Effect of Acupuncture on the Tlr2/4-Nf-κB Signalling Pathway in a Rat Model of Traumatic Brain Injury

Abstract

ObjectiveTo study the effect of acupuncture on the TLR2/4-NF-κB signalling pathway in the cortex of Sprague-Dawley rats following traumatic brain injury (TBI), and investigate the possible mechanism underlying the effects of acupuncture on scar repair.MethodsTBI was established using Feeney’s free-falling epidural percussion model. In total, 108 rats were randomly divided into a normal group (n=18), untreated TBI model group (TBI group, n=36) and manual acupuncture-treated TBI group (TBI+MA, n=36). Each group of rats was subdivided into three time groups: 3-day (3d), 7-day (7d) and 14-day (14d). No treatment was given to rats in the normal and TBI groups. The TBI+MA group received manual acupuncture at GV20, GV26, GV16 through GV15, and bilateral LI4. mRNA expression of TLR2, TLR4, NF-κB and protein in the rat cortices was quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blot analyses.ResultsThe modified neurological severity score (mNSS) scores of the TBI+MA group were improved compared with baseline scores 12 hours after modelling, and improved at 7d and 14d compared with the TBI group (P<0.05), while the score of the TBI group did not improve until 14d compared to baseline. mRNA and protein expression of TLR2, TLR4 and NF-κB in the TBI group were higher than the normal group at 3d (P<0.05), reached a peak at 7d, then began to decrease at 14d. mRNA and protein expression of TLR2, TLR4 and NF-κB were higher in the TBI+MA group compared with the TBI group at 3d (P<0.05), were significantly down-regulated at 7d (P<0.01), and decreased to normal levels at 14d.ConclusionsAcupuncture has a bidirectional regulatory effect on the TLR2/4-NF-κB signalling pathway-related genes TLR2, TLR4 and NF-κB in the TBI rat cortex, promoting their expression in the early stage and inhibiting it in the later stage.

Activation of GABAB Receptor Suppresses Diabetic Neuropathic Pain through Toll-Like Receptor 4 Signaling Pathway in the Spinal Dorsal Horn

“…The Toll-like family, including TLR2 and TLR4, is correlated to innate immune responses and is also related to adaptive immunity [27, 28]. TLR2/4, especially TLR4, links microglial activation and nerve injury, which play an important role in the occurrence of neuropathic pain [12, 29].…”

“…TLRs are extensively distributed in the central and peripheral nervous systems, including in glial cells and neurons. As an important member of the TLR family, TLR4 is mainly located in primary sensory neurons, microglia, and astrocytes [29]. Previous studies have reported that TLR4 is upregulated in the spinal cord and dorsal root ganglion in paclitaxel-induced neuropathic pain, which is considered to have analogous mechanisms with DNP [30].…”

Manual acupuncture relieves microglia-mediated neuroinflammation in a rat model of traumatic brain injury by inhibiting the RhoA/ROCK2 pathway

“…For the TBI group and the TBI + MA group, Feeney’s freefall epidural impact method was used to construct a rat model of moderate craniocerebral injury. 12 The rats were weighed and anesthetized via an intraperitoneal injection of 30 mg/mL pentobarbital sodium (45 mg/kg). After anesthesia, the scalp was cut 2 mm to the right of the skull median line and separated from the skull.…”

“…MA inhibits the excessive formation of glial scars after TBI in rats, thus inhibiting neuroinflammation. 12 Microglia are a component of glial scars. Moreover, neuroinflammation after TBI is accompanied by the activation and polarization of microglia.…”

Changes in cerebral glucose metabolism after acupuncture at KI3 in spontaneously hypertensive rats: a positron emission tomography study

“…Furthermore, NF-κB inhibition within the bilateral PVN attenuates an Ang II-induced hypertensive response by reducing proinflammatory cytokines. 24 Studies have shown that acupuncture can inhibit NF-κB signaling pathways in multiple brain regions, 28,29 and therefore we speculate that the central antihypertensive mechanism of acupuncture at KI3 may be related to the following two points: (1) acupuncture inhibits the RAS and lowers BP by inhibiting components such as angiotensinogen produced by astrocytes in the thalamus and hypothalamus; and (2) acupuncture reduces the discharge of sympathetic neurons by inhibiting NF-κB and reducing proinflammatory cytokines in the hypothalamus, thereby attenuating an Ang II-induced hypertensive response.…”