Restorative Mechanism of Neural Progenitor Cells Overexpressing Arginine Decarboxylase Genes Following Ischemic Injury

Cell replacement therapy using neural progenitor cells (NPCs) following ischemic stroke is a promising potential therapeutic strategy, but lacks efficacy for human central nervous system (CNS) therapeutics. In a previous in vitro study, we reported that the overexpression of human arginine decarboxylase (ADC) genes by a retroviral plasmid vector promoted the neuronal differentiation of mouse NPCs. In the present study, we focused on the cellular mechanism underlying cell proliferation and differentiation following ischemic injury, and the therapeutic feasibility of NPCs overexpressing ADC genes (ADC-NPCs) following ischemic stroke. To mimic cerebral ischemia in vitro , we subjected the NPCs to oxygen-glucose deprivation (OGD). The overexpressing ADC-NPCs were differentiated by neural lineage, which was related to excessive intracellular calcium-mediated cell cycle arrest and phosphorylation in the ERK1/2, CREB, and STAT1 signaling cascade following ischemic injury. Moreover, the ADC-NPCs were able to resist mitochondrial membrane potential collapse in the increasingly excessive intracellular calcium environment. Subsequently, transplanted ADC-NPCs suppressed infarct volume, and promoted neural differentiation, synapse formation, and motor behavior performance in an in vivo tMCAO rat model. The results suggest that ADC-NPCs are potentially useful for cell replacement therapy following ischemic stroke.

M2 Phenotype Microglia-derived Cytokine Stimulates Proliferation and Neuronal Differentiation of Endogenous Stem Cells in Ischemic Brain

Microglia play a key role in the immune response and inflammatory reaction that occurs in response to ischemic stroke. Activated microglia promote neuronal damage or protection in injured brain tissue. Extracellular signals polarize the microglia towards the M1/M2 phenotype. The M1/M2 phenotype microglia released pro- and anti-inflammatory cytokines which induce the activation of neural stem/progenitor cells (NSPCs). In this study, we investigated how the cytokines released by microglia affect the activation of NSPCs. First, we treated BV2 cells with a lipopolysaccharide (LPS; 20 ng/ml) for M1 phenotype microglia and interleukin-4 (IL-4; 20 ng/ml) for M2 phenotype microglia in BV2 cells. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h. In ex vivo, brain sections containing the subventricular zone (SVZ) were cultured in conditioned media of M1 and M2 phenotype-conditioned media for 3 d. We measured the expression of cytokines in the conditioned media by RT-PCR and ELISA. The M2 phenotype microglia-conditioned media led to the proliferation and neural differentiation of NSPCs in the ipsilateral SVZ after ischemic stroke. The RT-PCR and ELISA results showed that the expression of TGF-α mRNA was significantly higher in the M2 phenotype microglia-conditioned media. These data support that M2 phenotype microglia-derived TGF-α is one of the key factors to enhance proliferation and neural differntiation of NSPCs after ischemic stroke.

Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

Ischemic preconditioning (IP) is one of the most important endogenous mechanisms that protect the cells against ischemia-reperfusion (I/R) injury. However, the exact molecular mechanisms remain unclear. In this study, we showed that changes in the level of agmatine were correlated with ischemic tolerance. Changes in brain edema, infarct volume, level of agmatine, and expression of arginine decarboxylase (ADC) and nitric oxide synthases (NOS; inducible NOS [iNOS] and neural NOS [nNOS]) were analyzed during I/R injury with or without IP in the rat brain. After cerebral ischemia, brain edema and infarct volume were significantly reduced in the IP group. The level of agmatine was increased before and during ischemic injury and remained elevated in the early reperfusion phase in the IP group compared to the experimental control (EC) group. During IP, the level of plasma agmatine was increased in the early phase of IP, but that of liver agmatine was abruptly decreased. However, the level of agmatine was definitely increased in the ipsilateral and contralateral hemisphere of brain during the IP. IP also increased the expression of ADC—the enzyme responsible for the synthesis of endogenous agmatine—before, during, and after ischemic injury. In addition, ischemic injury increased endogenous ADC expression in the EC group. The expression of nNOS was reduced in the I/R injured brain in the IP group. These results suggest that endogenous increased agmatine may be a component of the ischemic tolerance response that is induced by IP. Agmatine may have a pivotal role in endogenous ischemic tolerance.

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-kappaB (NF-kappaB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-kappaB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.

Glutathione Protects Brain Endothelial Cells from Hydrogen Peroxide-Induced Oxidative Stress by Increasing Nrf2 Expression

Glutathione (GSH) protects cells against oxidative stress by playing an antioxidant role. Protecting brain endothelial cells under oxidative stress is key to treating cerebrovascular diseases and neurodegenerative diseases including Alzheimer's disease and Huntington's disease. In present study, we investigated the protective effect of GSH on brain endothelial cells against hydrogen peroxide (H2O2). We showed that GSH attenuates H2O2-induced production of nitric oxide (NO), reactive oxygen species (ROS), and 8-Oxo-2'-deoxyguanosine (8-OHdG), an oxidized form of deoxiguanosine. GSH also prevents H2O2-induced reduction of tight junction proteins. Finally, GSH increases the level of nuclear factor erythroid 2-related factor 2 (Nrf2) and activates Nrf2-mediated signaling pathways. Thus, GSH is a promising target to protect brain endothelial cells in conditions of brain injury and disease.

TRPV1 Activation in Primary Cortical Neurons Induces Calcium-Dependent Programmed Cell Death

Transient receptor potential cation channel, subfamily V, member 1 (TRPV1, also known as vanilloid receptor 1) is a receptor that detects capsaicin, a pungent component of chili peppers, and noxious heat. Although its function in the primary nociceptor as a pain receptor is well established, whether TRPV1 is expressed in the brain is still under debate. In this study, the responses of primary cortical neurons were investigated. Here, we report that 1) capsaicin induces caspase-3-dependent programmed cell death, which coincides with increased production of nitric oxide and peroxynitrite ; that 2) the prolonged capsaicin treatment induces a steady increase in the degree of capase-3 activation, which is prevented by the removal of capsaicin; 3) and that blocking calcium entry and calcium-mediated signaling prevents capsaicin-induced cell death. These results indicate that cortical neurons express TRPV1 whose prolonged activation causes cell death.

The Effect of Agmatine on Expression of IL-1beta and TLX Which Promotes Neuronal Differentiation in Lipopolysaccharide-Treated Neural Progenitors

Differentiation of neural progenitor cells (NPCs) is important for protecting neural cells and brain tissue during inflammation. Interleukin-1 beta (IL-1beta) is the most common pro- inflammatory cytokine in brain inflammation, and increased IL-1beta levels can decrease the proliferation of NPCs. We aimed to investigate whether agmatine (Agm), a primary polyamine that protects neural cells, could trigger differentiation of NPCs by activating IL-1beta in vitro. The cortex of ICR mouse embryos (E14) was dissociated to culture NPCs. NPCs were stimulated by lipopolysaccharide (LPS). After 6 days, protein expression of stem cell markers and differentiation signal factors was confirmed by using western blot analysis. Also, immunocytochemistry was used to confirm the cell fate. Agm treatment activated NPC differentiation significantly more than in the control group, which was evident by the increased expression of a neuronal marker, MAP2, in the LPS-induced, Agm-treated group. Differentiation of LPS-induced, Agm-treated NPCs was regulated by the MAPK pathway and is thought to be related to IL-1beta activation and decreased expression of TLX, a transcription factor that regulates NPC differentiation. Our results reveal that Agm can promote NPC differentiation to neural stem cells by modulating IL-1beta expression under inflammatory condition, and they suggest that Agm may be a novel therapeutic strategy for neuroinflammatory diseases.

Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell differentiation after ischemic brain injury

Neural stem cells (NSCs) have been suggested as a groundbreaking solution for stroke patients because they have the potential for self-renewal and differentiation into neurons. The differentiation of NSCs into neurons is integral for increasing the therapeutic efficiency of NSCs during inflammation. Apoptosis signal-regulating kinase 1 (ASK1) is preferentially activated by oxidative stress and inflammation, which is the fundamental pathology of brain damage in stroke. ASK1 may be involved in the early inflammation response after stroke and may be related to the differentiation of NSCs because of the relationship between ASK1 and the p38 mitogen-activated protein kinase pathway. Therefore, we investigated whether ASK1 is linked to the differentiation of NSCs under the context of inflammation. On the basis of the results of a microarray analysis, we performed the following experiments: western blot analysis to confirm ASK1, DCX, MAP2, phospho-p38 expression; fluorescence-activated cell sorting assay to estimate cell death; and immunocytochemistry to visualize and confirm the differentiation of cells in brain tissue. Neurosphere size and cell survival were highly maintained in ASK1-suppressed, lipopolysaccharide (LPS)-treated brains compared with only LPS-treated brains. The number of positive cells for MAP2, a neuronal marker, was lower in the ASK1-suppressed group than in the control group. According to our microarray data, phospho-p38 expression was inversely linked to ASK1 suppression, and our immunohistochemistry data showed that slight upregulation of ASK1 by LPS promoted the differentiation of endogenous, neuronal stem cells into neurons, but highly increased ASK1 levels after cerebral ischemic damage led to high levels of cell death. We conclude that ASK1 is regulated in response to the early inflammation phase and regulates the differentiation of NSCs after inflammatory-inducing events, such as ischemic stroke.

Expression of transient receptor potential channels in the ependymal cells of the developing rat brain / 대한해부학회지

Cerebrospinal fluid (CSF) plays an important role in providing brain tissue with a stable internal environment as well as in absorbing mechanical and thermal stresses. From its initial composition, derived from the amniotic fluid trapped by the closure of neuropores, CSF is modified by developing and differentiating ependymal cells lining the ventricular surface or forming the choroid plexus. Its osmolarity and ionic composition brings about a change through the action of many channels expressed on the ependymal cells. Some newly discovered transient receptor potential (TRP) channels are known to be expressed in the choroid plexus ependyma. To detect additional TRP channel expression, immunohistochemical screening was performed at the choroid plexus of 13-, 15-, 17-, and 19-day embryos, using antibodies against TRPV1, TRPV3, and TRPA1, and the expression was compared with those in the adult TRP channels. The level of TRP channel expression was higher in the choroid plexus which suggests more active functioning of TRP channels in the developing choroid plexus than the ventricular lining ependyma in the 15- and 17-day embryos. All the expression of TRP channels decreased at the 19th day of gestation. TRPA1 was expressed at a higher level than TRPV1 and TRPV3 in almost all stages in both the choroid plexus and ventricular lining epithelium. The highest level of TRPV1 and TRPV3 expression was observed in association with the glycogen deposits in the cytoplasm of the choroid plexus ependymal cells of the 15- and 17-day embryos.

Overexpression of Human Arginine Decarboxylase Rescues Human Mesenchymal Stem Cells against H2O2 Toxicity through Cell Survival Protein Activation

In this study, we explored the potentiality of human arginine decarboxylase (ADC) to enhance the survival of mesenchymal stem cells (MSCs) against unfavorable milieu of host tissues as the low survival of MSCs is the issue in cell transplantation therapy. To address this, human MSCs overexpressing human ADC were treated with H2O2 and the resultant intracellular events were examined. First, we examined whether human ADC is overexpressed in human MSCs. Then, we investigated cell survival or death related events. We found that the overexpression of human ADC increases formazan production and reduces caspase 3 activation and the numbers of FITC, hoechst, or propidium iodide positive cells in human MSCs exposed to H2O2. To elucidate the factors underlying these phenomena, AKT, CREB, and BDNF were examined. We found that the overexpression of human ADC phosphorylates AKT and CREB and increases BDNF level in human MSCs exposed to H2O2. The changes of these proteins are possibly relevant to the elevation of agmatine. Collectively, our data demonstrate that the overexpression of human ADC stimulates pro-survival factors to protect human MSCs against H2O2 toxicity. In conclusion, the present findings support that ADC can enhance the survival of MSCs against hostile environment of host tissues.

Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain / 대한해부학회지

Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) plays a protective role in cerebral ischemia by maintaining vascular permeability, whereas NO derived from neuronal and inducible NOS is neurotoxic and can participate in neuronal damage occurring in ischemia. Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane if brain vessels to promote cell death and tissue injury. We previously reported that agmatine, synthesized from L-arginine by arginine decarboxylase (ADC) which is expressed in endothelial cells, has shown a direct increased eNOS expression and decreased MMPs expression in bEnd3 cells. But, there are few reports about the regulation of eNOS by agmatine in ischemic animal model. In the present study, we examined the expression of eNOS and MMPs by agmatine treatment after transient global ischemia in vivo. Global ischemia was induced with four vessel occlusion (4-VO) and agmatine (100 mg/kg) was administered intraperitoneally at the onset of reperfusion. The animals were euthanized at 6 and 24 hours after global ischemia and prepared for other analysis. Global ischemia led severe neuronal damage in the rat hippocampus and cerebral cortex, but agmatine treatment protected neurons from ischemic injury. Moreover, the level and expression of eNOS was increased by agmatine treatment, whereas inducible NOS (iNOS) and MMP-9 protein expressions were decreased in the brain. These results suggest that agmatine protects microvessels in the brain by activation eNOS as well as reduces extracellular matrix degradation during the early phase of ischemic insult.

Agmatine Attenuates Nitric Oxide Synthesis and Protects ER-structure from Global Cerebral Ischemia in Rats / 대한해부학회지

In ischemic strokes, apoptosis is caused by excitotoxicity, ionic imbalance, oxidative/nitrosative stress, and apoptotic-like pathways. Nitric oxide (NO), a free radical, is elevated after ischemic insult. NO, which is generated primarily by neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), promotes neuronal damage following ischemia. Evidence obtained in recent years has demonstrated that endoplasmic reticulum (ER)-mediated cell death plays an important role in cerebral ischemia. Agmatine is an endogenous substance synthesized from L-arginine by arginine decarboxylase (ADC) and is present in mammalian brain. We had previously reported that agmatine contributes to neuroprotection against ischemic injury. In continuation of our earlier work, we intended to investigate whether agmatine protects brain from transient global ischemia, and also tried to determine the neuroprotective mechanism of agmatine. Twenty minutes of transient global ischemia was induced by 4 vessel occlusion (4-VO). Agmatine (100 mg/kg, IP) was administered simultaneously with reperfusion. Samplings of brain were done at 6, 24, 48, and 72 h after reperfusion to determine the effect of agmatine on ischemic injured hippocampus. ER-damage was also investigated using electron microscope. Results showed that agmatine treatment prevented delayed neuronal cell death in hippocampal CA1 neurons after global cerebral ischemia. It also blocked NOS expression in the rat brain. Agmatine induced the increased expression of glucose-regulated protein 78 (Grp78). These results suggest that agmatine inhibits the production of NO by decreasing the expression of nNOS and iNOS on global forebrain ischemia and the neuroprotective effect of agmatine were concerned with the ER stress-mediated condition.

The Effect of Agmatine on Expression of MMP2 and MMP9 in Cerebral Ischemia / 대한해부학회지

Agmatine is a primary amine formed by decarboxylation of L-arginine synthesized in the mammalian brain. Recent studies have shown that agmatine is neuroprotective in models of trauma and ischemia. The purpose of this study was to evaluate the effect of agmatine on the expression of MMP2 and MMP9, which are expressed in reperfusion injury following cerebral ischemia. Mice were subjected to 2 h middle cerebral artery occlusion and 22 h reperfusion. Agmatine (100 mg/kg) was administered intraperitoneally at the start of reperfusion. Agmatine treatment significantly reduced the immunoreactivity of MMP2 and MMP9 in the cortex, striatum, and penumbra on the ipsilateral side. The immunoreactivity of MMP2 and MMP9 was markedly lower in blood vessels of the agmatine-treated group than in the experimental control group. Immunoblot analysis showed that agmatine treatment decreased the expression of MMP2 and MMP9. After exogenous agmatine administration, the expression of agmatine was higher in the striatum and penumbra of the agmatine-treated group than in the experimental control group. The fluorescence intensity was markedly greater in blood vessels in the agmatine-treated group than in the experimental control group. These data suggest that agmatine might decrease the expression of MMP2 and MMP9 by regulating NOS activity, and thereby modulating NO synthesis.

Human Papilloma Virus Type 16 E7 Oncoprotein Stabilizes p53 Protein but not Induced p53-mediated Apoptosis in HepG2 Cells after gamma-irradiation under Hypoxia / 대한해부학회지

Human papilloma virus 16 E6 and E7 oncoproteins are well known to change cell functions, especially through p53 and pRb expression, so we studied their effects on molecular mechanisms and on the cell death associated with hypoxia and ionizing radiation. These treatments both caused cell death and increased p53 protein expression in HepG2 cells. This increased p53 expression by gamma-irradiation under hypoxia induced G1 cell cycle arrest and led to apoptosis even though HepG2 cells have a relatively reduced ability to induce p21 and pRb expression levels. Ablation of p53 expression by the HPV 16 E6 gene induced E2F-1 expression, which plays a role in cellular survival, especially under hypoxia or gamma-irradiation. The steady-state level of p53 action produced by HPV 16 E7 did not induce apoptotic cell death or the production of the apoptotic regulators, the bcl-2 family and caspase-3, so it did not appear to participate in apoptotic signaling in response to hypoxia and ionizing radiation. Thus, the HPV 16 E7 oncoprotein did not increase the rate of cell death induced by p53, although p53 might play a role in apoptosis in HepG2 cells.

The Effects of Soybean Diet on the Diabetic Neuropathy in the Rats / 대한해부학회지

Neuropathy is a serious and disabling complication that contributes to increased morbidity and mortality in diabetic patients. There is progressive distal to proximal axonal atrophy that ultimately leads to Wallerian degeneration. This study was performed to identify the effect of soy bean on diabetic neuropathy using morphometry. Male Sprague-Dawley rats were grouped into control, diabetic with red chow diet and diabetic with soy bean diet. The myelinated nerve fibers were counted and fiber size distributions were evaluated in each group at 4 and 8 weeks, respectively. Diabetic neuropathy didn't develop in streptozotocin-induced diabetic rats at four weeks. At 8 weeks, the myelinated nerve fiber in diabetic with soy bean diet was larger in number than that in diabetic to which did not be administered insulin. The number of myelinated nerve fiber was not different between diabetic group with insulin and without insulin. Mean myelinated nerve fiber size was smaller in diabetic with soy bean diet than diabetic with red chow diet and control. Histogram of fiber size distribution was shifted to left in diabetic with red chow and soy bean diet groups compared to control. Light and electron microscopic findings showed marked degeneration of nerve fibers in diabetic with red chow diet but preservation in diabetic with soy bean diet. The level of glucose and HbA1c was lower in diabetic with soy bean diet than red chow diet. Soy bean could be effective in the protection of neuropathy induced by diabetes mellitus.

Expression of Cell Cycle Regulatory Proteins on the Solid Tumor Cell Line After Irradiation Under Hypoxia / 대한해부학회지

Human solid tumors are less well oxygenated than normal tissues. This leads to resistance to radiotherapy and anticancer chemotherapy. Many of genes encoding proteins induced by hypoxia are potential products for modifying the radiation response of normal or malignant tissues. Radiosensitivity or radioresisitance of the solid tumor cell lines can be exploited in overcoming the resistance to radiotherapy for cancer treatment. In this study, we investigated the radiosensitivity or radioresistance of the solid tumor cell line induced by hypoxia after radiation and the effect of hypoxia or/and irradiation on the expression of cell cycle regulatory proteins in the NIH3T3, MCF7 and HepG2 cell line. In normal cell line, NIH3T3, the cell death induced by irradiation was decreased by undergoing hypoxic treatment before radiation in the FACS and LDH assays. The percentage of cell death resulted in a significant increase by 70~80% in the NIH3T3 and HepG2 cell line after irradiation or hypoxia, but the cell death was significantly decreased after irradation under hypoxia in the HepG2 cells. However there is no difference in the cell death of MCF7 cells after same insults. DNA fragmentation was observed in only HepG2 cells under hypoxia by Heochst-PI nuclear staining, DNA gel electrophoresis and FACS analysis. In human breast cancer cell line MCF7, the level of E2F was more increased in hypoxia than normoxia, but was decreased after gamma-irradiation. However, it was shown that the effects of radiation can be changed by reoxygenation condition after hypoxia in human hepatoma cell line HepG2. The expression of E2F-1 was observed to decrease in HepG2 when cells were exposed to gamma-radiation after hypoxia. While investigating in MCF7 cells, the level of E2F-1 was increased under hypoxia. However, the expression of p53 decreased in hypoxia, though was increased after irradiation in the NIH3T3, MCF7 and HepG2 cell line. The increase of E2F-1 expression in MCF7 cells may be associated with hypoxic resistance in hypoxia-mediated apoptosis of tumors. The level of E2F may contribute to some critical factors of cellular repair function associated with DNA damage, and to deciding whether the cells will pass through cell cycle arrest or apoptosis.

The Effect of Ependymal Cell Transplantation on Nerve Regeneration after Spinal Cord Injury in Rats / 대한해부학회지

Nerve regeneration in the central nervous system has been studied by grafting various tissues and cells. Choroid plexus epithelial cells represent a continuation of ventricular ependymal cells and have the same origin as regarded as modified ependymal cells. To study the use of choroid plexus ependymal cell grafting for nerve regeneration in the spinal cord, the choroid plexus was excised from the lateral and fourth ventricles of adult Sprague-Dawley rats, minced into small fragments, and grafted at the T9 level in adult rat spinal cord transected or contused. In this study, transplants of choroid plexus ependymal cells were successfully used to promote functional and structural recovery after spinal cord transection and contusion. The area of damaged spinal cord was diminished after choroid plexus ependymal cells transplantation. Nearly normal anterior horn cells were observed immediately distal to the transected region. Tyrosine hydroxylase immunoreactive descending fibers were observed in the distal region beyond transected area. These findings indicate that choroid plexus ependymal cells have the ability to facilitate axonal growth, suggesting that they may be a promising candidate as graft for the promotion of nerve regeneration in the spinal cord.

Morphological Study of the Effects of Olfactory Bulb Transplants after Complete Spinal Cord Transection / 대한해부학회지

In the olfactory bulb, normal and transected olfactory axons are able to enter, regenerate, and reestablish lost synaptic contacts with their targets, throughout the lifetime of the organism. It was expected that studies of olfactory bulb ensheathing glia will provide important advances for the field of neural regeneration. Purpose of this study is to analyze morphologically the effects of olfactory bulb transplants into the cord after complete transection. Forty Sprague-Dawley rats were used in this study. Spinal cord of the rats were transected after laminectomy followed by insertion of chopped olfactory bulb tissues immediately and 3 weeks after the operation. In this study, transplants of olfactory bulb were successfully used to promote functional and structural recovery after complete spinal cord transection. The area of damaged spinal cord was greatly diminished after olfactory bulb transplantation. Nearly normal anterior horn cells were observed immediately distal to the transected region. Tyrosine hydroxylase immunoreactive descending fibers were observed in the distal region beyond transected area.

Quantitative Analysis of Agmatine by HPLC in Ischemic Brain / 대한해부학회지

Agmatine, a widely distributed molecule in mammalian tissues, shows neuroprotective effects in brain ischemia. We describe the neuroprotective effects of agmatine in the mouse MCAO model and the quantitative change of agmatine in ischemic injury. Brain ischemic injured mice were injected with agmatine (100 mg/kg of mouse, IP). Agmatine significantly reduced the infarct area after MCAO. Despite the similar patterns of agmatine change observed in control or agmatine injected animals, the agmatine levels of the penumbra were significantly higher than those of the striatum and the cerebral cortex during the early period (<1 hour after 2 hours of MCA occlusion). This suggests that the early period, during which agmatine levels increase in the brain, is the crucial period in terms of neuroprotective effect during ischemia.