Effects of Tetramethylpyrazine on Microglia Activation in Spinal Cord Compression Injury of Mice

Abstract

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.

Tetramethylpyrazine Mitigates Toxicity and Liver Oxidative Stress in Tibial Dyschondroplasia Chickens

“…On day 7 post hatch, after induction of TD, thiram group was equally divided into two groups designated as TD group (n=60) and TMP treatment group (n=60). TMP group was treated with Tetramethylpyrazine @ 30 mg/kg/day (Fan et al, 2011;Shin et al, 2013;Zhang et al, 2015) by intraperitoneal route from day 7 to day 18.…”

Mechanisms and Clinical Application of Tetramethylpyrazine (an Interesting Natural Compound Isolated from Ligusticum Wallichii): Current Status and Perspective

“…Recently, there is a piece of evidence for TMP on functional recovery and dendritic plasticity after ischemia [ 43 ]. The neuroprotective effects of TMP have also been tested on spinal cord injury [ 44 , 45 ]. Moreover, other researchers [ 46 ] explored anti-inflammatory properties of TMP in Alzheimer's disease.…”

Morphological and functional changes of microglia cultured under different oxygen concentrations and the analysis of related mechanisms

“…Microglia are mainly from bone marrow precursor and are innate immune cells of the central nervous system ( 7 ). Under normal conditions, the microglia are at resting state, controlling and maintaining the normal physiological environment of the central nervous system ( 8 , 9 ). When pathological changes such as stroke, trauma, infection, tumor and central nervous system degenerative diseases appear in the central nervous system, the microglia are activated and a large number of neurotoxic factors such as IL-1β and TNF-α are released, which triggers a series of inflammatory reactions and leads to the activation and migration of microglia around the area of the lesion ( 10 – 13 ).…”