• The Journal of Internal Korean Medicine
• /
• v.30 no.4
• /
• pp.674-684
• /
• 2009

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes a physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. This study was undertaken to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression were measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size had decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GF AP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of a rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.

• Journal of Korean Medicine Rehabilitation
• /
• v.21 no.2
• /
• pp.143-158
• /
• 2011

Objectives : Peripheral nerve injuries are commonly encountered clinical problem and often result in severe functional deficits. The aim of this study is to evaluate the effects of aqueous extract of Achyranthes japonica(AJ) on functional recovery in sciatic nerve after crushed sciatic nerve injury. Methods : In the present study, the animals in the AJ-treated groups received the aqueous extract of AJ at the respective doses orally for 13 consecutive days. In order to assess the effects of the aqueous extract of AJ on function recovery in crushed sciatic nerve injury, sciatic functional index(SFI) was performed. c-Fos expression in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG), and neurofilament, and the expressions of brain-derived neurotrophic factor(BDNF), nerve growth factor(NGF) following crushed sciatic nerve injury in rats were investigated. For this, immunohistochemistry and western blot were performed. Results : In the present study, crushed sciatic nerve injury showed characteristic gait changes showing decrease of SFI value and treatment with the aqueous extract of AJ significantly enhanced the SFI value. Neurofilament expression in the sciatic nerve was decreased by crushed sciatic nerve injury and treatment with the AJ increased neurofilament expression. The expressions of BDNF and NGF in the sciatic nerve were increased following crushed sciatic nerve injury and treatment with the AJ significantly controlled the sciatic nerve injury-induced increment of BDNF and NGF expressions. c-Fos expressions in the PVN and vIPAG were increased following crushed sciatic nerve injury and treatment with the AJ significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions. Conclusions : These results suggest that AJ treatment after crushed sciatic nerve injury is effective in the functional recovery by enhancing axonal regeneration and suppressing of pain.

• The Korean Journal of Pain
• /
• v.14 no.1
• /
• pp.83-92
• /
• 2001

Background: This study was undertaken to observe the functional changes of the hind limb and histopathological changes in the sciatic nerve after an injection of alcohol or phenol, which are commonly used neurolytic agents, highlighting the time of recovery. Methods: Forty-eight Sprague-Dawley rats weighing 200-300 g were used for the experiment. Histopathological changes under the electron microscope, were observed in the distal part of the sciatic nerve, into which 0.1 ml of alcohol or phenol was injected. This was severed in 3 rats of each group at 10 minutes, 1 hour, 24 hours, 3 days, 1, 2, 4 and 6 weeks later. The functional changes in the hind limbs were observed for 6 weeks by noting their walking pattern. Results: Following the injection of alcohol or phenol into the right sciatic nerve, the right hind limb showed a severe pronounced motor weakness and obvious gait changes. About 2 weeks later, gradual improvement of gait changes began, and after 6 weeks, the motor weakness and gait changes were no longer perceptible in both groups. The findings of any histopathological change were similar in both alcohol or phenol groups. At 10 minutes after injection, destructive lesions were confined to the unmyelinated fibers and the myelin sheath of small the myelinated fibers. On the 3rd day and at 1 week, pathologic changes in axonal fibers and Schwann cells were in being phagocytized in spite of myelin restitution. From 2 to 4 weeks, axonal regeneration and remyelination appeared at the same time a myelin disintegration and axonolysis. At 6 weeks, neural regeneration was similar to that of the contralateral control group. Conclusions: These results suggest that functional and histopathological changes, after injection of neurolytics into the peripheral nerves, are quite similar in both alcohol and phenol groups. The progression of functional and histopathological changes become more obvious according to the time interval following the injection. Consequently, side effects that develop following the use of alcohol or phenol may begin to improve around the time that nerve regeneration occurs, i.e., two to four weeks later.

• Archives of Plastic Surgery
• /
• v.33 no.2
• /
• pp.213-218
• /
• 2006

As the large defect of peripheral nerve occurs, the autologous nerve graft is the most ideal method but it has many limitations due to donor site morbidities. Various materials have been developed for the nerve defect as the conduits, but none of these materials is satisfactory. Among them, $Gore-Tex^{(R)}$ tube seems to be one of the most ideal nerve conduit materials at peripheral nerve defect. Many researches have focused on finding the neurotrophic factors. It is recently demonstrated that Valproic acid(VPA) has an effect of axonal regeneration as a neurotrophic factor without enzymatic degradation and toxicity problems. The purpose of this study is to evaluate the effect of VPA on the nerve regeneration at the peripheral nerve defect. A 10 mm gap of rat sciatic nerve was made and $Gore-Tex^{(R)}$ tube filled with biceps femoris muscle was placed at the nerve defect site. We let the rat take VPA as drinking water in experimental group and did not give VPA to the control group. We estimated the results as electrophysiologic and histological aspects for 16 weeks after the surgery. The nerve conduction velocity, total myelinated axon count, myelin sheath thickness and mean nerve fiber diameter significantly increased in VPA-treated experimental group when compared to the control (p < 0.05). From the above results, we conclude that VPA promotes the nerve regeneration at the peripheral nerve defect site. It is suggested that $Gore-Tex^{(R)}$ tube filled with skeletal muscle and VPA administration may be a good substitute for autologous nerve graft.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
• /
• v.11 no.2
• /
• pp.172-177
• /
• 2000

Background and Objectives : Until now, various attempts have been made fir reinnervating paralyzed vocal cord. Nevertheless, the most cases did not produce satisfactory outcome due to occurrence of synkinesis of larynx secondary to misdirected axonal regeneration. Accordingly, the purpose of this investigation is to learn the effect of chronic electrical stimulation on regeneration of the recurrent laryngeal nerve. Material and Methods : Using 20 healthy male Sprague-Dawley rats(250-300g) with normal vocal functions, transections were made on their left recurrent laryngeal nerves and then primary anastomosis were performed under the operating microscope and they were divided into an experimental group and a control group each having 10 rats. After the procedure, for the experimental group, chronic electrical stimulation was carried out until vocal cord movement was functionally recovered. for the control group, only chronic electrical stimulation was not given. Result : In experimental group, the number of functionally recovered rats was two and in control group, that of functionally recovered rate was same. The reorganization of posterior cricoarytenoid muscle motoneuron in nucleus ambiguus appeared in the case of directed reinnervation of recurrent laryngeal nerve. Conclusion : The chronic electrical stimulation does not a direct beneficial effect on the early functional recovery in rats with injured recurrent laryngeal nerve.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.17 no.4
• /
• pp.317-330
• /
• 1995

The purpose of this study is to observe the stimulant effect of the isolated nerve segment on the peripheral nerve regeneration using silicone tube in rats. Sprague-Dawley female albino rats were used as experimental animals and nerve defects were made by resection of 14 mm-long segment of right sciatic nerves. In control group, the defects were bridged with the silicone tubes. In experimental group, the defects were bridged with the same manner and additionally, 2mm-long nerve segments were inserted at the center of the silicone tubes. 3 months later, the regenerated nerve tissue within the silicone tubes were examined by histologic study. Axonal diameters and numbers of axons were measured and all data were analyzed by using SAS package program. The results obtained were as follows : 1. The experimental group was increased than the control group in general diameters of the regenerated nerve fiber.(P<0.05) 2. The diameters of axons were increased in the experimental group compare to the control group.(P<0.05) 3. The numbers of axons were increased in the experimental group compare to the control group.(P<0.05)

• The Korean Journal of Physiology and Pharmacology
• /
• v.10 no.3
• /
• pp.111-121
• /
• 2006

Neuroprotective properties of lithium were evaluated by using in vivo NMDA excitotoxicity model. Systemic injection of NMDA to young mice induced neuronal apoptosis mediated by both TNFR-l and Fas ligand, and long-term lithium treatment showed noticeable neuroprotection against NMDA-induced excitotoxicity: NMDA-damaged neurons expressed several apoptosis-related gene products such as TNFR-l, Fas ligand, and caspase-3, and these gene expressions were not found in the brain of mice chronically treated with lithium. Therefore, it is highly likely that the protection offered by chronic lithium treatment occurred at far upstream of caspase activation, since the chronic lithium treatment increased the expression of Bcl-2, an important antiapoptotic gene known to act upstream of caspase cascade. Timm's histochemistry indicated the complete blockade of the NMDA insults by the treatment. There was no indication of axonal regeneration, which follows synaptic degeneration induced by neuronal damage. Furthermore, this study reports for the first time that TNFR-l and Fas ligand are involved in neuroprotective effects of lithium in NMDA-induced neuronal apoptosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.32 no.4
• /
• pp.295-307
• /
• 2006

Styela clava, called non-native tunicate or sea squirt, is habitat which include bays and harbors in Korea and several sites in the sea faced world. We fabricate cellulose membrane nerve conduit (CMNC) from this native sea squirt skin, and evaluate the capacity of promoting peripheral nerve regeneration in the rat sciatic nerve defect model. After processing the pure cellulose membrane from the sea squirt skin as we already published before, CMNC was designed as a non-tubular sheet with 14 mm length and 4 mm width. Total eleven male Spraque-Dawley rats (12 weeks, weighing 250 to 300g) were divided into sham group (n=2), silicone tube grafted control group (n=3) and experimental group (n=6). Each CMNC grafted nerve was evaluated after 4, 8 and 12 weeks in the experimental group, and after 12 weeks, sciatic function was evaluated with sciatic function index (SFI) and gait analysis, and histomorphology of nerve conduit and the innervated tissues of sciatic nerve were all examined using image analyzer and electromicroscopic methods in the all groups. The regenerated axon and nerve sheath were found only in the inner surface of the CMNC after 4 weeks and became more thicker after 8 and 12 weeks. In the TEM study, CMNC grafted group showed more abundant organized myelinated nerve fibers with thickened extracellular matrix than silicone conduit grafted group after 12 weeks. The sciatic function index (SFI) and ankle stance angle (ASA) in the functional evaluation were $-47.2{\pm}3.9$, $35.5^{\circ}{\pm}4.9^{\circ}$ in CMNC grafted group (n=2) and $-80.4{\pm}7.4$, $29.2^{\circ}{\pm}5.3^{\circ}$ in silicone conduit grafted group (n=3), respectively. And the myelinated axon was 41.59% in CMNC group and 9.51% in silicone conduit group to the sham group. The development of a bioactive CMNC to replace autogenous nerve grafts offers a potential and available approach to improved peripheral nerve regeneration. As we already published before, small peptide fragment derived from the basement membrane matrix proteins of squirt skin, which is a kind of anchoring protein composed of glycocalyx, induced the effective axonal regeneration with rapid growth of Schwann cells beneath the inner surface of CMNC. So the possibilities of clinical application as a peripheral nerve regeneration will be able to be suggested.

• The Journal of Internal Korean Medicine
• /
• v.31 no.4
• /
• pp.763-774
• /
• 2010

Objectives : In condition of brain infarction, irreversible axon damage occurs in central nerve system(CNS), because gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study is to examine the effect of the Uncariae Ramulus et Uncus on CD81 and GFAP expression in the rat brain following middle cerebral artery occlusion. Methods : In order to study ischemic injuries on brain, infarction was induced by middle cerebral artery occlusion(MCAO) using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Results : The following results were obtained 1. Measuring the size of cerebral infartion induced by MCAO in the rat after injection of Uncariae Ramulus et Uncus showed the size was decreased. 2. Intravenous injection of Uncariae Ramulus et Uncus showed pyramidal cell death protection in the hippocampus in the MCAO rat. 3. Water extract injection of Uncariae Ramulus et Uncus decreased GFAP expression significantly in the MCAO rat. 4. Uncariae Ramulus et Uncus water extract decreased CD81 expression in the MCAO rat. 5. The administration of water extract of Uncariae Ramulus et Uncus induced up-regulation of c-Fos expression significantly compared with MCAO. 6. The admistration of water extract of Uncariae Ramulus et Uncus increased ERK expression significantly compared with MCAO. Conclusion : We observed that Uncariae Ramulus et Uncus could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infaction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the up-regulation of c-Fos and ERK. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

• The Journal of Korean Medicine
• /
• v.29 no.1
• /
• pp.167-178
• /
• 2008

Object : Gliosis becomes a physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by hypoxic brain injury is involved with up-regulation of CD81 and GFAP. The current study was to examine the effect of the Angelica Sinens on CD81 and GFAP regulation after hypoxic brain injury in the astrocyte. Methods : MTT assay was performed to examine cell viability, and cell based ELISA, western blot and PCR were used to detect the expression of CD81 and GFAP. Results : The following results were obtained: 1. Using ELISA, western blot and PCR from the astrocyte after hypoxic injury, CD81 and GFAP expression was seen to have increased. 2. After the administration of Angelica Sinens extract to astrocyte following hypoxic injury, CD81 and GFAP expression was down regulated significantly. The water extract of Angelica Sinens prevented cell destruction by hypoxic induced with $CoCl_2$. Conclusion : These results indicate that Angelica Sinens could suppress reactive gliosis, which disturbs astrocyte regeneration after hypoxic brain injury by controlling the expression of CD81 and GFAP.