OBJECTIVETo observe cerebral protective effect of muscone (nasal administration) on traumatic brain injury model rats.

METHODSSD rats were divided into the sham-operation group, the model group, and the treatment groups according to random digit table, 50 in each group. Traumatic brain injury model was established by controlled cortical strike. Rats in the sham-operation group received surgery and anesthesia procedures only, with no strike. Muscone (1.8 mg/kg) was delivered to rats in the treatment group using in situ nasal perfusion, 30 min each time, twice daily for 7 successive days. Water content of brain tissue was detected in each group before intervention (T1), at day 3 of intervention (T2), day 5 of intervention (T3), and after intervention (T4), respectively. Expression levels of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detected using immunohistochemical analysis.

RESULTSCompared with the sham-operated group, water content of brain tissue increased (P < 0.05), and expression levels of NGF and BDNF decreased in the model group at T1, T2, T3, and T4 (P <0. 01). Compared with the model group, water content of brain tissue decreased (P < 0.05), and expression levels of NGF and BDNF increased (P < 0.01) in the treatment group at T1, T2, and T3.

CONCLUSIONNasal administration of muscone could reduce water content of brain tissue, alleviate cerebral edema, promote secretion of BDNF and NGF by olfactory ensheathing cells in traumatic brain injury rats.

Animals ; Brain ; drug effects ; Brain Injuries ; drug therapy ; Brain-Derived Neurotrophic Factor ; metabolism ; Cycloparaffins ; pharmacology ; Nerve Growth Factor ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of a Gold Belt (GB, a traditional Chinese herbal medicine) combined with methyl-prednisolone (MP) on the motor function and brain-derived neurotrophic factor (BDNF) expression in rats with contusive spinal cord injury (SCI).

METHODSThirty adult female SD rats were randomly divided into 5 equal groups, namely the sham-operated group, SCI group, SCI with MP treatment group (MP group, with intramuscular injection of 50 mg/kg MP within 8 hours after SCI and then dosage reduced 10 mg/kg daily), SCI with GB treatment group (GB group, with intragastric gavage of GB 50 mg/kg once daily for 7 days), and combined GB and MP treatment group. The Basso, Beattie and Bresnahan (BBB) locomotor scale was used to evaluate the hindlimb motor function of the rats on days 1, 3, 7, 14, 21 and 28 after the injury. After the last evaluation the rats were sacrificed for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of spinal cord.

RESULTSBDNF were distributed mainly in neurons in the spinal cord grey matter ventral horn and dorsal horn of the rats. The number of BDNF-positive neurons and BBB scores in the combined treatment group were significantly higher than those in the other 4 groups (P<0.05).

CONCLUSIONGB combined with MP produces better therapeutic effects for treating SCI than GB or MP used alone, and such effects are probably related with enhanced BDNF expression in the spinal cord.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Methylprednisolone ; pharmacology ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; metabolism

OBJECTIVETo observe the effects of Shuyu Ningxin Recipe (SNR) on the praxiology and the expressions of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) of model rats with chronic stress-induced depression, thus exploring its anti-depression mechanisms.

METHODSSixty adult SD rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the fluoxetine group, the high dose SNR group, the medium dose SNR group, and the low dose SNR group, 10 in each group. All rats were subjected to establish chronic stress-induced depression model for 21 consecutive days. Except those in the normal control group, rats in the rest groups received gastrogavage from the 22nd day. Mice in the model group were administered with normal saline by gastrogavage. SNR at 25.0, 7.5, and 2.5 g/kg was respectively administered to rats in the high dose SNR group, the medium dose SNR group, and the low dose SNR group by gastrogavage. Fluoxetine suspension (12 mg/kg) was given to rats in the fluoxetine group by gastro-gavage. All medication lasted for 3 successive weeks. The weight, open-field test, and the immobility time in forced swimming test were determined before modeling, 3 weeks (after successful modeling), and 6 weeks (by the end of medication). The expressions of hippocampal BDNF and TrkB were measured after the brain tissues were drawn by the end of the experiment.

RESULTSCompared with the normal control group, the body weight grew slowly, the behavior index decreased, the immobility time in forced swimming test was prolonged, and the expressions of BDNF and TrkB were weaken in the model group (P <0.05, P <0.01).The body weight increased, the behavior was improved, the immobility time in forced swimming test was shortened, and the expressions of BDNF and TrkB were enhanced in the high dose SNR group and the fluoxetine group by the and of medication, showing statistical difference when compared with the model group (P <0.05, P <0.01).

CONCLUSIONSNR could exert anti-depression by improving the expression levels of hippocampal BDNF and TrkB.

Animals ; Behavior, Animal ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; metabolism ; Stress, Psychological ; metabolism

OBJECTIVETo explore the mechanism of brain-derived neurotrophic factor (BDNF) promoting human multiple myeloma (MM) cells secreting matrix metalloproteinase-9 ( MMP-9).

METHODSGelatin zymography of culture supernatants was performed to visualize the content of MMPs in myeloma RPMI 8226 cells stimulated by BDNF. NF-kappaB activity was determined by chemiluminescent electrophoretic mobility shift assay (EMSA).

RESULTSTreatment with 25, 50, 100 and 200 microg/L BDNF for 24 h significantly (P < 0.01) enhanced the level of MMP-9 (2.03+/-0.48, 2.99+/-0.046, 4.63+/-0.62 and 5.62+/-1.29 microg/L, respectively, vs 1.00 microg/L of the control) secreted by RPMI8226 cells in a dose-dependent manner, while that of MMP-2 was not changed significantly (P > 0.05). The BDNF-induced activation of MMP-9 was inhibited by pretreatment with pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, or K252 alpha, a specific tyrosine inhibitor of TrkB which is the receptor for BDNF. Pretreated with 1 mmol/L PDTC or 500 nmol/L K252 alpha significantly downregulated MMP-9 secreted by the 100 microg/L of BDNF stimulated RPMI 8226 cells (the optical density values were 867.52+/-101.81 and 727.98 +/-92.05, respectively, vs 1,159.01+/-233.15 of the control). The activity of NF-kappaB was enhanced by BDNF in a dose-dependent manner, and pretreatment with K252 alpha could significantly inhibit this activation at 1, 6, 12 and 24 h (P < 0.05) in a time-dependent manner.

CONCLUSIONBDNF plays an important role in the angiogenesis of MM to promote the up-regulation of MMP-9, which may be induced by enhanced NF-kappaB activity in MM cells.

Brain-Derived Neurotrophic Factor ; pharmacology ; Cell Line, Tumor ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Multiple Myeloma ; metabolism ; NF-kappa B ; metabolism

BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. METHODS: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. RESULTS: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. CONCLUSIONS A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Humans ; Mice ; Animals ; Psilocybin/metabolism* ; Fear ; Extinction, Psychological ; Brain-Derived Neurotrophic Factor/metabolism* ; Bromodeoxyuridine/pharmacology* ; Hippocampus/metabolism* ; Neuronal Plasticity ; TOR Serine-Threonine Kinases/metabolism*

OBJECTIVETo study the expression of brain-derived neurotrophic factor (BDNF) gene modified bone marrow mesenchymal stem cells (MSC) in the cochlea of drug-deafened guinea pigs and its protection to spiral ganglion cells (SGC).

METHODSGuinea pigs deafened by subcutaneous injection of amikacin were randomly divided into two groups, BDNF gene modified bone marrow MSC were injected into the cochlea through fenestration of scala tympani in the experimental group, while artificial perilymphatic fluid were injected in the control group. Experimental animals were executed at 7 and 28 days post-operation. Expression of BDNF mRNA was examined by quantitate real time RT-PCR, histological images of cochlear sections were analyzed to calculate the cellular density of the SGC, and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was used to identify the apoptotic neurons.

RESULTSThe BDNF expressive level in experimental group was higher than in the control group at 7 d and 28 d post-operation, whose differences were both statistically significant (P < 0.01). And, It showed a higher abundance of ganglion cell numbers, as well as a decreased apoptotic index in experimental group compared with the control group at 7 d and 28 d post-operation, whose differences were all statistically significant (P < 0.01).

CONCLUSIONBDNF gene modified MSC could maintain expression for at least 28 days after transplantation into cochlea of drug deafened guinea pigs, and protect SGC.

Animals ; Bone Marrow Cells ; metabolism ; Brain-Derived Neurotrophic Factor ; genetics ; pharmacology ; Deafness ; chemically induced ; therapy ; Guinea Pigs ; Mesenchymal Stromal Cells ; metabolism ; Organisms, Genetically Modified ; Spiral Ganglion ; drug effects

OBJECTIVETo observe the evolutionary tendency of brain derived neurotrophic factor (BDNF) of the limbic system in post-stroke model rats and the intervention effect of Yinao Jieyu Recipe (YJR).

METHODSMale Wistar rats were randomly divided into the normal control group (n =6), the sham-operation group (n =7), the multiple cerebral infarction (MCI) group (n =10), the post-stroke depression (PSD) group (n =10), the Chinese medicine (CM) treatment group (n =10), and the Western medicine (WM) treatment group (n =10) according to random digit table after open-field testing. Rats in the normal control group were routinely fed. 0. 3 mL normal saline was intravenously pushing from the external carotid artery to rats in the sham-operation group, and distilled water administered to them by gastrogavage. Each dose allogenic microthrombi were in vitro pushed to rats in the rest groups from the external carotid artery. The PSD model was duplicated by 21-day chronic unpredictable mild stress (CUMS) and single cage feeding in the PSD group 7 days after surgery. After preparing models rats in the CM group and the WM group were administered with YJR and Nimodipine respectively for 4 successive weeks. Changes of BDNF and the intervention effect of YJR were observed at week 1, 2, and 4 after intervention.

RESULTSImmunohistochemical results of BDNF showed, compared with the normal control group, expression levels of BDNF in the hippocampus, hypothalamus, and amygdala decreased in the MCI group at week 2 and 4 (P <0. 01 , P <0. 05) ; expression levels of BDNF in each part decreased in the PSD group at week 1-4 (P <0.01). Compared with the MCI group, expression levels of BDNF in each part decreased in the PSD group at week 1-4 (P <0. 01). Compared with the PSD group, expression levels of BDNF in each part increased in the CM group at week 1-4 (P <0. 01).

CONCLUSIONBDNF changes existed in post-stroke model rats, and YJR could slow down this progress.

Amygdala ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; Depressive Disorder ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; Male ; Models, Animal ; Rats ; Rats, Wistar ; Stroke ; drug therapy

OBJECTIVETo explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.

METHODSForty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.

RESULTSSignificant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.

CONCLUSIONTreatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.

Aging ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; CA1 Region, Hippocampal ; metabolism ; CA3 Region, Hippocampal ; metabolism ; Dentate Gyrus ; metabolism ; Erythropoietin ; pharmacology ; Frontal Lobe ; metabolism ; Galactose ; Humans ; Male ; Neurons ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology

OBJECTIVETo explore the effect of Buyang Huanwu Decoction (BYHWD) and its disassembled recipes on rats' neurogenesis after focal cerebral ischemia and to investigate its underlying molecular mechanisms.

METHODSFocal cerebral ischemia model was induced by occlusion of the right middle cerebral artery for 90 min using the intraluminal filament model. Rats were divided into the sham-operation group, the model group, the BYHWD group, the qi supplementing group, and the blood activating group. Medication was performed by gastrogavage 24 h after ischemia for 14 successive days. 5-bromodeoxyuridine (BrdU) (at 50 mg/kg) was intraperitoneally injected, once per day for 14 successive days. The neurological function was assessed using modified neurological severity score (mNSS) and the corner test at day 1, 7, and 14 after ischemia. BrdU/Nestin, BrdU/NeuN, and BrdU/GFAP positive cells were examined by double immunofluorescence at day 14 after ischemia. The protein expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were detected by Western blot at day 14 after ischemia.

RESULTSCompared with the model group, the score of mNSS and the frequency of turning right significantly decreased in the BYHWD group and the qi supplementing group (P < 0.01), the number of BrdU/Nestin in the subventricular zone of the lateral ventricle, and BrdU/ NeuN and BrdU/GFAP positive cells in the peripheral ischemic cortex increased (P < 0.05, P < 0.01), protein expression of BDNF and VEGF increased (P < 0.05, P < 0.01). In the qi supplementing group, there was no statistical difference in BrdU/GFAP. But there was no statistical difference in each index of the blood activating group (P > 0.05). Compared with BYHWD group, the number of BrdU/Nestin, BrdU/ NeuN, and BrdU/GFAP positive cells significantly decreased (P < 0.01), and the protein expression of BDNF and VEGF were significantly reduced in the qi supplementing group and the blood activating group (P < 0.01).

CONCLUSIONSBYHWD could significantly improve neurogenesis and neurological function recovery after focal cerebral ischemia in rats. Its mechanisms might be related to up-regulating protein expression of BDNF and VEGF. Drugs for qi supplementing and drugs for blood activating had synergistic effects.

Animals ; Brain Ischemia ; drug therapy ; metabolism ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Neurogenesis ; drug effects ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo observe the effect of Draconis Sanguis-containing serum on the expressions of NGF, BDNF, CNTF, LNG-FR, TrkA, GDNF, GAP-43 and NF-H in Schwann cells, and investigate the possible mechanism of Draconis Sanguis to promote peripheral nerve regeneration.

METHODSD rats were randomly divided into 2 groups: the Draconis Sanguis group (orally administered with Draconis Sanguis-containing balm solution) and the blank group (equivoluminal balm) to prepare Draconis Sanguis-containing serum and blank control serum. Schwann cells were extracted from double sciatic nerves of three-day-old SD rats, divided into 2 groups: the Draconis Sanguis group and the blank control group, and respectively cultured with 10% Draconis Sanguis-containing serum or blank control serum. The mRNA expressions of NGF, BDNF, CNTF and other genes in Schwann cells were measured by RT-PCR analysis 48 hours later.

RESULTMost of the Schwann cells were bipolar spindle and arranged shoulder to shoulder or end to end under the microscope and identified to be positive with the immunocytochemical method. To compare with the blank group, mRNA expressions of NGF, LNGFR, GDNF and GAP-43 significantly increased (P < 0.01). Whereas that of BDNF decreased significantly (P < 0.05), and so did that of TrkA, CNTF (P < 0.01), with no remarkable difference in NF-H-mRNA.

CONCLUSIONTraditional Chinese medicine Draconis Sanguis may show effect in nerve regeneration by up-regulating mRNA expressions of NGF, LNGFR, GDNF and GAP-43 and down-regulating mRNA expressions of TrkA, BDNF and CNTF.

Animals ; Arecaceae ; chemistry ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Cells, Cultured ; Ciliary Neurotrophic Factor ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; GAP-43 Protein ; genetics ; metabolism ; Gene Expression ; drug effects ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; metabolism ; Male ; Nerve Growth Factor ; genetics ; metabolism ; Nerve Regeneration ; drug effects ; Neurofilament Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA ; genetics ; metabolism ; Schwann Cells ; drug effects ; physiology ; Serum ; chemistry