Dl‐3‐n‐butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF‐κB signalling

Abstract

In this study, we examined the neuroprotective effects and anti‐inflammatory properties of Dl‐3‐n‐butylphthalide (NBP) in Sprague‐Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL‐positive cells at 7 days post‐injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF‐κB expression at 1 day post‐injury. In a co‐culture system with BV‐2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV‐2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV‐2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF‐κB expression in BV‐2 cells. Our findings demonstrate that NBP may have neuroprotective and anti‐inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF‐κB signalling.

The microglial activation profile and associated factors after experimental spinal cord injury in rats

“…Similar findings demonstrated that microglia activation had resulted in inflammatory response in rats following SCI, and Dl-3-n-butylphthalide may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-kappaB signaling. 20 Next, astrocytes were activated to further enhance the inflammation response. 32 , 33 The finding showed after SCI, reactive astrocytes had undergone M1 microglia-induced necroptosis, partially through TLR/MyD88 signaling, and suggested that inhibiting astrocytic necroptosis may be beneficial for preventing secondary SCI.…”

“…All surgeries were performed by the same surgeon following the methods outlined previously. 14 , 20 Briefly under aseptic conditions, the T10 spinal cord segment was fully exposed by T9-T11 dorsal laminectomies leaving the dura intact using an operating microscope (M500-N, Leica, Heerbrugg, Switzerland). Subsequently, compressive injury was induced by a 2-minute compression SCI using a 10 g aneurysm clip (5.0 mm*0.8 mm, Kent Scientific, Torrington, CT, USA; Figure 1 ).…”

Bone marrow stromal cells improved functional recovery in spinal cord injury rats partly via the Toll‑like receptor‑4/nuclear factor‑κB signaling pathway

“…The inflammatory response in the injured spinal cord is a key mechanism mediating the secondary injury stage after SCI (2,25). The cells at the site of injury trigger the inflammatory response through the activation of multiple receptors, including TLR4, in immune-competent cells, neurons and astrocytes (26). These receptors promote the activation of NF-κB, a multifunctional transcription factor that controls several pro-inflammatory and stress responses, which may ultimately induce apoptosis, neuronal degeneration and disease progression (27).…”

Dl‑3n‑butylphthalide improves spatial learning and memory in rats with vascular dementia by reducing autophagy via regulation of the mTOR signaling pathway

“…Based on its multi-target therapeutic properties, NBP has demonstrated an important role in a number of nervous system diseases, including amyotrophic lateral sclerosis (10), Parkinson's disease (11) and VD (12), as well as models of Alzheimer's disease (13). Studies have also demonstrated that multiple mechanisms are involved in the neuroprotective effects of NBP, including anti-inflammatory effects, suppression of oxidative stress, inhibition of platelet aggregation and anti-apoptosis (14)(15)(16)(17). However, little is known about the protective role of NBP against chronic ischemia-induced excessive autophagy in VD.…”