BACKGROUND: Methylmercury (MeHg) causes damage specifically in cerebrocortical neurons, but not in hippocampal neurons. In our previous studies using cultured neurons, we found that brain-derived neurotrophic factor (BDNF), which is prominently present in hippocampal neurons, plays a key role in resistance to MeHg neurotoxicity. Our findings, combined with recent findings that moderate exercise increases BDNF in the brain, led us to hypothesize that moderate exercise protects against MeHg-induced neurotoxicity by inducing BDNF expression. METHODS: C57 black 6NJcl (C57BL/6NJcl) male mice were used to evaluate the effects of treadmill exercise (a moderate exercise) on the neurotoxicity of MeHg exposure at 1.5 mg/kg/day. The effects of treadmill exercise on MeHg neurotoxicity were evaluated through neurobehavioral, neuropathological, and biochemical analyses using brain tissue, blood, and muscle tissue. RESULTS: Treadmill exercise had a significant inhibitory effect on the neurological symptoms associated with apoptotic neuronal death and subsequent cerebrocortical neuron loss induced by MeHg exposure. In the cerebral cortex, treadmill exercise significantly increased BDNF levels and activated the neuroprotective-related BDNF-tropomyosin receptor kinase (Trk) B and p44/42 mitogen-activated protein kinase (MAPK) pathways along with significantly suppressing the neuronal cell death-associated p38 MAPK pathway. Furthermore, treadmill exercise significantly increased fibronectin type III domain containing 5 (FNDC5) expression in the muscle tissue and elevated ed the concentration of its metabolite, irisin, in the blood. CONCLUSIONS These results suggest that treadmill exercise increases BDNF in the brain and suppresses neurotoxic pathways, ultimately protecting against MeHg neurotoxicity. Moreover, the increase of BDNF in the brain may be attributed to the exercise-induced increased expression of FNDC5 in muscle tissue from where it is released into the blood as irisin and finally transferred into the brain and promoted BDNF production.
Animals ; Brain-Derived Neurotrophic Factor/genetics* ; Methylmercury Compounds/toxicity* ; Male ; Mice ; Mice, Inbred C57BL ; Physical Conditioning, Animal ; Brain/drug effects* ; Neurotoxicity Syndromes/prevention & control*

The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.
Animals ; Humans ; Anesthetics, Intravenous/adverse effects* ; Neuroprotective Agents/pharmacology* ; Propofol ; Neurotoxicity Syndromes/prevention & control* ; Central Nervous System/drug effects* ; Dexmedetomidine

OBJECTIVETo assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin.

METHODSThis is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups.

RESULTSNinety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar.

CONCLUSIONThis study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.

Adolescent ; Adult ; Aged ; Anticonvulsants ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Calcium Gluconate ; administration & dosage ; Colorectal Neoplasms ; drug therapy ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Glutathione ; therapeutic use ; Humans ; Infusions, Intravenous ; Leucovorin ; adverse effects ; therapeutic use ; Magnesium Sulfate ; administration & dosage ; Male ; Middle Aged ; Neurotoxicity Syndromes ; etiology ; prevention & control ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Stomach Neoplasms ; drug therapy ; Young Adult

OBJECTIVETo investigate the mechanisms of taurine (Tau) preventive effect on neurotoxicity induced by manganese (Mn) in rat's prefrontal cortex.

METHODSSD rats were divided into four groups after one week of observation: normal control:the group animals received daily intraperitoneal (ip.) injections of sterile saline for 3 months; Mn treated group (Mn): rats received ip. injection of MnCl(2).4H(2)O once a day for 3 months; Tau preventive group (Mn + Tau): The Mn level of this group were the same as Mn's, the Tau level 200 mg/kg, three times per week, for 3 months; Tau treated group (Mn-->Tau): After received the daily injection of Mn as Mn group for 3 months, the rats received Tau three times per week for 3 months. The dose of Mn and Tau were the same as above. The experiment lasted 6 months.

RESULTS(1) Mn induced apoptosis of neurons in rat's prefrontal cortex. The ratio of apoptosis of neurons in the Mn treated group [(20.0 +/- 4.3)%] was higher than that of the control group [(1.8 +/- 2.1)%] (P < 0.05) and the ratio of apoptosis in Tau preventive group (Mn + Tau) was lower than that of the Mn treated group (P < 0.05). (2) The production of MDA in Mn treated group was higher than the control group (P < 0.05) and the activity of SOD was lower than that in the control group. In Tau preventive group (Mn + Tau), Tau increased the activity of SOD and decreased the production of the MDA, with the significant difference level compared to the Mn treated group (P < 0.05).

CONCLUSIONMn induces apoptosis in rat's prefrontal cortex neurons. The main mechanisms of Tau preventing cytotoxicity against Mn is the reduction of the oxidative stress in prefrontal cortex neurons.

Animals ; Apoptosis ; drug effects ; Drug Antagonism ; Male ; Manganese ; toxicity ; Neurons ; drug effects ; metabolism ; pathology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; prevention & control ; Prefrontal Cortex ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Taurine ; pharmacology

OBJECTIVETo investigate the neuroprotective effect of estradiol on the release of excitatory amino acid (EAAs) mediator, and the activity of ATPase in cerebro-cortical synaptosome membrane of rats exposed to deltamethrin.

METHODSUsing HPLC to detect EAAs release, and colorimeter method to measure the activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase in the cerebro-cortical synaptosomes of ovariectomized rats exposed to deltamethrin (2 x 10(-5)mol/L), and treated with different doses of 17beta estradiol (10(-5), 10(-8), 10(-11) mol/L). Meanwhile, the estrogen receptor (ER) antagonist, tamoxifen, was used to investigate the effect on estradiol.

RESULTSThe release of Asp and Glu from the cerebro-cortical synaptosomes was significantly increased by 2 x 10(-5)mol/L deltamethrin exposure at the depolarizing state evoked by 50 mmol/L KCl, while 10(-8), 10(-11) mol/L 17beta estradiol could partly inhibit the effect of deltamethrin on the release of Asp (28.42%, 24.36%, respectively), Glu (21.52%, 14.57%, respectively). The activities of 4 kinds of ATPase were inhibited by 2 x 10(-4) mol/L deltamethrin, and these effects could be blocked by 10(-5) mol/L estradiol, while the activity of Ca(2+)-ATPase was increased by 10(-8), 10(-11) mol/L of estradiol. However, no obvious antagonistic effect of tamoxifen on the function of estradial on EAAs release or the activities of ATPase was found.

CONCLUSIONEstradiol showed certain neuroprotective effect on the release of EAAs and the inhibition on ATPase induced by deltamethrin. The effect of estradiol on synaptosomes may indicate the nongenetic mechanism of estradiol.

Animals ; Aspartic Acid ; secretion ; Cerebral Cortex ; drug effects ; metabolism ; Estradiol ; pharmacology ; Glutamic Acid ; secretion ; Insecticides ; toxicity ; Neurotoxicity Syndromes ; prevention & control ; Nitriles ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar ; Synaptosomes ; drug effects ; metabolism