MP82-03 NEUTRALIZATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR INCREASES SYNERGISTIC ACTIVITY OF EXTERNAL URETHRAL SPHINCTER WITH REDUCTION OF ACID-SENSING ION CHANNELS IN MICE WITH SPINAL CORD INJURY

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Naoki Wada ◽  
Takahiro Shimizu ◽  
Nobutaka Shimizu ◽  
Pradeep Tyagi ◽  
William de Groat ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Ion Channels ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Synergistic Activity ◽  
Urethral Sphincter ◽  
External Urethral Sphincter ◽  
Acid Sensing Ion Channels ◽  
Cord Injury

scholarly journals Therapeutic effects of inhibition of brain-derived neurotrophic factor on voiding dysfunction in mice with spinal cord injury

2019 ◽  
Vol 317 (5) ◽  
pp. F1305-F1310 ◽  
Author(s):  
Naoki Wada ◽  
Takahiro Shimizu ◽  
Nobutaka Shimizu ◽  
Masahiro Kurobe ◽  
William C. de Groat ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Transient Receptor Potential Channels ◽  
Emg Activity ◽  
Therapeutic Effects ◽  
External Urethral Sphincter ◽  
Antibody Treatment ◽  
Cord Injury

We investigated the involvement of brain-derived neurotrophic factor (BDNF) in bladder and urethral dysfunction using spinal cord-injured mice. We evaluated bladder and urethral function of female mice with 4-wk spinal cord injury (SCI) by filling cystometry and electromyography (EMG) of the external urethral sphincter (EUS) under a conscious condition. Anti-BDNF antibodies (10 μg·kg−1·h−1) were administered in some mice for 1 wk before the evaluation. Bladder and spinal (L6−S1) BDNF protein levels were examined by ELISA. Transcript levels of transient receptor potential channels or acid-sensing ion channels (Asic) in L6−S1 dorsal root ganglia were evaluated by RT-PCR. Voided volume and voiding efficiency were significantly increased without any changes in nonvoiding contractions, and the duration of reduced EMG activity during the voiding phase was significantly prolonged in anti-BDNF antibody-treated SCI mice. Compared with spinal cord-intact mice, SCI mice showed increased concentrations of bladder and spinal BDNF. Anti-BDNF antibody treatment decreased bladder and spinal BDNF protein concentrations of SCI mice. Asic2 and Asic3 transcripts were significantly increased after SCI but decreased after anti-BDNF antibody administration. These results indicate that upregulated expression of bladder and spinal BDNF is involved in the emergence of inefficient voiding in SCI mice. Thus, BDNF-targeting treatment could be an effective modality for the treatment of voiding problems, including inefficient voiding and detrusor sphincter dyssynergia after SCI.

scholarly journals Human Brain–Derived Neurotrophic Factor Gene-Modified Bone Marrow Mesenchymal Stem Cells Combined With Erythropoietin Can Improve Acute Spinal Cord Injury

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582091093
Author(s):  
YongLei Li ◽  
Hongchen Wang ◽  
Xiaofang Ding ◽  
Jiancheng Shen ◽  
Haitao Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Bdnf Gene ◽  
Factor Gene ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Objective: To assess the effect as well as mechanism of bone marrow mesenchymal stem cells (BMSCs) modified by the human brain–derived neurotrophic factor gene combined with erythropoietin (EPO) in the treatment of acute spinal cord injury (SCI) in rats. Methods: The Brain-derived neurotrophic factor (BDNF) gene was transected by a virus vector. Rats with SCI were randomly split into following groups: The normal saline (NS) group, the EPO group, The Basso, Beattie, and Bresnahan scores, messenger RNA BDNF expression, and apoptosis rates were compared between the 4 groups at 1, 3, 7, 14, and 21 days after SCI. Results: At 7, 14, and 21 days after operation, the expression of the BDNF gene in the other 3 groups was higher than that of the NS group, and the difference was statistically significant ( P < .05). The apoptosis rate in the combined group was less than that of NS, EPO, and BDNF/BMSC groups, and the differences were statistically significant ( P < .05). Conclusion: Brain-derived neurotrophic factor gene-modified BMSC transplantation combined with EPO can promote the repair of nerve function after SCI in rats.

scholarly journals α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury

2016 ◽  
Vol 311 (5) ◽  
pp. R971-R978 ◽  
Author(s):  
Hirokazu Ishida ◽  
Hiroki Yamauchi ◽  
Hideaki Ito ◽  
Hironobu Akino ◽  
Osamu Yokoyama
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lower Urinary Tract Dysfunction ◽  
Urethral Sphincter ◽  
Sprague Dawley ◽  
External Urethral Sphincter ◽  
Detrusor Sphincter Dyssynergia ◽  
Sphincter Electromyography ◽  
Sprague Dawley Rats ◽  
Cord Injury

Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.

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