Temporal lobe epilepsy(TLE) is a common type of epilepsy and is not well controlled by current treatments.The frequent failure to treat TLE may be due to our lack of precise cellular/circuit mechanisms underlying TLE....Temporal lobe epilepsy(TLE) is a common type of epilepsy and is not well controlled by current treatments.The frequent failure to treat TLE may be due to our lack of precise cellular/circuit mechanisms underlying TLE.The early series of our studies have proved the success of low-frequency stimulation treatment for epilepsy,which was mainly depending on the stimulation target,the stimulation frequency and stimulation time(the therapeutic-window phenomenon).Now,by using optogenetics,viral tracing,multiple-channel EEG analysis,imaging,electrophysiology and pharmacology strategies,we are continued to investigate the circuit mechanism of therapeutic deep brain stimulation,and found that entorhinal principal neurons mediate antiepileptic ″ glutamatergic-GABAergic″ neuronal circuit for brain stimulation treatments of epilepsy.Meanwhile,we are currently focusing on the interplay of inhibitory and excitatory network in the key input/output regions of the hippocampus that related to the generation of in TLE.Specially,we found that depolarized GABAergic signaling in subicular microcircuit mediates generalized seizures in TLE and a direct septal cholinergic circuit attenuates TLE through driving hippocampal somatostatin inhibition.These findings may be of therapeutic interest in understanding the pathological neuronal circuitry in TLE and further the development of novel therapeutic approaches or drug targets.展开更多
AIM:Vincristine is one of the most commonly used chemotherapeutic drugs to treat a variety of malignant diseases,including leukemia and lymphoma.Studies have shown that vincristine cause painful effects,whereas Salvia...AIM:Vincristine is one of the most commonly used chemotherapeutic drugs to treat a variety of malignant diseases,including leukemia and lymphoma.Studies have shown that vincristine cause painful effects,whereas Salvia officinalis(SO) showed analgesic and anti-inflammatory effects.The aim of this study is to investigate the effects of the SO hydro-alcoholic extract on vincristine-induced peripheral neuropathy in mice in comparison with morphine.METHODS:Experiments were performed on 60 NMRI male mice weighing 25-30 g divided into six groups.The individual groups received normal saline,SO hydro-alcoholic extract,vincristine,SO hydro-alcoholic extract and vincristine(12 days before formalin test),morphine,and vincristine and morphine,respectively.The injected hind paw biting and licking was measured in a 5-minute interval for one hour.RESULTS:The results showed that formalin induce significant(P < 0.05) pain responses(the first phase:0-5 min and the second phase:15-40 min after injection).Administration of SO extract before formalin test showed significant(P < 0.05) decrease of pain response in the second phase.Administration of vincristine caused significant(P < 0.05) increase in the second phase of pain response.Injections of SO extract and vincristine showed that SO significantly(P < 0.05) decrease the second phase of vincristine-induced pain.Morphine decreased vincristine-induced pain in the first and second phase of formalin test significantly(P < 0.05).In comparison,morphine showed analgesic effects in the first phase and SO extract showed significant(P < 0.05) anti-inflammatory effects in the second phase of formalin test.CONCLUSION:Both SO and vincristine showed analgesic and painful neuropathic effects,suggesting that SO extract could be useful in the treatment of vincristine-induced peripheral neuropathic pain.展开更多
基金National Natural Science Foundation of China(913322028122100381603084).
文摘Temporal lobe epilepsy(TLE) is a common type of epilepsy and is not well controlled by current treatments.The frequent failure to treat TLE may be due to our lack of precise cellular/circuit mechanisms underlying TLE.The early series of our studies have proved the success of low-frequency stimulation treatment for epilepsy,which was mainly depending on the stimulation target,the stimulation frequency and stimulation time(the therapeutic-window phenomenon).Now,by using optogenetics,viral tracing,multiple-channel EEG analysis,imaging,electrophysiology and pharmacology strategies,we are continued to investigate the circuit mechanism of therapeutic deep brain stimulation,and found that entorhinal principal neurons mediate antiepileptic ″ glutamatergic-GABAergic″ neuronal circuit for brain stimulation treatments of epilepsy.Meanwhile,we are currently focusing on the interplay of inhibitory and excitatory network in the key input/output regions of the hippocampus that related to the generation of in TLE.Specially,we found that depolarized GABAergic signaling in subicular microcircuit mediates generalized seizures in TLE and a direct septal cholinergic circuit attenuates TLE through driving hippocampal somatostatin inhibition.These findings may be of therapeutic interest in understanding the pathological neuronal circuitry in TLE and further the development of novel therapeutic approaches or drug targets.
文摘AIM:Vincristine is one of the most commonly used chemotherapeutic drugs to treat a variety of malignant diseases,including leukemia and lymphoma.Studies have shown that vincristine cause painful effects,whereas Salvia officinalis(SO) showed analgesic and anti-inflammatory effects.The aim of this study is to investigate the effects of the SO hydro-alcoholic extract on vincristine-induced peripheral neuropathy in mice in comparison with morphine.METHODS:Experiments were performed on 60 NMRI male mice weighing 25-30 g divided into six groups.The individual groups received normal saline,SO hydro-alcoholic extract,vincristine,SO hydro-alcoholic extract and vincristine(12 days before formalin test),morphine,and vincristine and morphine,respectively.The injected hind paw biting and licking was measured in a 5-minute interval for one hour.RESULTS:The results showed that formalin induce significant(P < 0.05) pain responses(the first phase:0-5 min and the second phase:15-40 min after injection).Administration of SO extract before formalin test showed significant(P < 0.05) decrease of pain response in the second phase.Administration of vincristine caused significant(P < 0.05) increase in the second phase of pain response.Injections of SO extract and vincristine showed that SO significantly(P < 0.05) decrease the second phase of vincristine-induced pain.Morphine decreased vincristine-induced pain in the first and second phase of formalin test significantly(P < 0.05).In comparison,morphine showed analgesic effects in the first phase and SO extract showed significant(P < 0.05) anti-inflammatory effects in the second phase of formalin test.CONCLUSION:Both SO and vincristine showed analgesic and painful neuropathic effects,suggesting that SO extract could be useful in the treatment of vincristine-induced peripheral neuropathic pain.
