Abstract
BackgroundSpinal cord injury (SCI), including immediate mechanical injury and secondary injury, is associated with the inflammatory response, apoptosis and oxidative stress in response to traumatic injury. Tanshinone IIA (TIIA) is one of the major extracts obtained from Salvia miltiorrhiza BUNGE, which has anti-inflammatory and anti-apoptotic effects on many diseases. However, little is known about the effects of TIIA treatment on SCI. Therefore, the aim of the present study is to evaluate the pharmacological action of TIIA on secondary damage and the underlying mechanisms of experimental SCI in rats.Methodology/Principal FindingsSCI was generated using a weight drop device on the dorsal spinal cord via a two-level T9-T11 laminectomy. SCI in rats resulted in severe trauma, characterized by locomotor disturbance, edema, neutrophil infiltration, the production of astrocytes and inflammatory mediators, apoptosis and oxidative stress. TIIA treatment (20 mg/kg, i.p.) after SCI induced significant effects: (1) improved motor function (Basso, Beattie and Bresnahan scores), (2) reduced the degree of tissue injury (histological score), neutrophil infiltration (myeloperoxidase activity) and the expression of astrocytes, (3) inhibited the activation of SCI-related pathways, such as NF-κB and MAPK signaling pathways, (4) decreased the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and iNOS, (5) reduced apoptosis (TUNEL staining, and Bcl-2 and caspase-3 expression) and (6) reversed the redox state imbalance.Conclusions/SignificanceThe results clearly show that TIIA has a prominent protective effect against SCI through inhibiting the inflammatory response and apoptosis in the spinal cord tissue after SCI.
Highlights
Spinal cord injury (SCI) is a prevalent traumatic injury in the central nervous system (CNS) that leads to motor and sensory dysfunction in all ages
The results showed no significant difference in MPO activity between the sham and sham/Tanshinone IIA (TIIA) groups (Fig. 2F), but the MPO activity was increased in the SCI group
Effects of TIIA on NF-kB activation after SCI As the NF-kB pathway plays a key role in inflammation-related injury, we investigated the level of phosphorylated NF-kB (p-NFkB) and total NF-kB using western blot analysis to assess the therapeutic effect of TIIA at 24 h after SCI (Fig. 4A and 4B)
Summary
Spinal cord injury (SCI) is a prevalent traumatic injury in the central nervous system (CNS) that leads to motor and sensory dysfunction in all ages. The secondary damage to the spinal cord develops within from minutes to hours following initial mechanical damage, and leads to a cascade of extracellular and intercellular events, including the infiltration of inflammatory cells, the destruction of neuronal and glial cells, neuronal dysfunction and death, and oxidative stress. The pathophysiological mechanisms of SCI are complicated During this period, inflammatory reactions are a crucial process of the secondary injury [3,4]. Previous studies have shown that apoptosis, which is regulated primarily through the caspase and Bcl-2 families [9,10], is an important event in the secondary injury after SCI [11]. Spinal cord injury (SCI), including immediate mechanical injury and secondary injury, is associated with the inflammatory response, apoptosis and oxidative stress in response to traumatic injury. The aim of the present study is to evaluate the pharmacological action of TIIA on secondary damage and the underlying mechanisms of experimental SCI in rats
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