Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency.

BACKGROUND: Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic-adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear. METHODS AND OBJECTIVES: The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic-adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine-immune network associated with SCI-IDS was further elucidated. RESULTS: The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses. CONCLUSIONS: To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

Reliability and validity of the fall risk self-assessment scale for community-dwelling older people in China: a pilot study.

BACKGROUND: Falls are a common and serious public health issue among older adults, contributing to the loss of independence, psychological distress, and incapability to engage in meaningful occupations, etc. However, there is a lack of abundant information about the fall risk self-evaluation scale for community-dwelling older people. Therefore, this study aimed to evaluate the preliminary reliability and validity of the fall risk self-assessment scale (FRSAS) among community-dwelling older adults. METHODS: A cross-sectional study was conducted. A total of 230 individuals aged 65 years and over were recruited by a convenience sampling between October and December 2020 from three communities in Haidian district, Beijing. Eligible participants were required to fill in the general condition questionnaire and the fall risk self-assessment scale. The reliability and validity were analyzed by using SPSS 20.0. RESULTS: Two hundred twenty-two participants completed the assessment as required (the completion rate was 96.52%). The most items of FRSAS were understood by older adults, which was completed in 10 min. Cronbach's α and intraclass correlation coefficient ICC (2,1) of the scale were 0.757 and 0.967 respectively, suggesting good internal consistency and test-retest reliability. Exploratory factor analysis yielded 14 factors that explained 61.744% of the variance. Five items failed to be categorized into any factors because the factor loading of these items was less than 0.4. A future large-sample study needs to be conducted to explore its construct validity. The total scores and dimensional scores except for C-dimension showed significant differences between participants who had experienced a fall in the previous 6 months and those who had not (P < 0.05), indicating good discriminant validity. CONCLUSIONS: The fall risk self-assessment scale including 41 items demonstrated relatively high feasibility as well as satisfactory results in the internal consistency, test-retest reliability, and discriminant validity. TRIAL REGISTRATION: Registration number: ChiCTR2000038856 ; Date of registration: 7 Oct 2020.

Diagnosing Muscle Atrophy by Use of a Comprehensive Method of Assessing the Elastic Properties of Muscle During Passive Stretching.

OBJECTIVE. The purpose of this study was to apply a new method for quantitatively assessing atrophied muscles by use of sonoelastography. SUBJECTS AND METHODS. B-mode sonography and shear-wave elastography of the gastrocnemius muscle (GM) were performed on 12 patients and 32 healthy control volunteers during passive stretching induced by ankle rotation from 40° plantar flexion to 30° dorsiflexion. The GM length and corresponding elastic moduli were measured consecutively per frame. The elastic modulus-length curve was created by plotting the elastic modulus against the GM length during passive stretching. Three physiologically significant parameters-slack elasticity modulus (E0), slack length (l0), and passive elastic coefficient (k)-were estimated from the measured elasticity modulus-length curve to quantify the elastic properties of the GM. RESULTS. All results showed a smooth exponential curve. In the state of relaxation, atrophied GM was softer than GM of healthy control subjects. However, when the muscles were passively stretched from a state of slack to tension, k was significantly greater for the patients with atrophied GMs than for the control subjects. Furthermore, the diagnostic accuracy of k for muscle atrophy was greater than that of E0. CONCLUSION. Increased elastic stiffness may be considered a positive finding for the characterization of muscle atrophy. Because of its high diagnostic accuracy and reproducibility, the elastic modulus-length curve can provide new insights into the diagnosis of muscle disease and allows monitoring of muscle function in rehabilitation.

Prediction of Prolonged Length of Stay for Stroke Patients on Admission for Inpatient Rehabilitation Based on the International Classification of Functioning, Disability, and Health (ICF) Generic Set: A Study from 50 Centers in China.

BACKGROUND This study aimed to develop a risk prediction model for prolonged length of stay (LOS) in stroke patients in 50 inpatient rehabilitation centers in 20 provinces across mainland China based on the International Classification of Functioning, Disability, and Health (ICF) Generic Set case mix on admission. MATERIAL AND METHODS In this cohort study, 383 stroke patients were included from inpatient rehabilitation settings of 50 hospitals across mainland China. Independent predictors of prolonged LOS were identified using multivariate logistic regression analysis. A prediction model was established and then evaluated by receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow test. RESULTS Multivariate logistic regression analysis showed that the type of medical insurance and the performance of daily activities (ICF, d230) were associated with prolonged LOS (P<0.05). Age and mobility level measured by the ICF Generic Set demonstrated no significant predictive value. The prediction model showed acceptable discrimination shown by an area under the curve (AUC) of 0.699 (95% CI, 0.646-0.752) and calibration (χ²=11.66; P=0.308). CONCLUSIONS The risk prediction model for prolonged LOS in stroke patients in 50 rehabilitation centers in China, based on the ICF Generic Set, showed that the scores for the type of medical insurance and the performance of daily activities (ICF, d230) on admission were independent predictors of prolonged LOS. This prediction model may allow stakeholders to estimate the risk of prolonged LOS on admission quantitatively, facilitate the financial planning, treatment regimens during hospitalization, referral after discharge, and reimbursement.

Transcriptomic analysis of α-synuclein knockdown after T3 spinal cord injury in rats.

BACKGROUND: Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. RESULT: The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype ß2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. CONCLUSION: Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.

Proteomics and Transcriptomics Analysis Reveals Clues into the Mechanism of the Beneficial Effect of Electrical Stimulation on Rat Denervated Gastrocnemius Muscle.

BACKGROUND/AIMS: The aim of this study was to confirm the beneficial effects of electrical stimulation on denervated skeletal muscle and explore a novel underlying mechanism. METHODS: Morphological and contractile analyses were performed on rats allocated to three groups: sham operation (SHAM), denervated (DN), and denervated and electrical stimulation (DN-SM). Proteomics, transcriptomics, bioinformatics, and skeletal muscle functional modules analysis were conducted to determine the changes in molecular expression resulting from electrical stimulation. RESULTS: Rats in the DN-SM group maintained a greater muscle mass, muscle fiber diameter, and contractile properties than those of the DN group. A total of 66 proteins and 402 mRNAs were differentially expressed between groups. Bioinformatics analysis suggested that the FoxO and p53 signaling pathways play significant roles in structural protection. Skeletal muscle function modules analysis suggested that anti-apoptosis proteins (KCNA7, KCNJ11), muscle fiber type related proteins (TNNI1, TNNT1, ACTN2, MYOZ2, MYLK2, and MYOM2), M-line structural protein (MYOM2), dystrophin combined with glycoprotein complex proteins (SGCB, SGCD, and DTNA), and anti-fibrosis-related proteins (POSTN, COL1A1, COL1A2, COL6A1, COL6A2, COL6A3, FN1, and LUM), may be related to the effects of electrical stimulation. CONCLUSION: Electrical stimulation can maintain the denervated muscle morphology and function. Anti-apoptosis, inhibition of muscle fiber type differentiation, protection against dystrophin-associated-glycoprotein complex mutation, and anti-fibrosis are potential mechanisms of the beneficial effects of electrical stimulation.

Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with spinal cord injury.

BACKGROUND: The prognosis of spinal cord injury (SCI) is closely related to secondary injury, which is dominated by neuroinflammation. There is evidence that α-synuclein aggregates after SCI and that inhibition of α-synuclein aggregation can improve the survival of neurons after SCI, but the mechanism is still unclear. This study was designed to investigate the effects of α-synuclein on neuroinflammation after SCI and to determine the underlying mechanisms. METHOD: A T3 spinal cord contusion model was established in adult male Sprague-Dawley rats. An SNCA-shRNA-carrying lentivirus (LV-SNCA-shRNA) was injected into the injury site to block the expression of α-synuclein (forming the SCI+KD group), and the SCI and sham groups were injected with an empty vector. Basso-Beattie-Bresnahan (BBB) behavioural scores and footprint analysis were used to detect motor function. Inflammatory infiltration and myelin loss were measured in the spinal cord tissues of each group by haematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining, respectively. Immunohistochemistry, Western blot analysis, and RT-qPCR were used to analyse protein expression and transcription levels in the tissues. Immunofluorescence was used to determine the morphology and function of glial cells and the expression of matrix metalloproteinase-9 in the central canal of the spinal cord. Finally, peripheral serum cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the SCI group, the SCI+KD group exhibited reduced inflammatory infiltration, preserved myelin, and functional recovery. Specifically, the early arrest of α-synuclein inhibited the pro-inflammatory factors IL-1ß, TNF-α, and IL-2 and increased the expression of the anti-inflammatory factors IL-10, TGF-ß, and IL-4. The neuroinflammatory response was regulated by reduced proliferation of Iba1+ microglia/macrophages and promotion of the shift of M1-polarized Iba1+/iNOS+ microglia/macrophages to M2-polarized Iba1+/Arg1+ microglia/macrophages after injury. In addition, compared with the SCI group, the SCI+KD group also exhibited a smaller microglia/astrocyte (Iba1/GFAP) immunostaining area in the central canal, lower MMP-9 expression, and improved cerebrospinal barrier function. CONCLUSION: Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation, improves blood-cerebrospinal barrier function, promotes functional recovery, reduces microglial activation, and promotes the polarization of M1 microglia/macrophages to an M2 phenotype to confer a neuroprotective immune microenvironment in rats with SCI.

MicroRNA-219 Inhibits Proliferation and Induces Differentiation of Oligodendrocyte Precursor Cells after Contusion Spinal Cord Injury in Rats.

MicroRNA-219 (miR-219) regulates the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) during central nervous system (CNS) development. OPCs only differentiate into oligodendrocytes (OLs) in the healthy CNS, but can generate astrocytes (As) after injury. We hypothesized that miR-219 may modulate OPC proliferation and differentiation in a cervical C5 contusion spinal cord injury (SCI) model. After injury, we observed a decrease in the miR-219 level and quantity of OLs and an increase in the number of OPCs and As. Silencing of miR-219 by its antagomir in vivo produced similar results, but of greater magnitude. Overexpression of miR-219 by its agomir in vivo increased the number of OLs and suppressed generation of OPCs and As. Luxol fast blue staining confirmed that SCI caused demyelination and that the extent of demyelination was attenuated by miR-219 overexpression, but aggravated by miR-219 reduction. Monocarboxylate transporter 1 (MCT-1) may be implicated in the regulation of OPC proliferation and differentiation mediated by miR-219 following contusion SCI. Collectively, our data suggest that miR-219 may mediate SCI-induced OPC proliferation and differentiation, and MCT-1 may participate in this process as a target of miR-219.

Electrical stimulation influences satellite cell differentiation after sciatic nerve crush injury in rats.

INTRODUCTION: Electrical stimulation is often used to prevent muscle atrophy and preserve contractile function, but its effects on the satellite cell population after nerve injury are not well understood. In this study we aimed to determine whether satellite cell differentiation is affected by electrical stimulation after nerve crush. METHODS: The sciatic nerves of Sprague-Dawley (SD) rats were crushed. Half of the injured rats received daily electrical stimulation of the gastrocnemius muscle, and the others did not. Tests for detecting paired box protein 7 (Pax7), myogenic differentiation antigen (MyoD), embryonic myosin heavy chain (eMyHC), and force production were performed 2, 4, and 6 weeks after injury. RESULTS: More Pax7+/MyoD+ nuclei in stimulated muscles were observed than in non-stimulated muscles. eMyHC expression was elevated in stimulated muscles and correlated positively with enhanced force production. CONCLUSIONS: Increased satellite cell differentiation is correlated with preserved muscle function in response to electrical stimulation after nerve injury.

Diagnostic Ultrasound in the Evaluation of Stiff Shoulder: Association of Axillary Recess Thickness with Standard Clinical Measures.

OBJECTIVES: Stiff shoulder, including primary and secondary types, poses diagnostic challenges due to vague definitions and criteria. This study evaluates the diagnostic potential of ultrasound-measured axillary recess (AR) thickness in shoulder stiffness. DESIGNS: In this cross-sectional study, 35 patients with unilateral shoulder stiffness were assessed. AR thickness was measured using high-resolution ultrasound. Parameters like passive range of motion (PROM), Numerical Rating Scale (NRS), and Constant-Murley (CM) score were evaluated to find correlations with AR thickness. RESULTS: The average age was 50.7 years, and mean BMI was 22.7. AR thickness in stiff shoulders (average 3.19 mm) was significantly higher than in unaffected shoulders (average 1.93 mm, p < 0.001). A cutoff of 3.0 mm for AR thickness yielded 73.3% sensitivity and 84.6% specificity for primary stiffness; 2.6 mm cutoff resulted in 57.9% sensitivity and 88.2% specificity for secondary stiffness. Significant correlations were found between AR thickness and PROM, especially in shoulder external rotation and extension. CONCLUSION: AR thickness measured by ultrasound might serve as a valuable diagnostic and evaluation parameter in shoulder stiffness.

Applying Concepts of Curriculum Design and Cultural Adaptation: Collaborating on a Dual-Degree Occupational Therapy Program in Mainland China.

Occupational therapy is a profession with origins rooted in Western values. As culture plays an important role in shaping theory and practice, the curriculum design of academic programs that train future rehabilitation professionals should reflect the local context. As part of an international partnership, a dual-degree graduate program in occupational therapy was established between a Chinese and an American university. A team composed of members from both institutions collaborated on culturally adapting an entry-level master's program in occupational therapy for China, based on a U.S. program, which welcomed its first cohort in September 2019. This article details the timeline and process of program design and adaptation from conception, through implementation to evaluation and revision, with the aim of offering a framework for curriculum adaptation of other academic programs in the U.S. and internationally. The adapted curriculum includes the program mission, vision, and philosophy; the curriculum model with program outcomes and threads; the program scope and sequence; materials and resources; and course-specific objectives, learning activities, and assessments. The authors also share lessons learned through this experience of international collaboration as well as next steps for program evaluation and sustainability. The detailed overview of this international collaboration offers suggestions for individuals and institutions seeking to develop global partnerships and adapt curricula across cultural contexts.

Quantitative assessment of biceps brachii muscle stiffness by using Young's modulus-Angle curve during passive stretching in stroke patients.

Purpose: This study aims to use shear wave elastography (SWE) to dynamically describe the characteristics of biceps brachii muscle stiffness during passive stretching in healthy participants, investigate changes in the Young's modulus-angle curve under various states of muscle tone in stroke patients, and develop a new method for measuring muscle tone quantitatively. Methods: In total, 30 healthy volunteers and 54 stroke patients were evaluated for elbow flexor muscle tone on both sides using passive motion examination and were divided into groups based on their muscle tone status. The real-time SWE video of the biceps brachii and the Young's modulus data were recorded during the passive straightening of the elbow. The Young's modulus-elbow angle curves were created and fitted using an exponential model. The parameters yielded from the model were subjected to further intergroup analysis. Results: The repeatability of the Young's modulus measurement was generally good. During passive elbow extension, the Young's modulus of the biceps brachii steadily increased as muscle tone increased, and it increased faster when the modified Ashworth scale (MAS) score got higher. The exponential model's fitness was generally good. The curvature coefficient was significantly different between the MAS 0 group and the hypertonia groups (MAS 1, 1+, and 2 groups). Conclusion: The passive elastic characteristics of the biceps brachii are consistent with the exponential model. The Young's modulus-elbow angle curve of the biceps brachii changes in distinct ways depending on the muscle tone status. SWE can be used to quantify muscular stiffness during passive stretching as a new way of muscle tone evaluation, allowing for quantitative muscle tone evaluation and mathematical assessment of muscle mechanical properties in stroke patients.

[Observation of neuropeptides in bladder after spinal cord injury in rats].

OBJECTIVE: To observe the altered expressions of neuropeptide Y, substance P and vasoactive intestinal peptide in detrusor of SD rats after spinal cord injury and explore the relationship of the above neuropeptides and neurogenic bladder after spine cord injury. METHODS: Twenty male clean-grade SD rats, aged 6 weeks, were selected and randomized into spinal cord injury group (n = 10) and control group (n = 10). Rats in spinal cord injury group were smashed at T10 to cause spinal cord incomplete injury model by the weight drop method while laminectomy alone without smashing was administered in control group. At Week 1 post-operation, all rats were assessed by the maximum bladder capacity, bladder compliance and detrusor pressure for the confirmation of spastic bladder. And all detrusor specimens were marked with argentation and immunohistochemistry for the analyses of nerve fibers, neuropeptide Y, substance P and vasoactive intestinal peptide. The results were evaluated with semiquantitative method to observe the contents of nerve fiber and neuropeptides. RESULTS: At Week 1 post-operation, the mean maximum bladder compactly, mean maximum detrusor pressure and mean compliance in SCI rats was 0.71 ± 0.24 ml, 32.27 ± 3.12 cm H2O and 0.020 ± 0.009 ml/cm H2O versus 2.0 ± 0.4 ml, 21.0 ± 3.0 cm H2O and 0.090 ± 0.020 ml/cm H2O in normal control group respectively. And the differences were statistically significant (P < 0.01). Meanwhile, the mean content of nerve fibers of neurogenic bladder decreased markedly than that of normal control group (2.58 ± 0.13 vs 5.65 ± 0.26). As compared with the normal control group, the expressions of neuropeptide Y, substance P and vasoactive intestinal peptide (mean integrated optical density: 3.2 ± 0.5, 1.7 ± 0.4 and 2.1 ± 0.4 respectively) decreased dramatically in SCI rats. And the differences were statistically significant (P < 0.01). CONCLUSION: The number of nerve fibers and the content of neuropeptides significantly decrease in neurogenic bladder after spinal cord injury in rats. The reduction of neuropeptides may be correlated with the formation of neurogenic bladder after spinal cord injury.

Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth in spinal cord injury rats according to gene and co-expression network analyses.

The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of action is still unclear. In this study, different dietary feeding methods were used, and myelin expression and gene level changes were detected among different groups. We established 15 RNA-seq cDNA libraries from among 4 different groups. First, KEGG pathway enrichment of upregulated differentially expressed genes and gene set enrichment analysis of the ketogenic diet and normal diet groups indicated that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, protein-protein interaction analysis and visualization of iPath metabolic pathways, it was determined that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly. Second, through weighted gene co-expression network analysis showed that rats fed a ketogenic diet showed a significant reduction in the expression of genes involved in immune-related pathways, including those associated with immunity and infectious diseases. A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.

[Effects of highly selective dorsal rootlets rhizotomy on bladder function and penis erection in SD rats].

OBJECTIVE: To study the highly selective dorsal rhizotomy influence on bladder and penis erection function of SD rats. METHODS: Forty mature male SD rats of clean grades, with weight range of 300-350 g were selected. Ten rats were chosen to do electrophysiology study on dorsal rootlets of L6 and S1 segment. Changes in intravesical pressure (IVP) and intracavernous pressure (ICP) were investigated to define main segments which conducted to bladder and corpus cavernosum. Thirty rats were divided into two groups (A and B) on average at random. In group A, we made highly selective dorsal rhizotomy on the fascicle of conduction bladder detrusor muscle. In group B, we made highly selective dorsal rhizotomy on the fascicle of conduction corpus cavernosum. Changes of IVP and ICP after rhizotomy were investigated and recorded. RESULTS: The changes of IVP during electrostimulation were of no significant variation between L6 and S1 (P=0.972). With the changes of ICP during electrostimulation, S1 segment was of more significant variation than L6 segment, ΔICP of S1 was (13.05±8.41) cmH2O (1 cmH2O=0.098 kPa), while ΔICP of L6 was (6.88±2.76) cmH2O (P<0.01). There was no reasonable variation in IVP and ICP on the left and right dorsal rootlets of S1 segment (P was 0.623 and 0.828 respectively). In group A, there was significant variation in IVP, ΔIVP of before rhizotomy was (14.37±4.89) cmH2O, while after rhizotomy was (3.25±1.29) cmH2O (P<0.001) while no obvious variation in ICP (P=0.153) after highly selective rhizotomy on S1 dorsal rootlets. In group B, there was significant variation in ICP, ΔICP of before rhizotomy was (11.97±4.41) cmH2O, while after rhizotomy was (2.68±1.01) cmH2O (P<0.001), but no obvious variation in IVP (P=0.162) after highly selective rhizotomy on S1 dorsal rootlets. CONCLUSION: SD rats' different rootlets of S1 dorsal rootlets can be distinguished by microanatomy and electrostimulation. The IVP and ICP had distinct changes after highly selective dorsal rhizotomy. It could provide an experimental support to treat spastic bladder after spinal cord injury and retain at maximum reflexible erection function in the clinic.

[Selective innervation of sacral anterior rootlets to micturition and erection function in rats].

OBJECTIVE: To investigate the selective innervation of sacral anterior rootlets to micturition and erection function in SD rats. METHODS: Forty male SD rats of clean grade, aged 6 weeks old, were selected. Ten rats received a retrograde nerve tract tracing study. Thirty rats were chosen for an electro-physiological study. The L6, S1 spinal cord segment anterior rootlets of anesthetic rats were electrostimulated respectively. The intravesical pressure, urethral perfusion pressure and intracavernous pressure were recorded simultaneously and innervation effectiveness was analyzed. RESULTS: CB-HRP labeled neurons were observed mainly in L6 and S1 spinal cords. When some anterior rootlets of L6 and S1 were electrostimulated, the intravesical pressure rose gradually, but the urethral perfusion pressure and the intracavernous pressure curve changed slightly; when other rootlets of the same anterior root were stimulated, the urethral perfusion pressure could reach the peak; while others were stimulated, the intracavernous pressure rose quickly, but there were no great changes in intravesical pressure and urethral perfusion pressure. Some other rootlets might lead to the simultaneous changes of 2 or 3 above-mentioned pressures. CONCLUSION: The innervations of L6 and S1 anterior rootlets to rats' bladder detrusor, external urethral sphincter and penile cavernous body are significantly distinct. Different rootlets may be distinguished by microanatomy and electrostimulation.

Satellite cell proliferation and myofiber cross-section area increase after electrical stimulation following sciatic nerve crush injury in rats.

BACKGROUND: Electrical stimulation has been recommended as an effective therapy to prevent muscle atrophy after nerve injury. However, the effect of electrical stimulation on the proliferation of satellite cells in denervated muscles has not yet been fully elucidated. This study was aimed to evaluate the changes in satellite cell proliferation after electrical stimulation in nerve injury and to determine whether these changes are related to the restoration of myofiber cross-section area (CSA). METHODS: Sciatic nerve crush injury was performed in 48 male Sprague-Dawley rats. In half (24/48) of the rats, the gastrocnemius was electrically stimulated transcutaneously on a daily basis after injury, while the other half were not stimulated. Another group of 24 male Sprague-Dawley rats were used as sham operation controls without injury or stimulation. The rats were euthanized 2, 4, and 6 weeks later. After 5-bromo-2'-deoxyuridine (BrdU) labeling, the gastrocnemia were harvested for the detection of paired box protein 7 (Pax7), BrdU, myofiber CSA, and myonuclei number per fiber. All data were analyzed using two-way analysis of variance and Bonferroni post-hoc test. RESULTS: The percentages of Pax7-positive nuclei (10.81 ±â€Š0.56%) and BrdU-positive nuclei (34.29 ±â€Š3.87%) in stimulated muscles were significantly higher compared to those in non-stimulated muscles (2.58 ±â€Š0.33% and 1.30 ±â€Š0.09%, respectively, Bonferroni t = 15.91 and 18.14, P < 0.05). The numbers of myonuclei per fiber (2.19 ±â€Š0.24) and myofiber CSA (1906.86 ±â€Š116.51 µm) were also increased in the stimulated muscles (Bonferroni t = 3.57 and 2.73, P < 0.05), and both were positively correlated with the Pax7-positive satellite cell content (R = 0.52 and 0.60, P < 0.01). There was no significant difference in the ratio of myofiber CSA/myonuclei number per fiber among the three groups. CONCLUSIONS: Our results indicate that satellite cell proliferation is promoted by electrical stimulation after nerve injury, which may be correlated with an increase in myonuclei number and myofiber CSA.

α-Synuclein in traumatic and vascular diseases of the central nervous system.

α-Synuclein (α-Syn) is a small, soluble, disordered protein that is widely expressed in the nervous system. Although its physiological functions are not yet fully understood, it is mainly involved in synaptic vesicle transport, neurotransmitter synthesis and release, cell membrane homeostasis, lipid synthesis, mitochondrial and lysosomal activities, and heavy metal removal. The complex and inconsistent pathological manifestations of α-Syn are attributed to its structural instability, mutational complexity, misfolding, and diverse posttranslational modifications. These effects trigger mitochondrial dysfunction, oxidative stress, and neuroinflammatory responses, resulting in neuronal death and neurodegeneration. Several recent studies have discovered the pathogenic roles of α-Syn in traumatic and vascular central nervous system diseases, such as traumatic spinal cord injury, brain injury, and stroke, and in aggravating the processes of neurodegeneration. This review aims to highlight the structural and pathophysiological changes in α-Syn and its mechanism of action in traumatic and vascular diseases of the central nervous system.

MicroRNAs in contusion spinal cord injury: pathophysiology and clinical utility.

Spinal cord injury (SCI) in humans is a common central nervous system trauma. Pathophysiologically, SCI involves both primary and secondary damages. Therapeutically, targeting secondary damage including inflammation, neuropathic pain, apoptosis, demyelination, and glial reaction to promote functional benefits for SCI patients has long been considered a potential treatment strategy by neuroscientists and clinicians. As a type of small non-coding RNA, microRNAs (miRNAs) have been shown to play essential roles in the regulation of pathophysiologic processes of SCI and are considered to be an effective treatment method for SCI. Dysregulated expression of miRNAs is observed in SCI patients and animal models of SCI. Furthermore, miRNAs might also be used as biomarkers for diagnostic and prognostic purposes in SCI. Given contusion injury is the most clinically relevant type of SCI, this review mainly focuses on the role of miRNAs in the pathophysiology of contusion SCI and the putative utilization of miRNAs as diagnostic biomarkers and therapeutic targets for contusion SCI.