Progress of LINGO-1 in neurological diseases / 国际儿科学杂志

LINGO-1，a Nogo receptor-interacting protein-1 rich in leucine repeat sequences and immunoglobulin structural domains，which is specifically expressed in neurological diseases. In recent years，more and more evidences indicate that LINGO-1 plays an important role in glial scar formation，cell death and inflammatory reaction. LINGO-1 inhibits oligodendrocyte activation，and prevents axon and myelin formation and functional recovery，and is therefore considered to be a negative regulator of neuronal survival，neurite extension and axon myelination. The change of LINGO-1 level is related to the occurrence and development of many neurological diseases. This article reviews the physiological function of LINGO-1 and summarizes the latest research progress of LINGO-1 in multiple sclerosis，spinal cord injury，neonatal brain injury and epilepsy，so as to explore new strategies for the treatment of neurological diseases.

Advances of pathogenesis and drug development in amyotrophic lateral sclerosis / 中国药理学通报

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment / 神经科学通报·英文版

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.

Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons / 神经科学通报·英文版

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.

Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex / 神经科学通报·英文版

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.

Neuronal guidance genes in health and diseases

Neurons migrate from their birthplaces to the destinations, and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners. These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short- and long-range cell-cell communications. Neuronal guidance genes (encoding cues, receptors, or downstream signal transducers) are critical not only for development of the nervous system but also for synaptic maintenance, remodeling, and function in the adult brain. One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes, including neuronal migration, axonal guidance, synaptogenesis, and circuit formation. Importantly, neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system. We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases, ranging from developmental, neuropsychiatric, and neurodegenerative disorders to cancer metastasis. We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases. Furthermore, we discuss the remaining challenges and therapeutic potentials of modulating neuronal guidance pathways in neural repair.

Prospects from Basic Acupuncture Research to Clinical Practice / 全日本鍼灸学会雑誌

In the East, therapies such as acupuncture, moxibustion, and massage have been used to relieve pain and regulate the functions of internal organs. In these therapies, stimulation of the skin and muscles from the body surface excites somatic afferent fibers. This information is transmitted to the central nervous system, and reaches consciousness as sensations, influencing emotions and causing analgesic effects and visceral regulation via autonomic reflexes. This paper first briefly describes the characteristics of somatic-autonomic reflexes, and then introduces basic research conducted in the authors' laboratory on reflex responses to the autonomic nervous system, mainly using anesthetized animals. Finally, the authors present data from their recent olfactory research and discuss the clinical implications.

Recent progress and challenges in the treatment of spinal cord injury

Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher center and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. The pathophysiology of SCI is complicated and multifaceted, and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after SCI. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone. Although many problems and challenges remain, the encouraging outcomes that have been achieved in preclinical models offer a promising foothold for the development of novel clinical strategies to treat SCI. In this review, we characterize the mechanisms underlying axon regeneration of adult neurons and summarize recent advances in facilitating functional recovery following SCI at both the acute and chronic stages. In addition, we analyze the current status, remaining problems, and realistic challenges towards clinical translation. Finally, we consider the future of SCI treatment and provide insights into how to narrow the translational gap that currently exists between preclinical studies and clinical practice. Going forward, clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeutic benefit in humans with SCI.

Regulation of Axon Initial Segment Diameter by COUP-TFI Fine-tunes Action Potential Generation / 神经科学通报·英文版

The axon initial segment (AIS) is a specialized structure that controls neuronal excitability via action potential (AP) generation. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI (chicken ovalbumin upstream promotor-transcription factor 1) is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation. Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation, they strengthen and weaken, respectively, the receiving spontaneous network in mutant neurons. In contrast, overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation, but decreases the receiving spontaneous network. Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.

Protective effects of Slit2 on corneal epithelium and nerves in diabetic mice and its mechanism / 中华实验眼科杂志

Objective:To explore the promoting effects of slit guidance ligand 2 (Slit2) on the repair of corneal epithelium and nerve damage in diabetic mice and possible molecular mechanism.Methods:Sixty SPF C57BL/6 mice aged 5-6 weeks were divided into normal control group, diabetes model group and Slit2 injection group according to the random number table method, 20 for each group.Diabectic model was prepared by intraperitoneal injection of streptozotocin in the diabetes model group and Slit2 injection group.A mouse corneal epithelial injury repair model was established using electric epithelial scraper, and Slit2 recombinant protein was subconjunctivally injected immediately following modeling in the Slit2 injection group.The equal volume of phosphate buffer saline (PBS) was used in a same way in the diabetes model group.No intervention was performed in the normal control group.Corneal epithelial healing were examined at 24, 48 and 72 hours after corneal epithelial defect by corneal fluorescin staining.Real-time fluorescent quantitative PCR was used to detect the expression of Slit2 and its related receptors in the corneal epithelium of normal and diabetic model mice.Fluorescence staining of corneal wholemount with β-tubulin Ⅲ was used to observe the changes in corneal nerve morphology.Immunofluorescence staining was performed to detect the expression and distribution of Slit2 in mouse corneal epithelium in normal control group and diabetes model group, as well as the expression and distribution of Slit2, epidermal growth factor receptor (EGFR), extracellular-signal-regulated kinase (ERK), threonine protein kinase (AKT), β-catenin and Ki67 in the healing corneal epithelium of mice after corneal epithelium damage in different groups.The mouse corneal epithelial stem/progenitor cell line (TKE2) was divided into normal control group, high-glucose group and Slit2 treatment group.Western blot was performed to detect the expression of p-EGFR/EGFR and p-AKT/AKT in the TKE2 of the three groups.The expression of p-EGFR/EGFR and p-AKT/AKT in high glucose-cultured TKE2 with 0.01, 0.1 and 0.5 μg/ml Slit2 treatment for 10 minutes, and before and 10, 20, 30, 60, 120 minutes after 0.5 μg/ml Slit2 treatment was detected by Western blot.The effects of Slit2 on the axon regeneration of mouse trigeminal ganglion cells (TGs) were observed by immunofluorescence staining.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Qingdao Eye Hospital of Shandong First Medical University (No.[2020]57).Results:At 48 and 72 hours after corneal epithelial scraping, the speed of corneal epithelial repair was significantly slowed down in diabetes model group in comparison with the normal control group and Slit2 injection group.The relative expression levels of Slit2 and its receptors Robo1, Robo2 and Robo4 mRNA in the normal corneal epithelium in the diabetes model group were significantly higher than those of the normal control group (all at P<0.05). The fluorescence intensity of Slit2 in normal corneal epithelium in diabetes model group was similar to the normal control group, and the fluorescence intensity of Slit2 in damaged corneal epithelium in diabetic mice was significantly weaker than that in normal control group.Corneal nerve plexus was denser at 7 days after corneal epithelial injury and the nerve fibers were increased with more branches in Slit2 injection group compared with diabetic group.The fluorescence intensity of p-EGFR, p-ERK, β-catenin and Ki67 in damaged corneal epithelium in normal control group and Slit2 injection group was stronger than that of the diabetes model group.The relative expression levels of p-EGFR/EGFR, p-AKT/AKT, and β-catenin in TKE2 in high-glucose group were significantly lower than those in normal control group and Slit2 treatment group (all at P<0.05). The relative expression levels of p-EGFR/EGFR and p-AKT/AKT in high glucose-cultured TKE2 after Slit2 treatment were significantly increased in comparison with before Slit2 treatment (both at P<0.05), and the relative expression levels of p-EGFR/EGFR and p-AKT/AKT in TKE2 were elevated as the increase of Slit2 concentration.The activation effect of 0.5 μg/ml Slit2 on EGFR and AKT pathways was most obvious.The synapse length of TGs cultured by high glucose was (40.52±5.44) μm, which was significantly shortened than (72.14±9.48) μm in normal control group and (73.04±4.66) μm in Slit2 injection group (both at P<0.05). Conclusions:Slit2 can protect the corneal epithelium by activating EGFR signaling pathway and play a protective role to neurons by increasing the density of corneal subepithelial plexus and promoting the growth of TGs axons in diabetic mice.

The role of p75 neurotrophin receptor in neurodegenerative diseases / 中国药理学通报

Recently p75 neurotrophin receptor (p75NTR) has been found to play a critical role in the pathology of neurodegen¬erative! diseases including Alzheimer's disease (AD) , Parkin¬son' s disease ( PI)), Huntington's disease ( HI)) , amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).This arti¬cle reviews the research progress of p75NTR in regulating neuron apoptosis, axon degeneration and cognitive impairment, explo¬ring the application of p75NTR as a potential therapeutic target for the treatment of neurodegenerative diseases.

Protective effect and mechanism of ginsenoside Rb1 on repairing sciatic nerve injury in mice / 解剖学报

Objective To explore the effect and mechanism of ginsenoside Rb1 on the repair of sciatic nerve injury (SNI) in mice. Methods Seventy-eight adult male Kunming mice were randomly divided into sham group (26), SNI group (26), SNI+Rb1 group (26). The SNI+Rb1 group was given 10 mg/kg ginsenoside Rb1 (i.p.), and the SNI group and the sham group were given the same volume of normal saline. The injury method was established by squeezing the sciatic nerve. Sciatic functional index (SFI) was used to evaluate sciatic nerve function. Growth associated protein 43 (GAP43) immunofluorescent staining was used to detect neural regeneration and repair on day 14, and the structure changes of the myelin sheath of the injured segment were observed under transmission electron microscope. Ki67 and S100β were used to detect the proliferation and migration ability of Schwann cells, and Real-time PCR was used to detect the mRNA expression levels after crush on day 3 and day 7. Results SFI of SNI+Rb1 group was higher than SNI group. The HE result showed that the sciatic nerve was uniform in the SNI + Rb1 group. The result of immunofluorescent staining displayed that Rb1 enhanced GAP43

Ultrastructural clarification of the peripherally located actin network in the myelinated axons / Aclaración ultraestructural de la red de actina localizada periféricamente en los axones mielinizados

SUMMARY: Despite the existence of a large amount of actin in the axons, the concentration F-actin was quite low in the myelinated axons and almost all the F-actin were located in the peripheries of the myelinated axons. Until now, the ultrastructural localization of F-actin has still not been reported in the myelinated axons, probably due to the lack of an appropriate detection method. In the present study, a phalloidin-based FITC-anti-FITC technique was adopted to investigate the subcellular localization of F-actin in the myelinated axons. By using this technique, F-actin is located in the outer and inner collars of myelinated cytoplasm surrounding the intermodal axon, the Schmidt-Lanterman incisures, the paranodal terminal loops and the nodal microvilli. In addition, the satellite cell envelope, which encapsulates the axonal initial segment of the peripheral sensory neuron, was also demonstrated as an F-actin-enriched structure. This study provided a hitherto unreported ultrastructural view of the F-actin in the myelinated axons, which may assist in understanding the unique organization of axonal actin cytoskeleton.

RESUMEN: A pesar de la existencia de una gran cantidad de actina en los axones, la concentración de F-actina era bastante baja en los axones mielinizados y casi la totalidad de F-actina se localizaba en las periferias de los axones mielinizados. A la fecha aún no se ha reportado la localización ultraestructural de F-actina en los axones mielinizados, probablemente debido a la falta de un método de detección apropiado. En el presente estudio, se adoptó una técnica FITC-anti-FITC basada en faloidina para investigar la localización subcelular de F-actina en los axones mielinizados. Mediante el uso de esta técnica, la F-actina se localiza en los collares externo e interno del citoplasma mielinizado que rodea el axón intermodal, a las incisiones de Schmidt-Lanterman,a las asas terminales paranodales y a las microvellosidades nodales. Además, la envoltura de la célula satélite, que encapsula el segmento axonal inicial de la neurona sensorial periférica, también se demostró como una estructura enriquecida con F-actina. Este estudio proporcionó una vista ultraestructural de la F-actina en los axones mielinizados, que puede ayudar a comprender la organización única del citoesqueleto de actina axonal.

Advance of Netrin-1 for Protection and Repairment of Injuries after Cerebral Infarction (review) / 中国康复理论与实践

Netrin-1 may protect and repair the damage caused by cerebral infarction, in terms of inhibiting apoptosis and inflammatory, and promoting angiogenesis and axon regeneration, etc. Netrin-1 may associate with the pathogenesis and outcome of cerebral infarction. The application of Netrin-1 in clinic needs more researches.

Research progress on dental pulp stem cells in the repair of peripheral nerve injury / 口腔疾病防治

@#Peripheral nerve injury (PNI) is a common disease in the oral cavity that can easily lead to loss of function and abnormal appearance. The application of dental pulp stem cells (DPSCs) combined with tissue engineering in the repair of PNI is a research hotspot. DPSCs have the advantages of abundant sources, simple extraction, low immunogenicity and a high proliferation rate in vitro. They can differentiate into Schwann cells (SCs). SCs can induce autophagy and secrete key neurotrophic factors, such as nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor and glial cell-derived neurotrophic factor. SCs are beneficial for the repair of nerve injury. DPSCs in different periods have differences in immune regulation, anti-inflammatory effects, expression of neural markers, angiogenesis and so on, which provide more diversified choices for nerve repair. At present, the introduction of tissue engineering provides a more controllable and improved microenvironment for DPSCs, which is conducive to the application and development of DPSCs in regenerative medicine and tissue engineering. However, there are still many problems to be solved, such as the selection of stem cells, functional link recovery, uncontrollable direction of axon regeneration, regulation of the peripheral nervous system and mechanism of repair.

The effect of rehabilitation training on the expression of neuroglobin in the peri-infarct cortex and its mechanism / 中华物理医学与康复杂志

Objective:To study the effect of rehabilitation training on the expression of neuroglobin (Ngb), oxidative stress and axon regeneration in the cortex and explore possible mechanisms of functional recovery after cerebral infarction.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group, a model group and a rehabilitation group. Cerebral infarction was modelled in the model and rehabilitation groups using Longa′s middle cerebral artery occlusion (MCAO) technique. The sham operation group received the same procedure except that no thread was inserted to block the middle cerebral artery. The rats in the rehabilitation group began treadmill training 24h after the operation, while the other two groups were left on the treadmill without training. On the 3rd, 7th and 14th days after the operation, all of the rats′ neurological functioning was assessed using modified neurological severity scores (mNSSs). After the last mNSS test, all of the rats were sacrificed and peri-infarct brain tissue was resected to detect the expression of Ngb and oxidative stress indicators including superoxide dismutase (SOD), nitric oxide and malondialdehyde (MDA), as well as neurofilament-200 (NF-200) indicating axon regeneration.Results:On the 3rd day after the surgery there was no significant difference between the average mNSS scores of the rehabilitation and model groups. On the 7th and 14th day the average mNSS score of the rehabilitation group was significantly better than that of the model group. The average expression of Ngb in the model group was significantly higher than in the sham operation group. After the intervention, the average expression of SOD in the rehabilitation group was significantly higher than in the model group, while NO and MDA expression were significantly lower. After the intervention the average expression of NF-200 in the rehabilitation group was also significantly higher than in the model group.Conclusions:Rehabilitation training benefits the recovery of neurological function after cerebral infarction, at least in rats. The mechanism may be related to the upregulation of Ngb, alleviation of oxidative stress and enhancement of axonal regeneration in the peri-infarct cortex.

Improvement of bladder function and repair of axonal injury in rats with traumatic spinal cord injury via MAPK/ERK pathway by nerve growth factor / 西安交通大学学报(医学版)

【Objective】 To explore the effects of nerve growth factor （NGF） on bladder function and axon injury repair in rats with traumatic spinal cord injury （t-SCI） so as to explore its molecular mechanism. 【Methods】 Traumatic spinal cord injury model was constructed in 30 male SD rats by modified Allen’s beating method. The rats were randomly divided into sham-operation group， injury group and NGF group， with 10 rats in each group. We used the BBB score to observe the motor function of the rats’ hind limbs before and after the operation. The BL-420 biometer experimental system detected the urodynamics. Six anterior roots of the left lumbar taken from the distal end of the anastomosis were stained with toluidine blue， and the number of myelinated axons was counted. We used HE to stain rat bladder tissue， TUNEL to stain the rats’ severely injured spinal cord， and observed the spinal cord apoptosis rate. Western blotting was used to detect the protein expressions of Raf-1， p-MEK-2， MEK-2， ERK1/2， and p-ERK1/2 in spinal cord tissue. 【Results】 The BBB score results showed that there was no difference in the scores of the sham-operation group， the injury group and the NGF group before the operation. After the operation， the scores of the injury group and the NGF group were significantly lower than those in the sham-operation group （P0.05）. 【Conclusion】 NGF may hinder the conduction of MAPK/ERK pathway， thereby affecting the repair of axon damage and improving the bladder function of t-SCI rats.

Axonal cytomechanics in neuronal development

For more than a century, mechanical forces have been predicted to govern many biological processes duringdevelopment, both at the cellular level and in tissue homeostasis. The cytomechanics of the thin and highlyextended neuronal axons have intrigued generations of biologists and biophysicists. However, our knowledgeof the biophysics of neurite growth and development is far from complete. Due to its motile behavior and itsimportance in axonal pathfinding, the growth cone has received significant attention. A considerable amount ofinformation is now available on the spatiotemporal regulation of biochemical signaling and remodeling of thegrowth cone cytoskeleton. However, the cytoskeletal organization and dynamics in the axonal shaft werepoorly explored until recently. Driven by advances in microscopy, there has been a surge of interest in theaxonal cytoskeleton in the last few years. A major emerging area of investigation is the relationship betweenthe axonal cytoskeleton and the diverse mechanobiological responses of neurons. This review attempts tosummarize our current understanding of the axonal cytoskeleton and its critical role in governing axonalmechanics in the context of neuronal development.

Effect of Buyang Huanwu Tang on Axonal Regeneration of Rats After Ischemic Stroke Injury / 中国实验方剂学杂志

Objective:To investigate the effects of Buyang Huanwu Tang （BHT） on axonal regeneration and neurological rehabilitation of the rats suffering ischemic stroke （IS）. Method:A total of 180 SD rats were used to establish a middle cerebral artery infarction （MCAO） model. The animals that were successfully modeled were randomly divided into model group， BHT group （12 g·kg-1） and nimodipine group （20 mg·kg-1）， and a sham group was established， with 28 rats in each group. After seven-days intragastric administration of BHT， the animals were sacrificed. TTC staining was used to test cerebral infarction. Brain water content was measured to observe cerebral edema. Bielschowsky's silver staining and immunofluorescence were performed to observe axonal degeneration and the protein expression of neurofilament protein-200（NF-200）. Quantitative real-time polymerase chain reaction （PCR） was used to analyze the mRNA expression of repulsion oriented molecule a （RGMa）， Ras homologous enzyme （Rho）， Rho kinase （ROCK）， and collapsion response regulatory protein 2 （CRMP2）. Neurological function scores assay was used to examine neurological recovery. Result:Compared with sham group， the cerebral infarction volume and brain water content increased significantly（P<0.01）， and motor function was markablely decreased in the model group. Axonal degeneration and nerve fiber damage were obviously observed. Also， gene expression of axon growth-related protein was deviation from normal （P<0.01）. Compared with model group， the cerebral infarction rate （P<0.01）， brain water content （P<0.01） and axonal degeneration of BHT group and nimodipine group were significantly reduced. The expression of NF-200 was increased. Also， the mRNA expression of RGMa， Rho and ROCK was lower （P<0.05） while the mRNA expression of CRMP2 was higher （P<0.01）. And the neurological function was significantly improved （P<0.05）. Conclusion:BHT can promote axon regeneration after ischemic stroke injury by regulating the mRNA expression of axon growth-related protein， thereby improving nerve function.

Progress on axon regeneration in model organisms / 浙江大学学报·医学版

Different from neurons in the peripheral nervous system, mature neurons in the mammalian central nervous system often fail to regenerate after injury. Recent studies have found that calcium transduction, injury signaling, mitochondrial transportation, cytoskeletal remodeling and protein synthesis play essential roles in axon regeneration. Firstly, axon injury increases the intracellular concentration of calcium, and initiates the injury signaling pathways including cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and dual leucine kinase (DLK), which are found to promote axon regeneration in multiple animal injury models. The second step for axonal regrowth is to rebuild growth cones. Overexpressing proteins that promote dynamics of microtubules and actin filaments is beneficial for the reassembly of cytoskeletons and initiation of new growth cones. Thirdly, mitochondria, the power factory for cells, also play important roles in growth cone formation and axonal extension. The last but not the least important step is the regulation of gene transcription and protein translation to sustain the regrowth of axons. This review summarizes important findings revealing the functions and mechanisms of these biological progresses.