• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.5
• /
• pp.461-465
• /
• 2015

Microglia, the resident macrophages in the central nervous system, can rapidly respond to pathological insults. Toll-like receptor 2 (TLR2) is a pattern recognition receptor that plays a fundamental role in pathogen recognition and activation of innate immunity. Although many previous studies have suggested that TLR2 contributes to microglial activation and subsequent pathogenesis following brain tissue injury, it is still unclear whether TLR2 has a role in microglia dynamics in the resting state or in immediate-early reaction to the injury in vivo. By using in vivo two-photon microscopy imaging and $Cx3cr1^{GFP/+}$ mouse line, we first monitored the motility of microglial processes (i.e. the rate of extension and retraction) in the somatosensory cortex of living TLR2-KO and WT mice; Microglial processes in TLR2-KO mice show the similar motility to that of WT mice. We further found that microglia rapidly extend their processes to the site of local tissue injury induced by a two-photon laser ablation and that such microglial response to the brain injury was similar between WT and TLR2-KO mice. These results indicate that there are no differences in the behavior of microglial processes between TLR2-KO mice and WT mice when microglia is in the resting state or encounters local injury. Thus, TLR2 might not be essential for immediate-early microglial response to brain tissue injury in vivo.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.4
• /
• pp.207-211
• /
• 2004

The purpose of the present study was to evaluate the expression of cardiac marker protein in rabbit cardiac tissue that was exposed to ischemic preconditioning (IPC), or ischemiareperfusion injury (IR) using two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). We compared 2DE gels of control (uninjured) cardiac tissue with those of IPC and IR cardiac tissue. Expression of one protein was detected in IR heart tissue, however the protein was not detected in the samples of control and IPC tissue. To further characterize the detected protein molecule, the protein in the 2D gel was isolated and subjected to trypsin digestion, followed by MALDI-MS. The protein was identified as myoglobin, which was confirmed also by Western blot analysis. These results are consistent with previous studies of cardiac markers in ischemic hearts, indicating myoglobin as a suitable marker of myocardial injury. In addition, the present use of multiple techniques indicates that proteomic analysis is an appropriate means to identify cardiac markers in studies of IPC and IR.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.1
• /
• pp.93-100
• /
• 1999

The present study was designed to assess the roles of $PLA_2$ activation and arachidonic acid (AA) metabolites in hypoxia-induced renal cell injury. Hypoxia increased LDH release in a dose-dependent manner in rabbit renal cortical slices, and this increase was significant after 20-min hypoxia. The hypoxia-induced LDH release was prevented by amino acids, glycine and alanine, and extracellular acidosis (pH 6.0). Buffering intracellular $Ca^{2+}$ by a chelator, but not omission of $Ca^{2+}$ in the medium produced a significant reduction in hypoxia-induced LDH release. The effect of hypoxia was blocked by $PLA_2$ inhibitors, mepacrine, butacaine, and dibucaine. A similar effect was observed by a 85-kD $cPLA_2$ inhibitor $AACOCF_3.$ AA increased hypoxia-induced LDH release, and albumin, a fatty acid absorbent, prevented the LDH release, suggesting that free fatty acids are involved in hypoxia-induced cell injury. These results suggest that $PLA_2$ activation and its metabolic products play important roles in pathogenesis of hypoxia-induced cell injury in rabbit renal cortical slices.

• International Journal of Oral Biology
• /
• v.45 no.3
• /
• pp.84-91
• /
• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

• Advances in Traditional Medicine
• /
• v.7 no.5
• /
• pp.556-563
• /
• 2008

Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. The expression of c-Fos is sometimes used as a marker of increased neuronal activity. We have prepared the aqueous extract of amygdalin from Armeniacae semen for pain control. In the present study, we investigated the effects of amygdalin on the recovery rate of the locomotor function and on the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region following sciatic crushed nerve injury in rats. Walking track analysis for the evaluation of functional recovery and immunohistochemistry for the c-Fos expression were used in this study. In the present results, characteristic gait change with dropping of the sciatic function index (SFI) was observed and c-Fos expression in the vlPAG was suppressed following sciatic crushed nerve injury in rats. Amygdalin enhanced SFI value and restored c-Fos expression in the vlPAG to the control value. The present our study indicated that amygdalin activates neurons in the vlPAG, and it facilitates functional recovery following peripheral nerve injury.

• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.3
• /
• pp.143-147
• /
• 2005

Following peripheral nerve injury, excessive nociceptive inputs result in diverse physiological alterations in the spinal cord substantia gelatinosa (SG), lamina II of the dorsal horn. Here, I report the alterations of excitatory or inhibitory transmission in the SG of a rat model for neuropathic pain ('spared nerve injury'). Results from whole-cell recordings of SG neurons show that the number of distinct primary afferent fibers, identified by graded intensity of stimulation, is increased at 2 weeks after spared nerve injury. In addition, short-term depression, recognized by paired-pulse ratio of excitatory postsynaptic currents, is significantly increased, indicating the increase of glutamate release probability at primary afferent terminals. The peripheral nerve injury also increases the amplitude, but not the frequency, of spontaneous inhibitory postsynaptic currents. These data support the hypothesis that peripheral nerve injury modifies spinal pain conduction and modulation systems to develop neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
• /
• v.16 no.6
• /
• pp.387-392
• /
• 2012

In this study, we examined the antinociceptive effect of Cyperi rhizoma (CR) and Corydalis tuber (CT) extracts using a chronic constriction injury-induced neuropathic pain rat model. After the ligation of sciatic nerve, neuropathic pain behavior such as mechanical allodynia and thermal hyperalgesia were rapidly induced and maintained for 1 month. Repeated treatment of CR or CT (per oral, 10 or 30 mg/kg, twice a day) was performed either in induction (day 0~5) or maintenance (day 14~19) period of neuropathic pain state. Treatment of CR or CT at doses of 30 mg/kg in the induction and maintenance periods significantly decreased the nerve injury-induced mechanical allodynia. In addition, CR and CT at doses of 10 or 30 mg/kg alleviated thermal heat hyperalgesia when they were treated in the maintenance period. Finally, CR or CT (30 mg/kg) treated during the induction period remarkably reduced the nerve injury-induced phosphorylation of NMDA receptor NR1 subunit (pNR1) in the spinal dorsal horn. Results of this study suggest that extracts from CR and CT may be useful to alleviate neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.3
• /
• pp.251-262
• /
• 1997

Peripheral nerve injury sometimes leads to neuropathic pain and depletion of calcitonin gene related-peptide (CGRP) and substance P (SP) in the spinal cord. However, the pathophysiological mechanisms for depletion of CGRP and SP following the neurorathic injury are still unknown. This study was performed to see whether the distribution of immunoreactivity for CGRP and SP in the superficial dorsal horn and dorsal root ganglia(DRG) was related to the distance between the DRG and injury site. To this aim, we compared two groups of rats; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerve (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunostaining with SP and CGRP antibody was done in the S1-S3 spinal cord and DRG of the two groups 1 and 12 weeks after the injury. The results obtained are as follows: 1. The immunoreactivity for CGRP and SP in the ipsilateral superficial dorsal horn and DRG decreased 1 and 12 weeks after neuropathic nerve injury. 2. The immunoreactive area of SP and CGRP in the S1 dorsal horn was smaller in the S123 group than in the S34 group, whereas that in the S3 dorsal horn was not significantly different between the two groups. The number of SP-immunoreactive DRG cells decreased on the neuropathic side as compared to the sham group's in all DRGs of experimental groups except the S1 DRG of the S34 group. These results suggest that the amounts of SP and CGRP in the dorsal horn and DRG following neuropathic injury inversely decrease according to the distance between the DRG and injury site.

• Proceedings of the PSK Conference
• /
• 2000.10a
• /
• pp.173.1-173.1
• /
• 2000

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.3
• /
• pp.161-168
• /
• 2009

In the peripheral nerves, injury-induced cytokines and growth factors perform critical functions in the activation of both the MEK/ERK and JAK/STAT3 pathways. In this study, we determined that nerve injury-induced ERK activation was temporally correlated with STAT3 phosphorylation at the serine 727 residue. In cultured Schwann cells, we noted that ERK activation is required for the serine phosphorylation of STAT3 by neuropoietic cytokine interleukin-6 (IL-6). Serine phosphorylated STAT3 by IL-6 was transported into Schwann cell nuclei, thereby indicating that ERK may regulate the transcriptional activity of STAT3 via the induction of serine phosphorylation of STAT3. Neuregulin-1 (NRG) also induced the serine phosphorylation of STAT3 in an ERK-dependent fashion. In contrast with the IL-6 response, serine phosphorylated STAT3 induced by NRG was not detected in the nucleus, thus indicating the non-nuclear function of serine phosphorylated STAT3 in response to NRG. Finally, we determined that the inhibition of ERK prevented injury-induced serine phosphorylation of STAT3 in an ex-vivo explants culture of the sciatic nerves. Collectively, the results of this study show that ERK may be an upstream kinase for the serine phosphorylation of STAT3 induced by multiple stimuli in Schwann cells after peripheral nerve injury.