Distribution of nitric oxide synthase, nerve growth factor receptor and interstitial cells of Cajal in hirschsprung's disease and its significance

Objective To investigate the distribution of nitric oxide synthase (NOS), nerve growth factor receptor (NGFR) and interstitial cells of Cajal (ICCs) in Hirschsprung’s disease (HD). Methods The distribution of NOS, NGFR and ICCs was studied by using NADPH diaphorase histochemistry, immunohistochemistry with a monoclonal antibody to human NGFR and the specific polyclonal antibody against c-kit in 8 normal controls and 10 cases of HD. Results NOS and NGFR were abundantly present in the myenteric plexus and in the nerve fibers of musculature. ICCs were intensively distributed in the surface of circular musculature and around the myenteric plexus to form a network in normal control colon. In contrast, NOS and NGFR were scarce or absent in the myenteric plexus and in the nerve fibers of musculature, while the hypertrophic nerve trunks were NGFR positive, ICCs were scarcely distributed and the network was disrupted in the aganglionic colon in HD. Conclusion These findings suggest the involvement of NOS, NGFR and ICCs in the pathophysiology of HD.

Dorsal root ganglion progenitors differentiate to gamma-aminobutyric acid-and choline acetyltransferase-positive neurons

This study examined the isolation and differentiation of dorsal root ganglion progenitor cells for therapeutic use in neurodegenerative diseases. Rat embryonic dorsal root ganglia progenitors were isolated and purified using the differential adhesion method combined with cytosine arabinoside treatment. After culture in serum-free medium supplemented with B27, basic fibroblast growth factor and epidermal growth factor, these cells remained viable and survived for more than 18 months in vitro. Most cells differentiated to neurons that were immunoreactive for gamma-aminobutyric acid and choline acetyltransferase as detected by immunohistochemical staining. In addition, nerve growth factor and neurotrophic tyrosine kinase receptor expression were also observed in dorsal root ganglion progenitors and differentiated cells. K252a, an inhibitor that blocks nerve growth factor-induced signaling, inhibited cell survival, suggesting the possible existence of a nerve growth factor autocrine loop in these proliferating cells.

REEXPRESSION OF NERVE GROWTH FACTOR RECEPTOR IN HUMAN TRAUMATIC INJURED SPINAL CORD

In this study, the reexpression of nerve growth factor receptor (NGFR) on paraffin sections of the human spinal cord was examined with immunohistochemical method in 18 cases with survival periods of 2 hours to 28 months after trauma. The results were as follow: the reexpression of NGFR in motoneurons of the ventral horn began on the fourth day after trauma and decreased within 30 days after trauma. However, it could still be observed in patients who survived up to 28 months. The axons in funiculus dorsalis reexpressed NGFR 7 hours to 9 weeks after injury, which may be interpreted as axoplasmic transport effect of NGFR in the spinal ganglion cells. NGFR labelled intraspinal microvessels were present in the injured spinal cord. Reexpression of NGFR in motoneurons after injury reflects an increased demand of neurotrophic factors, and an increased access exerting the physiological effects of trophic factors mediated by NGFR.

Expression of nerve growth factor precursor, mature nerve growth factor and their receptors during cerebral ischemia-reperfusion injury

We investigated nerve growth factor precursor （proNGF） and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury. In both ischemic and non-ischemic cortices, proNGF was found to be present in the extracellular space and cytoplasm. In addition, mature NGF was expressed in extracellular space, but with a very low signal. In ischemic cortex only, proNGF was significantly decreased, reaching a minimal level at 1 day. Mature NGF was increased at 4 hours, then reached a minimal level at 3 days. The p75 neurotrophin receptor （p75NTR） was significantly decreased after ischemia, and increased at 3 days after ischemia. These results confirmed that proNGF was the predominant form of NGF during the pathological process of cerebral ischemia-repeffusion injury. In addition, our findings suggest that ischemic injury may influence the conversion of proNGF to mature NGF, and that proNGF/p75NTR may be involved in reperfusion injury.

Co-expression of estrogen receptor and nerve growth factor in rat intrinsic cardiac ganglia

BACKGROUND： Previous studies have shown that neurons expressing estrogen receptor and nerve growth factor exist in the intrinsic cardiac ganglia in rats. However, it remains to be shown whether estrogen receptor and nerve growth factor are co-expressed within these cells. OBJECTIVE： To determine whether estrogen receptor and nerve growth factor are co-expressed in intrinsic cardiac ganglia. DESIGN, TIME AND SETTING： This cellular morphology observational study was performed at the immunohistochemistry Department, Medicine School, Wuhan University of Science and Technology, between March and July in 2007. MATERIALS： Mouse anti-estrogen receptor and rabbit anti-nerve growth factor polyclonal antibody, biotinylated goat anti-mouse IgG, and biotinylated goat anti-rabbit IgG were provided by Wuhan Boster, China. METHODS： Ten healthy, Wistar rats were included in the present study. Ten sections of intrinsic cardiac ganglia from the atrial posterior wall were randomly selected from each rat to perform estrogen receptor and nerve growth factor double-labeling immunohistochemical staining. MAIN OUTCOME MEASURES： Expression of estrogen receptor and nerve growth factor in intrinsic cardiac ganglia of rats. RESULTS： Immunohistochemistry results demonstrated expression of estrogen receptor and nerve growth factor in rat intrinsic cardiac ganglia, and double-labeling revealed co-expression of estrogen receptor and nerve growth factor in intrinsic cardiac ganglial cells. CONCLUSION： Estrogen receptor and nerve growth factor were shown to be co-expressed in rat intrinsic cardiac ganglial cells.

Role of the nerve growth factor precursor-neurotrophin receptor p75 and sortilin pathway on apoptosis in the brain of patients with intracerebral hemorrhage

This study demonstrated that brain areas surrounding the site of hematoma following intracerebral hemorrhage are characterized by significantly increased apoptosis and expression of neurotrophin receptor p75 and sortilin. However, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemical staining, there was no significant change in nerve growth factor precursor expression levels. The appearance of neurotrophin receptor p75 expressing cells was positively correlated with cells that were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. These findings confirm that the nerve growth factor precursor-neurotrophin receptor p75-sortilin heterotrimeric complex-mediated apoptosis pathway may play an important role in cellular apoptosis following intracerebral hemorrhage.

Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

AIM:To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase(NGF-TrkA)signaling pathway and prognosis in intrahepatic cholangiocarcinoma(IHCC).METHODS:NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry.Correlations between NGF-TrkA expression and clinicopathological features were analyzed byχ2 test.Moreover,we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis.With experiments in vitro,we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-βstimulation.RESULTS:We found that NGF and TrkA expression was significantly related with differentiation(P=0.024)and intraneural invasion(P=0.003),respectively.Additionally,double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC(P=0.003).Moreover,we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion.CONCLUSION:NGF-TrkA double higher expression is an independent prognostic factor in IHCC.NGF-TrkA pathway can promote IHCC progression,indicating that NGF-TrkA may become a potential drug target.

Expression of estrogen receptor alpha,nerve growth factor,interleukin-2,and androgen receptor in the cerebellum of ovariectomized rats following soybean isoflavone treatment

BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.

Intermittent vs Continuous Administration of Nerve Growth Factor to Injured Medial Septal Cholinergic Neurons in Rat Basal Forebrain

Many medial septal neurons of the basal forebrain are dependent on nerve growth factor (NGF) from the hippocampus for survival and maintenance of a cholinergic phenotype. When deprived of their source of NGF by axotomy, medial septal neuronal cell bodies atrophy and lose their cholinergic markers. This is similar to what is observed in the basal forebrain during Alzheimer’s disease (AD). In the present study, medial septal neurons were axotomized in female rats by way of a fimbria/fornix lesion. For fourteen days following axotomy, varying NGF doses (1 - 250 μg/ml) were administered to the lateral cerebral ventricle with either mini-osmotic infusion or daily injection. The responsiveness of medial septal neurons was evaluated with choline acetyltransferase immunohistochemistry. Within the mini-osmotic pumps, NGF activity diminished greatly during the first five days of implantation, but increased dramatically in the CSF after five days of infusion. The responsiveness of medial septal neurons to NGF was dose dependent and the ED50 for NGF injection was determined to be 14.08 μg/ml compared to 27.60 μg/ml for NGF infusion. Intermittent injections at varying intervals were evaluated with 30 μg/ml NGF over a fourteen-day time period (2, 3, 6, or 12 injections). No differences occurred in the number of choline acetyltransferase neurons from rats that received weekly injections to those that received daily injections of NGF. NGF administration has been suggested as a therapy for AD. The results of these studies continue to highlight the need for NGF stability within the delivery system and AD patient CSF, the choice of delivery system, frequency of administration, and the NGF dose for maintaining basal forebrain cholinergic neurons during AD.

Role of Nerve Growth Factor (NGF) and Its Receptor Tyrosine Kinase A (TrK A) in Egyptian Cirrhotic Patients with Pruritus

Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.

Uncoupling neurotrophic function from nociception of nerve growth factor: what can be learned from a rare human disease?

Nerve growth factor(NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors contributing significantly to inflammatory pain and neuropathic pain after tissue injury. As such anti-NGF based therapies represent a promising strategy for pain management. Because of dose-dependent serious side effects such as back pain, injection site hyperalgesia, clinical trials of using NGF to treat various disorders such as diabetic neuropathies, chemotherapy-induced and human immunodeficiency virus-associated peripheral neuropathies were all discontinued. Thus far, worldwide clinical applications of NGF in treating patients are very limited except in China. Hereditary sensory autonomic neuropathy type V(HSAN V) is an extremely rare disease. Genetic analyses have revealed that HSAN V is associated with autosomal recessive mutations in NGF. One of the mutations occurred at the 100^(th) position of mature NGF resulting in a change of residue from arginine to tryptophan(R100W). Although those HSAN V patients associated with the NGF^(R100W) mutation suffer from severe loss of deep pain, bone fractures and joint destruction, interestingly patients with the NGF^(R100W) mutation do not show apparent cognitive deficits, suggesting important trophic support function is preserved. We believe that NGF^(R100W) provides an ideal tool to uncouple the two important functions of NGF: trophic versus nociceptive. Studies from investigators including ourselves have indeed confirmed in animal testing that the NGF^(R100W) no longer induced pain. More importantly, the trophic function seemed to be largely preserved in NGF harboring the R100W mutation. On the mechanistic level, we found that the NGF^(R100W) mutation was capable of binding to and signaling through the tyrosine receptor kinase A receptor. But its ability to bind to and activate the 75 kDa neurotrophic factor was significantly diminished. The significance of these findings is at least two folds: 1) the NGF^(R100W) mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management. We will discuss all the details in this mini-review.

Nerve growth factor in muscle afferent neurons of peripheral artery disease and autonomic function

In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced and exaggerate during walking,and is relieved by rest.This symptom is termed by intermittent claudication.The limb ischemia also amplifies autonomic responses during exercise.In the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses.This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle.For the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.

Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells

A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline （90 mg/kg） was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.

Vascular endothelial growth factor A promotes platelet adhesion to collagen Ⅳ and causes early brain injury after subarachnoid hemorrhage

The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.

Neurotrophic factor-based pharmacological approaches in neurological disorders

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.

Expression of NG2 and platelet-derived growth facto receptor alpha in the developing neonatal rat brain

Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.

NGF与TrkA受体在儿童膀胱过度活动症中的研究进展

神经生长因子(NGF)因其在神经细胞的存活、生长以及分化过程中发挥重要作用而得到广泛研究。它分布于机体的各处,根据所结合受体发挥不同的病理生理作用。原肌球蛋白相关激酶A(TrkA)是其高亲和力受体,诸多研究表明NGF在与其结合后,根据其下游不同的信号转导通路而发挥不同作用。NGF与其结合后还对体内发生的其他信号转导通路有交叉影响作用。本文从不同的疾病症状对NGF与TrkA结合后的信号转导通路进行综述,从而探讨NGF/TrkA信号通路在儿童膀胱过度活动症的作用。

Effect of Bushenwenyanghuayu decoction on nerve growth factor and bradykinin/bradykinin B_1 receptor in a endometriosis dysmenorrhea mouse model

OBJECTIVE:To observe the effects of Bushenwenyanghuayu decoction(BD),a Traditional Chinese Medicine(TCM),on the serum concentration of nerve growth factor(NGF) and bradykinin(BK),and protein and mRNA levels of NGF and bradykinin B_1receptor(BKB1R) in a mouse model of endometriosis dysmenorrhea.METHODS:Seventy-five experimental female BALB/c mice were randomly divided into five groups,15 mice each:sham,model,BD high dose(61.67 g/kg),BD low dose(15.42 g/kg),and gestrinone(0.4 mg/kg) groups.All the mice except for those in the sham group underwent auto-transplantation surgery and were gavaged estradiol valerate(0.5 mg/kg,daily for 12 days) after surgery.On the 12 th day,1 h after administration,writhing response was induced by intraperitoneal injection of oxytocin at 2 U/mouse.The writhing frequency and latency were recorded and the volume of the ectopic foci was measured.The concentration of serum NGF and BK was detected by enzyme-linked immunosorbent assay,the protein expression of NGF and BKB1 R was tested by immunohistochemistry and western blotting,and NGF and BKB1 R mRNAs were detected by real-time PCR.RESULTS:Compared with the model group,the volume of the ectopic foci in the treatment groups was significantly lower(P < 0.01),the writhing frequency was decreased(P < 0.05),and the writhing latency was prolonged(P < 0.01).Compared with the sham group,serum NGF and BK levels in the model group were significantly increased(P <0.01).There were positive correlations for writhing frequency among the NGF and BK groups(P <0.01).The serum NGF and BK levels were significantly lower in the treatment groups than the model group(P < 0.05).The protein expression of NGF,BKB1 R was significantly decreased in the treatment groups compared with the model group(P < 0.01).NGF and BKB1 R mRNA expression was significantly decreased in the treatment groups compared with the model group(P < 0.01).CONCLUSION:NGF and BK/BKB1 R may play an important role in the development of endometriosis-associated dysmenorrhea,and BD was found to inhibit the development of endometriosis and relieve dysmenorrhea by influencing NGF and BK/BKB1 R mRNA and protein levels.

Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves

Magnesium（Mg） wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire（3 mm diameter; 8 mm length） bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A m RNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves.