An experimental study of artificial murine bladder reflex arc established by abdominal reflex / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The neurogenic bladder dysfunction caused by spinal cord injury is difficult to treat clinically. The aim of this research was to establish an artificial bladder reflex arc in rats through abdominal reflex pathway above the level of spinal cord injury, reinnervate the neurogenic bladder and restore bladder micturition.</p><p><b>METHODS</b>The outcome was achieved by intradural microanastomosis of the right T13 ventral root to S2 ventral root with autogenous nerve grafting, leaving the right T13 dorsal root intact. Long-term function of the reflex arc was assessed from nerve electrophysiological data and intravesical pressure tests during 8 months postoperation. Horseradish peroxidase (HRP) tracing was performed to observe the effectiveness of the artificial reflex.</p><p><b>RESULTS</b>Single stimulus (3 mA, 0.3 ms pulses, 20 Hz, 5-second duration) on the right T13 dorsal root resulted in evoked action potentials, raised intravesical pressures and bladder smooth muscle, compound action potential recorded from the right vesical plexus before and after the spinal cord transaction injury between L5 and S4 segmental in 12 Sprague-Dawley rats. There were HRP labelled cells in T13 ventral horn on the experimental side and in the intermediolateral nucleus on both sides of the L6-S4 segments after HRP injection. There was no HRP labelled cell in T13 ventral horn on the control side.</p><p><b>CONCLUSION</b>Using the surviving somatic reflex above the level of spinal cord injury to reconstruct the bladder autonomous reflex arc by intradural microanastomosis of ventral root with a segment of autologous nerve grafting is practical in rats and may have clinical applications for humans.</p>

Transplanted bone marrow stromal cells improve cognitive dysfunction due to aging hypoperfusion in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.</p><p><b>METHODS</b>Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group, D-gal + 2VO group, D-gal + 2VO + saline water group, and D-gal + 2VO + BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation; moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).</p><p><b>RESULTS</b>Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal + 2VO + BMSC group showed significant improvement than the D-gal + 2VO group but was still obviously worse than the control group (both P < 0.05). There was no significant difference in swimming speed for all 5 groups.</p><p><b>CONCLUSIONS</b>D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.</p>

Unilateral amyloid-beta25-35 injection into the rat amygdala increases the expressions of aberrant tau phosphorylation kinases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in beta-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression.</p><p><b>METHODS</b>Twenty-four male rats were divided into three groups, and each group had 8 rats: control, sham-operated, and Abeta(25-35) injected AD model groups. AD rat models were created by unilateral injections of Abeta(25-35) into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 (PHF-1) antibody and paired helical filament-tau (AT8) antibody. The expressions of glycogen synthase kinase-3beta (GSK-3beta) and p38 mitogen-activated protein kinase (P(38)MAPK) mRNA were observed by in situ hybridization.</p><p><b>RESULTS</b>Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 (PHF-1) in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density (OD) values of the proteins were significantly higher (AT8: in CA2: 0.318 +/- 0.037 vs. 0.135 +/- 0.028, 0.136 +/- 0.031; in frontal cortex: 0.278 +/- 0.040 vs. 0.130 +/- 0.028, 0.190 +/- 0.037. PHF-1: in CA2: 0.386 +/- 0.034 vs. 0.139 +/- 0.010, 0.193 +/- 0.041; in frontal cortex: 0.395 +/- 0.050 vs. 0.159 +/- 0.030, 0.190 +/- 0.044, respectively, P < 0.01); the number of GSK-3beta mRNA and P(38)MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus (GSK-3beta-mRNA: in CA2: 0.384 +/- 0.012 vs. 0.190 +/- 0.015, 0.258 +/- 0.064; in frontal cortex: 0.398 +/- 0.018 vs. 0.184 +/- 0.031, 0.218 +/- 0.049. P(38)MAPK mRNA: in CA2: 0.409 +/- 0.038 vs. 0.161 +/- 0.041, 0.189 +/- 0.035; in frontal cortex: 0.423 +/- 0.070 vs. 0.160 +/- 0.032, 0.203 +/- 0.053, respectively, P < 0.01).</p><p><b>CONCLUSION</b>Unilateral injection of Abeta(25-35) into the rat amygdala increases the generation of aberrant phosphorylated tau by increasing GSK-3beta and P(38)MAPK gene expression, that accelerates the process of Alzhemer's disease.</p>

Effects of L-lysine monohydrochloride on insulin and blood glucose levels in spinal cord injured rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperglycemia in brain and spinal cord could aggravate neurologic impairment. Recent studies showed that L-lysine monohydrochloride (LMH) could increase the insulin secretion and regulate the blood glucose level. The aim of the present study was to investigate the effects of LMH on pancreatic islet B cells, the levels of endogenous insulin and blood glucose in spinal cord injured rats.</p><p><b>METHODS</b>Forty male Wistar rats were divided into four groups, namely, normal control group, model group, high-dose LMH group (621.5 mg/kg equal to LMH 1/8 LD50), and low-dose LMH group (310.8 mg/kg equal to LMH 1/16 LD50). The model of spinal cord injured rat was established by hemi-transection at the lower right thoracic spinal cord. LMH was administered via intraperitoneal injection once spinal cord injury was produced in rats. All rats were sacrificed 48 hours after spinal cord injured. The effects of LMH on pancreatic islet B cells, the content of endogenous insulin, and the level of blood glucose were observed with immunohistochemical method, radioimmunoassay method, and biochemical analyzer, respectively.</p><p><b>RESULTS</b>The insulin immunohistochemical intensities of islet B cells were significantly weaker in model group than those in normal control group (P < 0.01). The levels of endogenous insulin were significantly lower and the blood glucose levels were significantly higher in model group than those in normal control group (P < 0.01). The insulin immunohistochemical intensities of islet B cells were significantly stronger in high-dose LMH group than those in model group (P < 0.05). In addition, we found that the levels of endogenous insulin were significantly higher and the blood glucose levels were significantly lower in high-dose LMH group than those in model group (P < 0.05). There were no significant differences in the insulin immunohistochemical intensities of islet B cells, the levels of endogenous insulin and the blood glucose between low-dose LMH group and model group (P > 0.05).</p><p><b>CONCLUSION</b>LMH, but dose-dependent, might participate in the regulation of pancreatic islet B cells, and then reduce the blood glucose levels in the spinal cord injured rats.</p>

Treatment of diabetic peripheral neuropathy / 上海第二医科大学学报

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus in nervous system. However, the pathogenesis is still unkown. Therapeutic options are mainly pathogenetically oriented therapy and symptomatic therapy. With an increasing understanding of the pathogenesis of DPN, many new therapies have emerged. Comprehensive therapy targeting different pathogenesis will be frequently applied in the future. In this article, the common therapy and advance in treatment of DPN are reviewed.

Toxic influence of chronic oral administration of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide, has been repeatedly suggested as a potential etiologic factor for the development of Parkinson's disease (PD), owing to its structural similarity to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This study aimed to observe the influence of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice.</p><p><b>METHODS</b>A total of 24 male C57BL/6 mice were assigned randomly to 3 groups: control group (treated by saline), PQ treated group, and MPTP treated group. Mice in PQ treated group were taken orally with PQ (10 mg/kg) daily for four months. Locomotor activity was measured. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD), and tyrosine hydroxylase (TH) positive neurons were detected by using immunohistochemistry. At the same time, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) in substantia nigra were measured by spectrophotometry. mRNA expression of dopamine transporter (DAT) in dopaminergic neurons of substantia nigra was also determined by reverse transcription (RT)-PCR technique.</p><p><b>RESULTS</b>Locomotor activities were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined. The activities of SOD and GSH-PX were decreased, and the content of MDA was increased in PQ treated mice compared with that in control group. Numbers of TH positive neurons and the mRNA expression of DAT in substantia nigra of mice were also decreased after PQ taken orally for four months.</p><p><b>CONCLUSIONS</b>The present study suggests that chronic oral administration of PQ could trigger dopaminergic neuron degeneration. Oxidative stress could be involved in the pathogenic mechanism of PD induced by PQ.</p>