scholarly journals Reducing neuronal apoptosis in pontine micturition center by nerve root transfer to reconstruct bladder function after spinal cord injury

2019 ◽  
Author(s):  
Ronghua Yu ◽  
Gang Yin ◽  
Jianguo Zhao ◽  
Huihao Chen ◽  
Depeng Meng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nerve Root ◽  
Neuronal Apoptosis ◽  
Nerve Transfer ◽  
Bladder Function ◽  
Sprague Dawley ◽  
Nerve Roots ◽  
Sprague Dawley Rats ◽  
Cord Injury

Abstract Background: The neuronal apoptosis is increased after spinal cord injury (SCI), but anastomosing the normal nerve roots above SCI level to the injury sacral nerve roots can enhance functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival and restoration of bladder function. Methods: Adult female Sprague Dawley rats (N = 90, 9–10 weeks old, 240-260 grams weight) were randomly divided into three groups (N = 30). We anastomosed the dorsal and ventral roots of proximal L4 and distal S2 to reconstruct the rat bladder–spinal cord–cerebral nerve afferent and efferent pathways in Sprague Dawley rats after spinal cord transection. We examined pontine neuronal morphology and apoptosis using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) at different time points (1 day, 1 week, and 1, 3, or 6 months) after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. Results: After nerve roots reconstruction, Group A compared with Group B, Bcl-2 expression increased significantly, Bax expression decreased significantly, Bcl-2/Bax ratio increased, the number of apoptotic neurons decreased, and the number of apoptotic bodies within neurons decreased significantly as observed by TEM.Conclusion: These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This method can be used as a new approach for reconstructing bladder function after spinal cord injury.

scholarly journals Reducing Neuron Apoptosis in the Pontine Micturition Center by Nerve Root Transfer for Restoration of Micturition Function after Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ronghua Yu ◽  
Gang Yin ◽  
Jianguo Zhao ◽  
Huihao Chen ◽  
Depeng Meng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nerve Root ◽  
Neuronal Apoptosis ◽  
Nerve Transfer ◽  
Tunel Staining ◽  
Nerve Roots ◽  
Cord Injury ◽  
Group A ◽  
Group B

Objective. The rate of neuronal apoptosis increases after spinal cord injury (SCI). Anastomosing the normal nerve roots above the SCI level to the injured sacral nerve roots can enhance the functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival. Methods. Sprague–Dawley rats were randomly divided into three groups: Group A, reconstruction of afferent and efferent nerve pathways of the bladder after SCI; Group B, SCI only; and Group C, control group. We examined pontine neuronal morphology using hematoxylin and eosin (H&E) staining after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. The number of apoptotic neurons was determined by TUNEL staining. We examined pontine neuronal apoptosis by transmission electron microscopy (TEM) at different time points. Results. H&E staining demonstrated that the number of neurons had increased in Group A, but more cells in Group B displayed nuclear pyknosis, with the disappearance of the nucleus. Compared with Group B, Group A had significantly higher Bcl-2 expression, significantly lower Bax expression, and a significantly higher Bcl-2/Bax ratio. The number of apoptotic neurons and neuron bodies in Group A was significantly lower than that in Group B, as indicated by TUNEL staining and TEM. Conclusions. These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This result further suggests that lumbosacral nerve transfer can be used as a new approach for reconstructing bladder function after spinal cord injury.

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.

Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

2016 ◽  
Vol 25 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Sergiy V. Kushchayev ◽  
Morgan B. Giers ◽  
Doris Hom Eng ◽  
Nikolay L. Martirosyan ◽  
Jennifer M. Eschbacher ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuroprotective Effect ◽  
Scar Tissue ◽  
Treated Group ◽  
Secondary Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cord Injury ◽  
Behavioral Assessments

OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway

2021 ◽  
Author(s):  
Lu Wang ◽  
Yuan-Bo Fu ◽  
Yi Liu ◽  
Na-Na Yang ◽  
Si-Ming Ma ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Detrusor Overactivity ◽  
Bladder Function ◽  
Potential Candidate ◽  
Neurogenic Detrusor Overactivity ◽  
Afferent Activity ◽  
Sprague Dawley ◽  
Pressure Threshold ◽  
Cord Injury

Abstract Background Activation of muscarinic receptors located in bladder sensory pathways is generally considered to be the primary contributor for driving the pathogenesis of neurogenic detrusor overactivity following spinal cord injury. The present study is undertaken to examine whether moxibustion improves neurogenic detrusor overactivity via modulating the abnormal muscarinic receptor pathway. Methods Female Sprague-Dawley rats were subjected to spinal cord injury with T9-10 spinal cord transection. Fourteen days later, animals were received moxibustion treatment for one week. Urodynamic parameters and pelvic afferents discharge were measured. Acetylcholine and adenosine triphosphate content in the voided cystometry fluid were determined. Expressions of M2, M3 and P2X3 receptor in the bladder mucosa were evaluated. Results Moxibustion treatment prevented the development of detrusor overactivity in SCI rats, with an increase in the intercontraction interval and micturition pressure threshold and a decrease in afferent activity during filling. The expression of M2, but not M3, was markedly suppressed by moxibustion, accompanied by a reduction in the level of ATP and P2X3. M2 receptor antagonist methoctramine hemihydrate had similar effects to moxibustion on bladder function and afferent activity, while the M2-preferential agonist oxotremorine methiodide abolished the beneficial effects of moxibustion. Conclusions Moxibustion is a potential candidate for treatment of neurogenic bladder overactivity in a rat model of spinal cord injury possibly through inhibiting the M2/ATP/P2X3 pathway.

scholarly journals Enhancing KCC2 activity decreases hyperreflexia and spasticity after chronic SCI

2020 ◽  
Author(s):  
Jadwiga N. Bilchak ◽  
Kyle Yeakle ◽  
Guillaume Caron ◽  
Dillon C. Malloy ◽  
Marie-Pascale Côté
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Side Effects ◽  
Sprague Dawley ◽  
Rehabilitation Programs ◽  
Rate Dependent ◽  
Chloride Homeostasis ◽  
Sprague Dawley Rats ◽  
Early Implementation ◽  
Cord Injury

AbstractAfter spinal cord injury (SCI), the majority of individuals develop spasticity, a debilitating condition involving involuntary movements, co-contraction of antagonistic muscles, and hyperreflexia. By acting on GABAergic and Ca2+-dependent signaling, current anti-spastic medications lead to serious side effects, including a drastic decrease in motoneuronal excitability which impairs motor function and rehabilitation efforts. Exercise, in contrast, decreases spastic symptoms without decreasing motoneuron excitability. These functional improvements coincide with an increase in expression of the chloride co-transporter KCC2 in lumbar motoneurons. Thus, we hypothesized that spastic symptoms can be alleviated directly through restoration of chloride homeostasis and endogenous inhibition by increasing KCC2 activity. Here, we used the recently developed KCC2 enhancer, CLP257, to evaluate the effects of acutely increasing KCC2 extrusion capability on spastic symptoms after chronic SCI. Sprague Dawley rats received a spinal cord transection at T12 and were either bike-trained or remained sedentary for 5 weeks. Increasing KCC2 activity in the lumbar enlargement improved the rate-dependent depression of the H-reflex and reduced both phasic and tonic EMG responses to muscle stretch in sedentary animals after chronic SCI. Furthermore, the improvements due to this pharmacological treatment mirror those of exercise. Together, our results suggest that pharmacologically increasing KCC2 activity is a promising approach to decrease spastic symptoms in individuals with SCI. By acting to directly to restore endogenous inhibition, this strategy has potential to avoid severe side effects and improve the quality of life of affected individuals.Significance StatementSpasticity is a condition that develops after spinal cord injury (SCI) and causes major complications for individuals. We have previously reported that exercise attenuates spastic symptoms after SCI through an increase in expression of the chloride co-transporter KCC2, suggesting that restoring chloride homeostasis contributes to alleviating spasticity. However, the early implementation of rehabilitation programs in the clinic is often problematic due to co-morbidities. Here, we demonstrate that pharmacologically enhancing KCC2 activity after chronic SCI reduces multiple signs of spasticity, without the need for rehabilitation.

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