Effect of Suanzaoren Tang Combined with Ziwu Liuzhu Acupuncture on Vertebral Artery Hemodynamics， Inflammatory Cytokines， and Neurotrophic Factors in Patients with Cervical Insomnia / 中国实验方剂学杂志

ObjectiveTo explore the effect of Suanzaoren Tang combined with Ziwu Liuzhu acupuncture on the vertebral artery hemodynamics， inflammatory cytokines， and neurotrophic factors in the patients with cervical insomnia with syndrome of deficiency of both heart and spleen. MethodThe random number table method was employed to assign 164 patients with cervical insomnia with syndrome of deficiency of both heart and spleen treated in the First Clinical Medical School of Guangzhou University of Chinese Medicine from January 2018 to June 2021 into a control group and an observation group. The control group was orally administrated with 1-2 mg estazolam tablets before bed for 4 weeks， and the observation group with Suanzaoren Tang combined with Ziwu Liuzhu acupuncture for 4 weeks. The therapeutic efficacy and safety were observed. The Pittsburgh Sleep Quality Index （PSQI） score， polysomnography monitoring results， hemodynamics parameters of vertebral artery， and serum levels of inflammatory cytokines and neurotrophic factors were compared before and after treatment. ResultExcept 4 dropouts， the remaining 160 patients were included in this study， with 80 patients in each group. The observation group had higher total effective rate than the control group ［92.50% （74/80） vs. 80.00% （64/80）， χ2=5.270， P<0.05］. Compared with that before treatment， the therapies in both groups decreased the PSQI score， sleep latency time， awakening time， awakening times， serum levels of interleukin-1β （IL-1β）， C-reactive protein （CRP）， and tumor necrosis factor-α （TNF-α） （P<0.01）. Meanwhile， they increased the proportion of rapid-eye-movement （REM） sleep， the diastolic blood flow velocity （Vd）， systolic blood flow velocity （Vs）， and mean blood flow velocity （MFV） of vertebral artery， as well as the serum levels of brain-derived neurotrophic factor （BDNF） and glial cell-derived neurotrophic factor （GDNF） （P<0.05， P<0.01）. Moreover， the observation group had lower PSQI score， sleep latency time， awakening time， awakening times， and serum IL-1β， CRP， and TNF-α levels （P<0.01） and higher proportion of REM sleep， Vd， Vs， MFV of vertebral artery， and serum BDNF and GDNF levels （P<0.05， P<0.01） than the control group. ConclusionZiwu Liuzhu acupuncture combined with Suanzaoren Tang can improve blood circulation of vertebral artery， reduce the serum levels of inflammatory cytokine， and increase the serum levels of neurotrophic factors to improve the sleep quality of the patients with cervical insomnia with syndrome of deficiency of both heart and spleen.

Effect of Suanzaoren Tang Combined with Ziwu Liuzhu Acupuncture on Vertebral Artery Hemodynamics， Inflammatory Cytokines， and Neurotrophic Factors in Patients with Cervical Insomnia / 中国实验方剂学杂志

ObjectiveTo explore the effect of Suanzaoren Tang combined with Ziwu Liuzhu acupuncture on the vertebral artery hemodynamics， inflammatory cytokines， and neurotrophic factors in the patients with cervical insomnia with syndrome of deficiency of both heart and spleen. MethodThe random number table method was employed to assign 164 patients with cervical insomnia with syndrome of deficiency of both heart and spleen treated in the First Clinical Medical School of Guangzhou University of Chinese Medicine from January 2018 to June 2021 into a control group and an observation group. The control group was orally administrated with 1-2 mg estazolam tablets before bed for 4 weeks， and the observation group with Suanzaoren Tang combined with Ziwu Liuzhu acupuncture for 4 weeks. The therapeutic efficacy and safety were observed. The Pittsburgh Sleep Quality Index （PSQI） score， polysomnography monitoring results， hemodynamics parameters of vertebral artery， and serum levels of inflammatory cytokines and neurotrophic factors were compared before and after treatment. ResultExcept 4 dropouts， the remaining 160 patients were included in this study， with 80 patients in each group. The observation group had higher total effective rate than the control group ［92.50% （74/80） vs. 80.00% （64/80）， χ2=5.270， P<0.05］. Compared with that before treatment， the therapies in both groups decreased the PSQI score， sleep latency time， awakening time， awakening times， serum levels of interleukin-1β （IL-1β）， C-reactive protein （CRP）， and tumor necrosis factor-α （TNF-α） （P<0.01）. Meanwhile， they increased the proportion of rapid-eye-movement （REM） sleep， the diastolic blood flow velocity （Vd）， systolic blood flow velocity （Vs）， and mean blood flow velocity （MFV） of vertebral artery， as well as the serum levels of brain-derived neurotrophic factor （BDNF） and glial cell-derived neurotrophic factor （GDNF） （P<0.05， P<0.01）. Moreover， the observation group had lower PSQI score， sleep latency time， awakening time， awakening times， and serum IL-1β， CRP， and TNF-α levels （P<0.01） and higher proportion of REM sleep， Vd， Vs， MFV of vertebral artery， and serum BDNF and GDNF levels （P<0.05， P<0.01） than the control group. ConclusionZiwu Liuzhu acupuncture combined with Suanzaoren Tang can improve blood circulation of vertebral artery， reduce the serum levels of inflammatory cytokine， and increase the serum levels of neurotrophic factors to improve the sleep quality of the patients with cervical insomnia with syndrome of deficiency of both heart and spleen.

The effects of mechanical vibration on the expression of estrogen and brain-derived neurotrophic factor after ovariectomy / 中华物理医学与康复杂志

Objective:To explore any effect of mechanical vibration on the expression of estrogen and brain-derived neurotrophic factor (BDNF) in ovariectomized rats with an osteoporotic fracture.Methods:Thirty 3-month-old female Wistar rats were divided randomly into a control group, an ovariectomy group and a vibration group, each of 10. Fractures were induced in the rats of all three groups. Twenty minutes of whole-body vertical vibration was applied to the vibration group at a frequency of 35Hz, 5 days a week for 6 weeks. After 2 and 6 weeks the fracture healing of each group was evaluated using X-rays, the levels of hippocampal estrogen were measured using enzyme-linked immunosorbent assays and fracture-end BDNF was quantified by immunoblotting.Results:After 2 and 6 weeks of vibration the average fracture healing in the vibration group was significantly greater than in the other 2 groups. The average estrogen content in the hippocampus of the vibration group was significantly higher than in the other 2 groups after both 2 and 6 weeks, while the average BDNF content in their fracture ends was significantly lower. The BDNF expression at the fracture end was significantly correlated with the fracture healing.Conclusion:Mechanical vibration can promote the expression of estrogen and BDNF in the hippocampus and accelerate fracture healing in osteoporotic rats.

Absence of an association between serum interleukin-6 and brain-derived neurotrophic factor in drug-naïve first-episode major depression

ABSTRACT Peripheral and central cytokine interleukin-6 (IL-6) levels play an important role in the pathophysiology of major depression (MD). We investigated the association between serum levels of IL-6 and brain-derived neurotrophic factor (BDNF) in drug-naïve, first-episode patients with MD. This study included 28 patients (male/female: 11/17; mean [standard deviation] age, 46.7 [11.9] years) who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for MD without any physical diseases. We evaluated the severity of depression using the Hamilton Rating Scale for Depression. No associations were found between serum levels of IL-6 and BDNF (r=-0.102, P =0.605). These results suggest that IL-6 does not influence BDNF and vice versa, but both act in a peripheral manner.

Vitamin D3 Attenuates Type 3 Diabetic-Associated Cognitive Deficits in Rats through Regulating Neurotrophins and Enhancing Cholinergic Transmission Pathway

Objective: To examine the protective effect of Vitamin D3 against Type 3 diabetes-induced cognitive dysfunction in rats. Materials and Methods: Type 3 diabetes was induced by a high-fat diet plus streptozotocin in rats. Rats were divided into seven groups: negative control, positive control, Vitamin D3 groups (100, 500 and 1000 IU/kg/day), Vitamin D3 plus rivastigmine, and rivastigmine monotherapy. A radial arm maze test was used to assess cognitive function. Levels of acetylcholinesterase (AChE), dopamine (DA), nerve growth factor, neurotrophin-3 (NT-3), and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus were estimated by the enzyme-linked immunosorbent assay kits. Results: Chronic treatment with Vitamin D3 significantly (P < 0.05) and dose dependently alleviated cognitive deficits, with enhancing cholinergic transmission pathway activity through attenuated hippocampal AChE and increased DA level (P < 0.001). Moreover, Vitamin D3 significantly increased (P < 0.001) neurotrophin levels as an underlying mechanism for the resulted improvement. Conclusion: Vitamin D3 plus rivastigmine (combined group) is better than Vitamin D (100 and 500 mg/kg/day) for improvement of AChE, DA, NT-3, and GDNF levels. Vitamin D (500 and 1000 IU/kg/day) was effective as a combined group in terms of the behavioral test.

Effect of Zhongfeng Xingnao Liquid on Neurological Recovery of Patients with Ischemic Stroke at Early Recovery / 中国实验方剂学杂志

<b>Objective::To discuss the effect of Zhongfeng Xingnao liquid on neurological recovery of patients of ischemic stroke with Qi deficiency and blood stasis syndrome at early recovery, and the mechanisms of anti-inflammation, neuroprotection and improvement of microcirculation. <b>Method::One hundred and twenty-eight patients were randomly divided into control group (64 cases) and observation group (64 cases) by random number table. Both groups’ patients got atorvastatin, 10 mg/days, aspirin enteric-coated tablets, 100 mg/days, and control of blood pressure and blood sugar, and modern rehabilitation training. Patients in control group orally got Zhongfeng Xingnao liquid, 25 mL/time, 3 times/days. The course of treatment was 90 days. And before and after treatment, national institutes of health neurological deficiency (NIHSS), Barthel index, improvement Rankin scale, brunel balance scale (BBA), Fugl-Meyer scale (FMA), Qi deficiency and blood stasis syndrome (SS-QOL) were scored. And levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha), homocysteine (Hcy), serum cystatin C (Cys-C), platelet aggregation rate (ADP) and fibrinogen (FIB) were detected. <b>Result::The clinical efficacy in observation group was better than that in control group (<italic>Z</italic>=1.981, <italic>P</italic><0.05). At different time points after treatment, scores of NIHSS and Qi deficiency and blood stasis syndrome were lower than those in control group (<italic>P</italic><0.05), whereas scores of Barthel index, FMA, BBA and SS-QOL were higher than those in control group (<italic>P</italic><0.01). Degrees of disability and dyskinesia in observation group was lighter than those in control group (<italic>Z</italic>=1.932, <italic>P</italic><0.05). Degree of dyskinesia was lighter than that in control group (<italic>Z</italic>=2.149, <italic>P</italic><0.05). And level of BDNF was higher than that in control group (<italic>P</italic><0.01), while levels of TNF-<italic>α</italic>, Hcy, Cys-C, ADP and FIB were lower than those in control group (<italic>P</italic><0.01). <b>Conclusion::In addition to the routine comprehensive rehabilitation measures of western medicine, Zhongfeng Xingnao liquid can promote recovery of nerve function defect of patients of cerebral infarction with Qi deficiency and blood stasis syndrome at convalescence, is beneficial for rehabilitation of patients and improving the quality of life, with certain effects in resisting inflammation, improving microcirculation and protecting nerves, and better efficacy than simple western medicine treatment.

Effect of Jiajian Fuyuan Huoxuetang Combined with Electroacupuncture on Neurological Rehabilitation After Spinal Cord Injury / 中国实验方剂学杂志

Objective:To observe the effect of Jiajian Fuyuan Huoxuetang combined with electroacupuncture on neurological rehabilitation of patients with spinal cord injury, and to investigate its effect on neurotrophic and inflammatory factors. Method:One hundred and twenty patients were randomly divided into control group (59 cases) and observation group (61 cases) by random number table. Both groups’ patients got monosialotetrahexosylganglioside by intravenous drip for 6 weeks, 200-400 mg/time, 1 time/day.Rat nerve growth factor for injection by intramuscular injection for 4 weeks, 20 μg/time, 1 time/day. Patients in control group additionally got electroacupuncture treatment,and tongluo huatan capsule,3 caps/time,3 time/days. The patients in observation group additionally got Jiajian Fuyuan Huoxuetang combined with electroacupuncture, 1 dose/day. The courses of treatment were 12 weeks in two groups. Scores of degree of spinal cord neurological impairment were graded by using impairment score of American Spinal Injury Association (ASIA). Lower extremity motor ability was discussed by using the walking index of spinal cord injuryⅡ (WISCⅠ Ⅱ) and 10 minutes’ walking time (10 MWT). Before and after treatment, functions of daily life were evaluated by using Barthel index (MBI). Bladder function was also discussed, and levels of brain-derived nerve growth factor in peripheral blood (BDNF), nerve growth factor (NGF), astrogenic calcium binding protein S-100 β (S-100 β), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also detected. Result:After the treatment, scores of sensory and motor in ASIA scale in observation group were all higher than those in control group (P<0.01). Score of WISCⅠ Ⅱ in observation group was higher than that in control group, and 10 MWT was shorter than that in control group (P<0.01). Times of leakage of urine, urinary incontinence volume and residual urine volume were all less than those in control group, and bladder volume was more than that in control group (P<0.01). Functions of daily life in observation group were better than those in control group (Z=1.967, P<0.05), and the levels of BDNF and NGF were higher than those in control group, while levels of S-100 β, TNF-α and IL-1β were lower than those in control group (P<0.01). Conclusion:On the basis of routine comprehensive rehabilitation therapy of western medicine, Jiajian Fuyuan Huoxuetang combined with electroacupuncture can promote the recovery of nervous function, improve sensory and motor function, improve bladder function and daily living ability, and promote the expression of neurotrophic factors and inhibit inflammatory reaction in neurological rehabilitation for the patients with spinal cord injury.

Effects of Endogenous Neurotrophic Factors on Nerve Regeneration after Cryopreserved Sciatic Nerve Allograft in Rats / 中国康复理论与实践

Objective:To investigate the effect of endogenous neurotrophic factor (ENTFs) on nerve regeneration after cryopreserved sciatic nerve allograft in rats. Methods:The 15-mm sciatic nerves from female Sprague-Dawley rats were placed in DMEM solution and pretreated in vitro for 1 day, 3 days, 7 days, 14 days, and 21 days at 37 ℃ with 5% CO2 (groups A, B, C, D and E) respectively. Fresh nerve group (group F) was set up. The protein expression of glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), Bcl-2, Bax, Caspase-3, major histocompatibility complex (MHC)-I and MHC-II was detected by Western blotting. The above six groups were cryopreserved in liquid nitrogen for four weeks. The living cells and dead cells of the nerves after cryopreservation were observed by Calcein-AM/propidium iodide staining. In addition, the above six cryopreserved groups and another fresh nerve group (group G) were transplanted to the Wistar rats by allografting (groups A', B', C', D', E', F' and G'). Isograft group (group H') was set up. One week after transplantation, the expression of CD8+ T cells and macrophages of the graft were observed by immunofluorescence staining, and the plasma levels of interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were detected by ELISA. Twenty weeks after transplantation, the compound muscle action potential (CMAP) and nerve conduction velocity (NCV) were examined by electrophysiology. The wet weight ratio of gastrocnemius muscle was calculated by the operational side compared with the contralateral side. The expression of neurofilament protein (NF) 200 of the transplanted nerves was observed by immunofluorescence staining. The number of myelinated nerve fibers was analyzed by toluidine blue staining. The thickness of myelinated was analyzed by electron microscopy. Results:Compared with group F, the protein expression of GDNF and NGF increased in groups C, D and E (P < 0.05); the protein expression of Bcl-2 reduced and the protein expression of Bax and Caspase-3 increased in groups B, C, D, and E (P < 0.05); the protein expression of MHC-I and MHC-II decreased in all the pretreated groups (P < 0.05). Four weeks after cryopreservation, compared with groups F and G, the number of living cells decreased in groups C, D and E. One week after transplantation, compared with groups F' and G', the expression of CD8+ T cells and macrophages decreased, and the plasma concentration of IL-2 and TNF-α decreased in groups C', D' and E' (P<0.05). Twenty weeks after transplantation, CMAP, NCV, the wet weight ratio of gastrocnemius muscle, the number of axon and thickness of myelin sheath were better in groups C', D' and E' than in groups F' and G' (P<0.05), as well as the expression of NF200. Conclusion:ENTFs can be induced by pretreating the sciatic nerve in vitro. Cryopreserved sciatic nerve with high expression of ENTFs could promote nerve regeneration and functional recovery after allograft.

Low-intensity pulsed ultrasound for regenerating peripheral nerves: Potential for penile nerve / 亚洲男科学杂志(英文版)

Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.

Effects of transplanting BDNF overexpressed neural stem cells on neurotrophic factor induction hippocampus after radiation exposure / 中华放射医学与防护杂志

Objective To evaluate the effects of neural stem cells (NSCs) overexpressing brainderived neurotrophic factor (BDNF) on the levels of neurotrophic factors and microglia activation in hippocampus after brain irradiation.Methods Hippocampal NSCs were isolated from fetal rat brain and infected with GFP-lentivirus and GFP-BDNF-lentivirus.SD rats were randomized into four groups:control group,irradiated group (R group),GFP-modified NSCs transplantation group with irradiation (R+NSCs group),and GFP-BDNF modified NSCs transplantation group with irradiation (R+BDNF-NSCs group).NSCs were transplanted into the bilateral hippocampus of rats one month after whole brain irradiation at a single dose of 20 Gy.The expressions of BDNF,glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in hippocampus were detected at 2 and 8 weeks after transplantation.The activation of microglia was observed by immunofluorescence.Results At 2 and 8 weeks after transplantation,the expressions of BDNF and NGF proteins in hippocampus of R+BDNF-NSCs group were significantly higher than those of R group (P＜0.05).The activated microglia in the R+NSCs group and the R+BDNF-NSCs group had no decrease compared with R group (P＞ 0.05).Conclusions The transplantation of NSCs overexpressing BDNF promotes the production of BDNF and NGF,which improves the level of neurotrophic factors in hippocampus after radiation.

Effects of donepezil on the expression of neurotrophic related factors in subventricular zone of cerebral infarction mice / 中华行为医学与脑科学杂志

Objective To investigate the effect of donepezil on subventricular zone ( SVZ) neuro-genesis related neurotrophic factors after cerebral infarction. Methods Mice were randomly assigned into three groups: vehicle-treated sham group (Sham+vehicle,n=18),vehicle-treated middle cerebral artery oc-clusion (MCAO) group (MCAO + vehicle,n=30) and donepezil-treated MCAO group (MCAO+donepezil, n=30). Middle cerebral artery occlusion( MCAO) was induced by thread-occlusion method. Nissl staining was used to measure the infarct volume and the modified neurological severity score(mNSS) was used to as-sess neurologic function and brain water content was detected to assess brain edema degree. Proliferative cells and neuroblasts were labeled with 5-bromodeoxyuridine ( BrdU) and doublecortin ( DCX). The SVZ BrdU+/DCX+cells were detected by immunofluorescence. The expression of glial cell line-derived neurotro-phic factor (GDNF),brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detec-ted by Western blot. Results The infarct volume of MCAO + donepezil group ((13. 33±4. 55)%) was sig-nificantly lower than that of MCAO + vehicle group ((31. 33±3. 93)%,t=7. 34,P<0. 05). The neurologic deficits were significantly ameliorated after donepezil treatment,and the brain water content of MCAO + done-pezil group ((71. 82±10. 18)%)was significantly less than that of MCAO + vehicle group ((85. 93± 7. 54)%,F=13. 480,P<0. 05). All differences were statistically significant (P<0. 05). The area of BrdU+/DCX+cells within SVZ of MCAO + vehicle group ((6. 16±1. 79)%) was significantly larger than that of sham + vehicle group ((2. 25±1. 09)%),and was fewer than that of MCAO+donepezil group ((16. 19± 2. 16)%,F=102. 756,P<0. 05). MCAO significantly promoted the expression of GDNF,BDNF and NGF within SVZ compared with sham operation,and donepezil increased these protein levels(F=15. 114,27. 121, 27. 398,P<0. 05). Conclusion Donepezil regulates neurogenesis via increasesing the expression of GDNF, BDNF and NGF within SVZ after cerebral infarction.

Research status of neuronal-glial cell symbiosis system on neurotrophic factor activity / 眼科新进展

Retinitis pigmentosa is characterized by the progressive loss of the structure and function of photoreceptors and retinal pigment epithelium.Neurotrophic factors are more and more concerned.Brain-derived neurotrophic factors,ciliary neurotrophic factors and glial cell line-derived neurotrophic factors can affect photoreceptor activity through direct and indirect protection pathways.Neuronal-glial cell symbiosis system mediated by the indirect protection of photoreceptors is more important.Studies on glial cell-mediated neurotrophic factors for the treatment of related eye disease have made some progress,which will provide a new and effective methodsto delay the development of RP.

Latest progress in stem cell transplantation for the treatment of optic nerve injury / 眼科新进展

Injury or death of retinal ganglion cells may lead to irreversibly damage to visual function.However,no treatment have showed efficiency to replace the damaged cells and restore the visual function.Due to the multi-directionally differentiated potential of stem cells,their role in optic nerve protection and restoration following injury is becoming a hot research spot.The purpose of this article is to summarize the progress of stem cells for the repair of optic nerve in basic and clinical researches.

Neuroprotective effect of fasudil combined with bone marrow-derived neural stem cells on mice with experimental autoimmune encephalomyelitis / 中国病理生理杂志

AIM: To explore the neuroprotective effect of fasudil combined with bone marrow -derived neural stem cells ( BM-NSCs) on the mice with experimental autoimmune encephalomyelitis ( EAE).METHODS: Female C57BL/6 mice (8~10 weeks old, n=32) were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish chronic EAE model .The mice were randomly divided into control ( ddH2 O ) group, fasudil group , BM-NSCs group , and fasudil+BM-NSCs group .The clinical score and body weight were recorded every other day .The expression of neurotrophic factors was determined by immunofluorescence staining .RESULTS:In comparison with ddH2O group, fasud-il combined with BM-NSCs delayed onset and ameliorated severity of EAE .The numbers of brain-derived neurotrophic fac-tor, glial cell-derived neurotrophic factor , nerve growth factor , neurotrophin-3 and ciliary neurotrophic factor positive cells in fasudil group, BM-NSCs group and fasudil +BM-NSCs group were all increased in various extents .In particularly, the expression of these neurotrophic factors in fasudil +BM-NSCs group was significantly higher than that in the mice treated with fasudil or BM-NSCs alone (P<0.01).CONCLUSION:Fasudil combined with BM-NSCs promotes the expression of neurotrophic factors and improves microenvironment of central nervous system , thus playing a positive role in neural restora-tion and regeneration through a synergistic and superimposed effect .

Recent advances in neurotrophic factors promoting corneal epithelial wound healing / 眼科新进展

Neurotrophic factors are a species of protein molecules,which produced by tissue supplied by nerve and astrocytes and necessary for neuronal growth and survival.Neurotrophic factors play an important role in the development and physiological function of the nervous system.It can promote neurons growth and development,and keep neurons functional integrity.Except for the regulation and functionality action on the innervated tissue,neurotrophic factors play an important neurotrophic role for the tissue physiology,growth and metabolism.The cornea is the highest density of nerve fibers.Abundant nerve fibers enhance the sensory function.In addition,the nerve fibers can also secrete various nutrition and regulatory factors to keep the physiological function and regeneration.In recent years,the research of neurotrophic factors on promoting corneal epithelial wound healing has made great progress.This article reviews the recent advances in different neurotrophic factors promoting the repair of corneal epithelial injury.

Expressions of miRNAs related to accelerating senescence in serum of patients with amnestic mild cognitive impairment and analysis on their biological information / 吉林大学学报(医学版)

Objective:To explore the expressions of miRNAs related to accelerating senescence in serum of the patients with amnestic mild cognitive impairment (aMCI), and to clarify their effects in the pathogenesis of aMIC.Methods:The levels of miRNAs related to accelerating senescence (miR-132, miR-193b, miR-130b, miR-20a, miR-296, miR-329 and miR-206) were measured in the serum of the patients with aMCI (aMCI group,n=66) and healthy controls(control group,n=76) using quantitative real-time PCR(qRT-PCR).The genes targeted by the altered miRNAs were predicted by TargetScan 6.0.DAVID was used to analyze the function of miRNA target genes.The serum levels of brain derived neurotrophic factor (BDNF) and silent in formation regulator 1(SIRT1) were measured by enzyme-linked immunosorbent assay (ELISA) method.Results:The expression levels of miR-206 and miR-132 in serum of the patients in aMCI group were significantly higher than those in control group (P<0.05).BDNF and SIRT1 were both target genes of miR-206 and miR-132.The levels of BDNF (29.50 μg·L-1± 3.13 μg·L-1) and SIRT1 (1.86 μg·L-1± 0.25 μg·L-1) in serum of the patients in aMCI group were both obviously lower than those in control group (BDNF: 32.29 μg·L-1±3.66 μg·L-1;SIRT1: 2.10 μg·L-1± 0.29 μg·L-1, P<0.05).Conclusion:The expression levels of miR-206 and miR-132 in serum of the aMCI patients are significantly up-regulated.Both of them might be involved in the pathogenesis of aMCI through inhibiting the BDNF and SIRT1 expressions.

Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients / Níveis séricos de adiponectina, CCL3/MIP-1α, and CCL5/RANTES discriminam pacientes com migrânea e cefaleia do tipo tensional

ABSTRACT Objectives Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. Methods This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. Results We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. Conclusions This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.

RESUMO Objetivos Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional. Métodos Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados. Resultados Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia. Conclusões Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional, sugerindo papeis distintos destas moléculas na fisiopatologia destas duas cefaleias primárias.

Inflammatory mediators of neuropathic pain / Mediadores inflamatórios na dor neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Pro-inflammatory chemical mediators and algogenic substances seem to be confused by the sharing of their actions and by interactions in painful and inflammatory presentation. This study aimed at presenting a review of major inflammatory chemical mediators and place them in neuropathic pain pathophysiology. CONTENTS: Inflammation is the homeostatic response of vascularized tissues to remove harmful agents and restore their normal functions. Nervous system (central and/or peripheral) diseases and injuries may induce neuropathic pain and may also modify inflammatory process nervous mediation. In such pathological conditions, there might be pain without restrict link with admitedly harmful or painful stimuli, as well as there might be inflammation without restrict link with the presence of harmful agents and the need to remove them. Chemical mediators involved in neuropathic pain and inflammation pathophysiology modulate the presentation of both. CONCLUSION: Studies on inflammation offer evidences to support the important role of their chemical mediators in neuropathic pain pathogenesis. In peripheral and central sensitization, a thin borderline between reversibility or not of neuropathic pain may be respected or exceeded by inflammatory mediators actions.

RESUMO JUSTIFICATIVA E OBJETIVOS: Mediadores químicos pró-inflamatórios e substâncias algogênicas parecem se confundir pelo compartilhamento de suas ações e pelas interações no quadro doloroso e inflamatório. O objetivo deste estudo foi apresentar uma revisão sobre os principais mediadores químicos inflamatórios e situá-los na fisiopatologia da dor neuropática. CONTEÚDO: A inflamação é a resposta homeostática de tecidos vascularizados no sentido de remoção de agentes lesivos e restauro de suas funções normais. Doenças e lesões no sistema nervoso (central e/ou periférico) podem causar dor neuropática, e, também modificar a mediação nervosa do processo inflamatório. Nessas condições patológicas a dor pode ocorrer sem o vínculo restrito com estímulo reconhecidamente nocivo ou doloroso, assim como ocorrer quadro inflamatório sem o vínculo restrito com a presença de agentes lesivos e a necessidade de removê-los. Os mediadores químicos envolvidos na fisiopatologia da dor neuropática e da inflamação modulam o quadro de ambas. CONCLUSÃO: Os estudos sobre inflamação oferecem evidências para embasar a importância do papel dos seus mediadores químicos na patogênese da dor neuropática. Na sensibilização periférica e, também na central uma fronteira tênue entre a reversibilidade ou não do quadro neuropático pode ser respeitada ou ultrapassada pelas ações de mediadores inflamatórios.

Neurotrophic factors in tension-type headache / Fatores neurotróficos na cefaleia do tipo tensional

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Os fatores neurotróficos (FN) participam da regulação da dor e podem ter um papel na fisiopatologia das cefaleias peimárias. O objetivo do presente estudo foi avaliar os níveis séricos de FN em pacientes com cefaleia do tipo tensional (CTT). Foi realizado corte transversal com 48 pacientes com CTT e 48 controles pareados por gênero e idade. Os inventários de Beck para depressão e ansiedade, bem como o inventário de impacto da cefaleia foram aplicados. Os níveis séricos de FN foram determinados por ELISA. Não houve diferenças significativas entre níveis de FN entre pacientes com TTH e controles, bem como entre pacientes com TTH episódica e crônica. Presença de cefaleia no momento da avaliação não alterou os níveis séricos de FN. Os escores de depressão, ansiedade e impacto da cefaleia não se correlacionaram com os níveis de FN. Nosso estudo sugere que não há alteração dos níveis de FN na TTH.

Biomarkers and staging of bipolar disorder: a systematic review / Dos biomarcadores ao estadiamento do transtorno bipolar: uma revisão sistemática

INTRODUCTION: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages. METHODS: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder. RESULTS: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers. CONCLUSIONS: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression. .

INTRODUÇÃO: Níveis crescentes de evidência sugerem que o transtorno bipolar (TB) exibe um caráter progressivo, em nível tanto clínico, quanto bioquímico e neuroimagiológico. Este estudo revisa a literatura existente sobre a relação entre biomarcadores específicos e estágios do TB. MÉTODOS: Uma busca extensa da literatura nas bases de dados MEDLINE e PubMed foi conduzida para identificar estudos publicados em inglês e em português utilizando as palavras-chave biomarker (biomarcador), neurotrophic factors (fatores neurotróficos), inflammation (inflamação), oxidative stress (estresse oxidativo), neuroprogression (neuroprogressão) e staging models (modelos de estadiamento), em referência cruzada com o termo bipolar disorder (transtorno bipolar). RESULTADOS: Estudos morfométricos em doentes bipolares mostraram a existência de alterações neuroanatômicas, tais como o alargamento dos ventrículos, a perda de substância cinzenta no hipocampo e no cerebelo, a diminuição do volume de determinadas áreas do córtex pré-frontal e variações no tamanho da amígdala. Além disso, outros estudos apontam para a potencialidade do uso dos valores séricos dos fatores neurotróficos, de mediadores inflamatórios e de estresse oxidativo como biomarcadores do TB. CONCLUSÕES: O conhecimento das alterações neurobiológicas, associadas à progressão e atividade do TB, é fundamental para a identificação de biomarcadores. A incorporação de biomarcadores nos modelos de estadiamento do TB poderá permitir um aperfeiçoamento dos algoritmos terapêuticos, possibilitando a elaboração de esquemas de tratamento mais personalizados e eficazes, com destaque para a importância da intervenção precoce na atenuação da progressão da doença. .