significant changes in the pattern of the recording at 24 h after irradiation. Some of these changes were persistent at 90 days after exposure to IR. In particular, the theta wave using the two methods showed higher sensitivity than other waves, suggesting that it is a possible biomarker of exposure to IR.
Subject(s)
Animals , Male , Cerebral Cortex/radiation effects , Electrocorticography/methods , Gamma Rays/adverse effects , Radiation, Ionizing , Radiation Injuries/diagnosis , Biomarkers , Brain/radiation effects , Linear Models , Nonlinear Dynamics , Rats, Wistar , Statistics, Nonparametric , TimeABSTRACT
Objective The current study was aimed to establish an electrically amygdala kindling model of refractory epilepsy in Sprague-Dawley rats, and to study their changes of electrocorticagram ( ECoG ) .Materials and methods Male Sprague-Dawley rats were used in the experiment.Two-polar electrode was implanted into the right amygdala stereotactically.Two weeks after the surgery, electrical stimulations were given to elicit the grade 4 seizure in all animals with the fast kindling protocol.Rekindling was administrated after the first kindling.The after discharge threshold ( ADT) and the number of stimulus were reassessed in the two kindling protocols.ECoG and the behavior of the animals were recorded during the whole experiment.Result The changes of ECoG and behavior: Animals showed stage 1 -3 seizure when the ADT was assessed.While during the kindling period, the animals showed generalized convulsion with stage 4-5 seizure.ECoG showed sharp waves, spike waves, sharp-slow waves and spike-slow waves.Statistical analysis showed that the ADT was not significantly increased at two weeks after kindling ( from 83.33 ±22.29μA to 84.17 ±16.76μA, P=0.923 ) .The number of stimulus given to elicit the stage 4 convulsion was not significantly increased as well ( from 4.41 ±2.27 to 5.58 ±3.96, P=0.231 ) .Conclusions Rapid kindling model of epilepsy in rats is an effective epilepsy model, which is stable for 2 weeks.
ABSTRACT
Objective To explore the effect of liensinine on cortical EEG of epileptic rats induced by lithium chloride-pilocarpine,and investigate the effective spectrum of liensinine on epilepsy.Methods 32 SD rats were randomly divided into four groups:low dose of liensinine group(2.5 mg/mL, 10μL),high dose of liensinine group(5 mg/mL,10μL),the normal saline group(10μL)which was negative control group,levetiracetam group (100 mg/mL,10μL)which was positive control group,8 rats in each group.Electrocorticogram of rats was recorded after chloride lithium-pilocarpine model was induced.The anesthetic rats were fixed on stereotaxic apparatus after the epilepsy model was confirmed by ethology.A trochar was put into the left lateral ventricle.Rats were implanted with epidural recording electrodes.After the cortical EEG was recorded about 30 minutes, liensinine (at concentration of 2.5,5 mg/mL),levetiracetam and 0.9% sodium chloride was injected into lateral ventricle.Electrocorticogram was recorded about 150 minutes again.The frequency of epileptic discharge was observed every 30 minutes.The differences of frequency in the same group and the different change of frequency between groups at the same period were compared.Results The frequency of epileptic discharge decreased in low dose of liensinine group,high dose of liensinine group and levetiracetam group after administration ,there was significantly statistical difference in low dose of liensinine group after administration about 60 minutes(P<0.01 ),there was significant statistics difference in high dose of liensinine group after administration about 30 minutes(P<0.01),and the same change in levetiracetam group within 30 minutes after administration(P<0.01);the change of frequency of epileptic discharge was no significantly statistical difference between pro-and post-administration in the normal saline control group.The difference of the frequency change in epileptic discharge at the same period between liensinine group and levetiracetam group was observed ,there was statistic difference between low dose of liensinine group and levetiracetam group at the period of thirty to sixty minutes after administration,there was no statistic difference at other periods;there was no statistic difference between high dose of liensinine group and levetiracetam group at every period.Conclusion Liensinine could inhibit the epileptic discharges in acute model of epileptic rats induced by chloride lithium-pilocarpine.
ABSTRACT
Objective To explore the surgical treatment of posttraumatic epilepsy in functional cerebral area Methods After preoperative evaluation,nineteen patients with intractable posttraumatic epilepsy of functional cerebral area underwent multiple subpial transaction under the electrocorticogram monitoring during the operation, combining with anterior corpus callosotomy, anterior temporal lobectomy and selective amygdalo-hippocampectomy. Results The follow-up results showed seizures of these patients improved considerably. According to Engel' s grading,among 19 cases,10 cases were grade Ⅰ ,7 cases were grade Ⅱ ,2 cases were grade Ⅲ ,and no cases were grade Ⅳ. Conclusions The satisfactory clinical outcome of the surgical treatment of intractable posttraumatic epilepsy in functional cerebral area could be obtained with the help of careful preoperative evaluation and multiple subpial transaction under the electrocorticogram monitoring.
ABSTRACT
A tumor and cortical dysplasia may be the concomitant cause of the causes of intractable epilepsy, but a few studies have examined so far. From among 249 patients who underwent surgery for intractable epilepsy at Dongsan Epilepsy Center, those in whom neoplasia and cortical dysplasia coexisted were selected for this study, and were reviewed the clinical, electrophysiological, neuroimaging and pathological findings. In 17 of 25 lesionrelated epilepsy patients, tumors including dysembryoplastic neuroepithelial tumor(DNT)(n=6), ganglioglioma(n=5), gangliocytoma(n=1), low grade astrocytoma(n=2), oligodendroglioma(n=2), hypothalamic hamartoma(n=1) were verified. Of these 17 cases involving tumors, concomitant cortical dysplasia was observed in 7(DNT; 6, ganglioglioma; 1). All these patients underwent sophisticated presurgical evaluation and intraoperative acute recording(EcoG) for the identification of adjacent or remote epileptogenic areas as well as functional brain mapping by electrical stimulation or SSEP to verify the eloquent areas. In intractable epilepsy, the coexistence of cortical dysplasia and neoplasia is not common, though careful intraoperative evaluation of the tumor and surrounding tissue using electrocorticogram (EcoG) may lead to its pathological identification and excellent surgical results for these rare lesions.