Effects of tetramethylpyrazine on microglia activation in spinal cord compression injury of mice.
Secondary mechanisms, including inflammation and microglia activation, serve as targets for the development and application of pharmacological strategies in the management of spinal cord injury (SCI). Tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii (chuanxiong), has shown anti-inflammatory and neuroprotective effects against SCI. However, it remains uncertain whether the inflammation-suppressive effects of TMP play a modulatory role over microglia activation in SCI. The present study investigated the effects of TMP on microglia activation and pro-inflammatory cytokines in spinal cord compression injury in mice. For a real-time PCR measurement of pro-inflammatory cytokines, SCI was induced in mice by the clip compression method (30 g force, 1 min) and TMP (15 or 30 mg/kg, i.p.) was administered once, 30 minutes before the SCI induction. For immunohistochemistry, TMP (30 mg/kg, i.p.) treatment was given three times during the first 48 hours after the SCI. 30 mg/kg of TMP treatment reduced the up-regulation of TNF-α, IL-1β and COX-2 mRNA in the spinal tissue at four hours after the SCI induction. TMP also significantly attenuated microglia activation and neutrophil infiltration at 48 hours after the SCI induction. In addition, iNOS expression in the spinal tissue was attenuated with TMP treatment. These results suggest that TMP plays a modulatory role in microglia activation and may protect the spinal cord from or potentially delay secondary spinal cord injury.
Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, South Korea.
Jung-Won
JW
Shin
Ja-Young
JY
Moon
Ju-Won
JW
Seong
Sang-Hoon
SH
Song
Young-Jin
YJ
Cheong
Chulhun
C
Kang
Nak-Won
NW
Sohn
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D030004:Ligusticum; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000473:pathology*; D018696:Neuroprotective Agents; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013117:Spinal Cord Compression / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C101574:chuangxiong extract; C017953:tetramethylpyrazine