Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.

Electroacupuncture ameliorate learning and memory by improving N -acetylaspartate and glutamate metabolism in APP/PS1 mice

OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.

Protective effect of tetrahydroxystilbene glucoside on hippocampal neurons damage induced by glutamate in rats / 中国康复理论与实践

@#ObjectiveTo observe the protective effect of tetrahydroxystilbene glucoside (TSG) on rats' hippocampal neuronal damage induced by glutamate (Glu) in the culture.MethodsHippocampus was isolated from newborn SD rats and dispersedly cultured in the medium for 9 days. Neurons were incubated with TSG (5—100μmol/L) for 24h, the cells were washed twice with Lock's solution without Mg2+,then Glu 500 μmol/L was added. Thirty min later, the reaction was terminated by washing the monolayer cells twice with the Lock's solution and then cultures were kept at 37℃ for 24h. Cell viability was measured by MTT method and cell membrane damage was determined by LDH leakage; with Fluo-3/AM as an intracellular calcium indicator and added into the bathing medium, fluorescent intensity of intracellular free calcium were observed through laser scanning confocal microscopy (LSCM).ResultsAfter the treatment with 5—100μmol/L TSG for 24h, the decrease of cell viability and the increase of LDH leakage caused by Glu was obviously resisted dose dependently. TSG inhibited increase of Ca2+ in cytoplasm, compared with model group.ConclusionTSG can significantly promote the cell viability and reduce the cell membrane damage in Glu treating hippocampal neurons. The neuroprotective activities of TGS is mediated by inhibiting Ca2+ overload in cytoplasm.

Relation between modulation of the N-methyl-D-aspartate receptor and cyanide-induced neurotoxicity / 中国临床药理学与治疗学

Cyanide can activate the N-methyl-D-aspartate (NMDA) receptor by two approaches directly and indirectly. Firstly cyanide-induced depletion of energy is associated with the activation of NMDA receptors indirectly by increasing extracellular glutamate (Glu) and affecting cytosolic Ca 2+ homeostatic mechanisms. Secondly most likely as a conditioner of the NMDA receptor, cyanide enhances NMDA receptors responses by modulating redox sites of cysteine residue located in the subunit NR 1 or NR 2 of the NMDA receptor. NMDA receptor-induced neurotoxicity, initiated by the direct or indirect activation of NMDA receptor, leads to neuronal injury, apoptosis or necrosis finally. Therefore, it is believed that the activation of the NMDA receptor is presumably the key event in the mechanism of cyanide-induced neuronal injures.

Neuroprotective effect of sodium oxybate against focal cerebral ischemia-reperfusion injury and the relation to GABA in rats / 中国药理学通报

AIMTo study the protective effect of sodium oxybate (SO) against focal cerebral ischemia-reperfusion injury in rats, and the relationship between the effects of SO and ?-aminobutyric acid (GABA). METHODSThe reversible middle cerebral artery occlusion (MCAO)model in rats was established to investigate the role of SO. The scores of neurological deficits was detected by Longa EZ method in MCAO rats. The extracellular levels of glutamate (Glu) and GABA in CSF were measured by high performance liquid chromatography-fluorometer (HPLC-FR) method, and the weight of cerebral infraction was detected. RESULTSThe scores of neurological deficits and the weight of cerebral infraction markedly decreased by SO while the ratio of GABA/Glu obviously increased administered SO in MCAO rats. CONCLUSIONSSO could prevent MCAO rats from ischemia-reperfusion injury, the protective effect is related to SO keeping dynamic balance of excition-inhibition, and persisting inhibition-depended effect.