WD12-1
Polygalae Radix extract increases an M2/M1 ratio of microglia and improves spinal cord injury
マイクログリアのM2/M1比を増加させる遠志による脊髄損傷の改善
Kominato Seiya（小湊 誠也），久保山 友晴，東田 千尋
Div. of Neuromedical Sci, Inst. of Natural Med, Univ. of Toyama
In the spinal cord injury, microglia and macrophages accumulate at the lesion site. Microglia and macrophages have two phenotypes. M1 induces inflammation and tissue damage. On the other hand, M2 shows anti-inflammatory effect and secrets axonal growth factor. In the injured spinal cord, M1 microglia and macrophages are increased and M2 microglia and macrophages are decreased. It may prevent axonal regeneration and locomotor recovery. In this study, we aimed to recover spinal cord injury by shifting phenotype of microglia and macrophages from M1 to M2 at the lesion site. Firstly, screening was performed by using 134 kinds of herbal drugs used in Japanese traditional medicine. Each water extract of the herbal drugs was treated to the cultured microglia for 24 h, M1 microglia and M2 microglia were determined by immunostaining, and ratios of M2 to M1 were calculated. As a result, only Polygalae Radix extract (10 μg/ml) increased twofold the ratio of M2 to M1 compared with control. When cultured microglia were pre-stimulated by IFN-γ (10 ng/ml) that decreased the ratio of M2 to M1, Polygalae Radix extract increased the ratio of M2 to M1. After Polygalae Radix extract (10 μg/ml) was treated to cultured microglia, conditioned medium was collected. When the conditioned medium was treated to cultured neurons, axonal outgrowth was promoted. In spinal cord injured mice, oral administration of Polygalae Radix extract (100 mg/kg/day for 28 days) improved locomotor dysfunction. These results suggest that Polygalae Radix extract increases the ratio of M2 to M1 and secretion of some axonal outgrowth factors from microglia. Those effects of Polygalae radix extract might to be related to functional recovery in spinal cord injury. | | WD12-2
Acteoside improves chronic spinal cord injury by activating skeletal muscle
アクテオサイドによる骨格筋活性化を介した慢性期脊髄損傷の改善
Kikuchi Takahiro（菊池 高弘）1，小谷 篤1，東田 千尋1
1Div. of Neuromedical Science, Inst. of Natural Medicine, Univ. of Toyama, Toyama, Japan
2Div. of Neuromedical Science, Inst. of Natural Medicine, Univ. of Toyama, Toyama, Japan
In acute and subacute phases of SCI, several options of treatments are experimentally effective. However, the recovery of motor function by those treatments are insufficient in case of chronic phase of SCI. Longitudinal study showed that skeletal muscle atrophy progressed post day of injury-dependently in human, and atrophy of skeletal muscle causes motor dysfunction in chronic SCI.The skeletal muscle secretes several factors named as myokine. Myokine may reach to and regulate the nervous system. However, direct evidences of SCI recovery mediated by myokines have not been shown. By our previous screening, we focused on acteoside as a stimulant of myokine secretion. In this study, we aimed to clarify the effects of acteoside on chronic SCI and its myokine-mediated mechanism.Primary cultured hindlimb skeletal muscle cells of newborn mice were treated by acteoside. Conditioned medium from acteoside-treated myocytes induced axonal growth. Acteoside also enhanced proliferation of primary cultured myocytes. Acteoside was administered (3 times/week) intramuscularly to SCI mice (T12 contusion injury) from 30 days after injury. During observation period (for 62 days after the injection start), locomotor function was significantly improved by acteoside. Wet weights of hindlimb skeletal muscle were significantly increased compared with vehicle-treated group. Released factors from myocytes by acteoside stimulation were investigated, and PKM2 was identified. Recombinant PKM2 enhanced axonal growth of cortical neurons in normal condition and CSPG-coated condition. In the present study, we discovered a drug activating skeletal muscle atrophy in chronic SCI, and new myokine PKM2 may play a role in the recovery phenomena. |
