Wei Jin

Nanjing University of Traditional Chinese Medicine, Nan-ching, Jiangsu Sheng, China

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Publications (26)75.97 Total impact

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    ABSTRACT: Erythropoietin has demonstrated neuroprotective effects against traumatic spinal cord injury (SCI), but the underlying mechanisms remain unclear. The signaling pathway of an antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), has been shown to play an important role in protecting SCI-induced secondary spinal cord damage. This study was undertaken to explore the effect of recombinant human erythropoietin (rhEPO) on the activation of Nrf2 signaling pathway and secondary spinal cord damage in rats after SCI. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. Three groups were analyzed: (1) sham group, (2) SCI group, and (3) SCI + rhEPO group (n = 16 per group). In the SCI + rhEPO group, rhEPO was administered at a dose of 5,000 IU/kg at 30 minutes after SCI. Spinal cord samples were extracted at 72 hours after the trauma. As a result, we found that the treatment with rhEPO markedly up-regulated the messenger RNA expressions and activities of Nrf2 signaling pathway-related agents, including Nrf2, NAD(P)H:quinone oxidoreductase 1(NQO1), and glutathione S-transferase. The administration of rhEPO also significantly ameliorated the secondary spinal cord damage, as shown by a decreased severity of locomotion deficit, spinal cord edema, and apoptosis. Post-SCI rhEPO administration induces Nrf2-mediated cytoprotective response in the injured spinal cord, and this may be a mechanism whereby rhEPO improves the outcome following SCI.
    The journal of trauma and acute care surgery. 05/2014; 76(5):1228-34.
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    ABSTRACT: Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether curcumin, a novel Nrf2 activator, can protect the spinal cord against SCI-induced inflammatory damage. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. The spinal cords spanning the injury site about 0.8 cm were collected for testing. There were three groups: (a) sham group; (b) SCI group; and (c) SCI + curcumin group. We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by electrophoretic mobility shift assay, concentrations of tumor necrosis factor-α, interleukin-1β and interleukin-6 by enzyme-linked immunosorbent assay, hindlimb locomotion function by Basso, Beattie, and Bresnahan rating, spinal cord edema by the wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis. Induction of the Nrf2 activity by curcumin markedly decreased NF-κB activation and inflammatory cytokines production in the injured spinal cord. Administration of curcumin also significantly ameliorated the secondary spinal cord damage, as shown by decreased severity of locomotion deficit, spinal cord edema, and apoptosis. Post-SCI curcumin administration attenuates the inflammatory response in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome following SCI.
    Agents and Actions 01/2014; · 1.59 Impact Factor
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    ABSTRACT: Background Curcumin, a polyphenolic compound extracted from the plant turmeric, has protective effects on spinal cord injury (SCI) through attenuation of inflammatory response. This study was designed to detect whether curcumin modulates toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) inflammatory signaling pathway in the injured rat spinal cord following SCI. Methods Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. There were three groups: (a) sham group; (b) SCI group; and (g) SCI + curcumin group. We measured TLR4 gene and protein expression by real-time polymerase chain reaction and western blot analysis; NF-κB activity by electrophoretic mobility shift assay, inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels by enzyme-linked immunosorbent assay, hindlimb locomotion function by Basso, Beattie, and Bresnahan rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. Results The results showed that SCI induced the up-regulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat spinal cord. Treatment with curcumin following SCI markedly down-regulated the levels of these agents related to the TLR4/NF-κB inflammatory signaling pathway. Administration of curcumin also significantly ameliorated SCI induced hind limb locomotion deficits, spinal cord edema, and apoptosis. Conclusions Post-SCI curcumin administration attenuates the TLR4/NF-κB inflammatory signaling pathway in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome following SCI.
    The journal of spinal cord medicine 01/2014; · 1.54 Impact Factor
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    ABSTRACT: Aim The present study aimed to investigate the effects of curcumin on the levels of spinal cord labile zinc (Zn) and inflammatory cytokines in rats after traumatic spinal cord injury (SCI). Methods Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. There were three groups: (a) sham group; (b) SCI group; and (c) SCI+curcumin group. We measured spinal labile zinc by N-(6-Methoxy-8-quinolinyl)-4-methylbenzenesulfonamide (TSQ) fluorescence staining, inflammatory cytokines such as, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay (ELISA), hindlimb locomotion function by Basso, Beattie, and Bresnahan (BBB) rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. Results The results showed that SCI caused a significant increase of labile zincand inflammatory cytokines in the injured rat spinal cord. Treatment with curcumin following SCI markedly down-regulated the levels of these agents and ameliorated SCI-induced hindlimb locomotion deficits, spinal cord edema, and apoptosis. Conclusions Curcumin treatment attenuates the increase of labile zinc and the expression of inflammatory cytokines in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome following SCI.
    Journal of Surgical Research 01/2014; · 2.02 Impact Factor
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    ABSTRACT: Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect the spinal cord against SCI-induced inflammatory damage. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. Three groups were analyzed: a sham group, a SCI group, and a SCI+rhEPO group (n=16 per group). We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by an electrophoretic mobility shift assay (EMSA). We also measured the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay (ELISA); we also measured hindlimb locomotion function by the Basso, Beattie, and Bresnahan (BBB) rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. The results showed that the induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokines production in the injured spinal cord. Administration of tBHQ also significantly attenuated SCI induced hindlimb locomotion deficits, spinal cord edema, and apoptosis. To conclude, pre-treatment with tBHQ could attenuate the spinal cord inflammatory response after SCI.
    Annals of clinical and laboratory science 01/2014; 44(2):151-7. · 0.88 Impact Factor
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    ABSTRACT: Nerve conduit provides a promising strategy for nerve regeneration, and the proper microenvironment in the lumen could improve the regeneration. Our previous work had demonstrated that linear ordered collagen scaffold (LOCS) could effectively guide the oriented growth of axons. Laminin is known as an important nerve growth promoting factor and can facilitate the growth cone formation. In addition, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) can effectively improve the nerve regeneration after nerve injuries. However, in practice, diffusion caused by the body fluids is the major obstacle in their applications. To retain CNTF or BDNF on the scaffolds, we produced collagen binding CNTF (CBD-CNTF), collagen binding BDNF (CBD-BDNF) and laminin binding CNTF (LBD-CNTF), laminin binding BDNF (LBD-BDNF) respectively. In this work, we developed laminin modified LOCS fibers (L × LOCS) by chemical cross-linking LOCS fibers with laminin. Collagen binding or laminin binding neurotrophic factors were combined with LOCS or L × LOCS, and then filled them into the collagen nerve conduit. They were found to guide the ordered growth of axons, and improve the nerve functional recovery in the rat facial nerve transection model. The combination of CNTF and BDNF greatly enhanced the facial nerve regeneration and functional recovery.
    Biomaterials 10/2012; · 8.31 Impact Factor
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    ABSTRACT: Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play a crucial role in protection against TBI induced inflammatory response in the brain. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect mice brain against TBI-induced inflammatory damage. Adult male ICR mice were randomly divided into three groups: (1) sham+vehicle group; (2) TBI+vehicle group; and (3) TBI+tBHQ group (n=12 per group). Closed head injury was adopted using Hall's weight-dropping method. We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by electrophoretic mobility shift assay (EMSA), concentrations of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), brain oedema by wet/dry weight method, and cortical apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis. Induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokine production in the injured brain. Administration of tBHQ also significantly attenuated TBI-induced brain oedema and cortical apoptosis. Pre-treatment with tBHQ could attenuate the cerebral inflammatory response after TBI.
    Injury 04/2011; 42(7):714-8. · 1.93 Impact Factor
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    ABSTRACT: In our previous studies, antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has been shown to play an important role in protecting traumatic brain injury (TBI)-induced acute lung injury (ALI). This study was designed to explore whether recombinant human erythropoietin (rhEPO) administration modulates pulmonary Nrf2 signaling pathway in a murine TBI model. Closed head injury was made by Hall's weight-dropping method. The rhEPO was administered at a dose of 5,000 IU/kg 30 minutes after TBI. Pulmonary capillary permeability, wet or dry weight ratio, apoptosis, Nrf2 and its downstream cytoprotective enzymes including NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase were investigated at 24 hours after TBI. We found that treatment with rhEPO markedly ameliorated TBI-induced ALI, as characterized by decreased pulmonary capillary permeability, wet or dry weight ratio, and alveolar cells apoptosis. Administration of rhEPO also significantly upregulated the mRNA expressions and activities of Nrf2 signaling pathway-related agents, including Nrf2, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase. The results of this study suggest that post-TBI rhEPO administration may induce Nrf2-mediated cytoprotective response in the lung, and this may be a mechanism whereby rhEPO reduces TBI-induced ALI.
    The Journal of trauma 03/2011; 71(3):680-6. · 2.35 Impact Factor
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    ABSTRACT: Brain derived neurotrophic factor (BDNF) has been shown to ameliorate recovery after intracerebral hemorrhage (ICH). The injured brain tissue after ICH is surrounded by hematoma formed from hemorrhage. Fibrin is abundant in hematoma, which could be a binding target for BDNF. In this work, we have fused a fibrin-binding domain (FBD) to BDNF (FBD-BDNF), and results demonstrate that FBD-BDNF has specific binding ability to fibrin and is retained in hematoma. Using the rat ICH model induced by bacterial collagenase, injected FBD-BDNF has been concentrated and retained at the hematoma. FBD has facilitated BDNF to exert targeting neuroprotective effect to the injured brain tissue around the hematoma after ICH. FBD-BDNF has significantly reduced the hemotoma volume, reduced tissue loss, promoted neural regeneration, and improved the rat behavioral performance.
    Biomaterials 02/2011; 32(12):3244-52. · 8.31 Impact Factor
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    ABSTRACT: Erythropoietin (EPO) has demonstrated neuroprotective effects against traumatic brain injury (TBI), but the underlying mechanisms remain unclear. The signaling pathway of an antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), has been shown in our previous studies to play an important role in protecting mice from TBI-induced secondary brain injury. The present study explored the effect of recombinant human erythropoietin (rhEPO) on cerebral activation of the Nrf2 signaling pathway and secondary brain injury in mice after TBI. Adult male ICR mice were randomly divided into three groups: (1) Sham group; (2) TBI group; and (3) TBI+rhEPO group (n = 12 per group). Closed head injury was performed using Hall's weight-dropping method. rhEPO was administered at a dose of 5,000 IU/kg at 30 min after TBI. Brain samples were extracted at 24 hr after the trauma. The treatment with rhEPO markedly up-regulated the mRNA expression and activities of Nrf2 and its downstream cytoprotective enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1). Administration of rhEPO also significantly ameliorated the secondary brain injury, as shown by decreased severity of neurological deficit, brain edema, and cortical apoptosis. In summary, post-TBI rhEPO administration induces Nrf2-mediated cytoprotective responses in the injured brain, and this may be a mechanism whereby rhEPO improves the outcome following TBI.
    Annals of clinical and laboratory science 01/2011; 41(1):25-32. · 0.88 Impact Factor
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    ABSTRACT: In the treatment of spinal cord injury, implantation of scaffolding biomaterials and the addition of neuroprotective factors will promote neural regeneration. It has been demonstrated in our previous work that linear ordered collagen scaffold (LOCS) will bridge neural regeneration after the injury of spinal cord hemisection, and BDNF fused with a collagen binding domain (CBD-BDNF) can bind to collagen specifically to exert the neuroprotective effect. Besides neuroprotective factors, the lack of axon regeneration of the injured spinal cord has been attributed partially to regeneration inhibitors such as myelin associated proteins and chondroitin sulfate proteoglycans (CSPGs). Epidermal growth factor receptor (EGFR) activation is downstream of the signaling pathways of these inhibitors. Here, the monoclonal antibody, 151IgG that inhibits signaling of EGFR was used to neutralize EGFR. 151IgG was cross-linked to LOCS and CBD-BDNF bound to LOCS to make a triple-functional biomaterial for neural regeneration (bridging, prompting growth and neutralizing growth inhibitors). This triple-functional device was tested in a 6 mm transected SCI model. Results showed that this collagen scaffold with the addition of 151IgG and CBD-BDNF provided effective bridging and stimulation effects for neural regeneration, recovery of electrical transmission of synapses and preventing the formation of glial scars in the extreme transected rat SCI model.
    Biomaterials 12/2010; 31(35):9212-20. · 8.31 Impact Factor
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    ABSTRACT: Spinal cord crushed injury is clinically common. Promoting targeted neural regeneration at the crushed site of spinal cord could be important for the repair. It has been demonstrated in our previous work that native human BDNF fused with a collagen-binding domain (CBD-BDNF) can bind to collagen specifically to exert the neurotrophic effect on promoting axonal regeneration. After injury, collagen is highly accumulated at the injury site. We thus speculate that CBD-BDNF will bind to the extracellular matrix collagen and concentrate at the injury site to improve the therapy. Using the rat spinal cord crushed injury model, we have found that CBD-BDNF by one-time intrathecally injection could be retained and concentrated at the injury site for a longer time than native BDNF without collagen-binding domain. CBD-BDNF could promote better neural regeneration and locomotion recovery.
    Biomaterials 11/2010; 31(33):8634-41. · 8.31 Impact Factor
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    ABSTRACT: Traumatic brain injury (TBI) can induce intestinal inflammatory response and mucosal injury. Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to prevent oxidative stress and inflammatory response in gut after TBI. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), an Nrf2 inducer, can protect against TBI-induced intestinal inflammatory response and mucosal injury in mice. Adult male ICR mice were randomly divided into three groups: (1) sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + tBHQ group (n = 12 per group). Closed head injury was adopted using Hall's weight-dropping method. Intestinal mucosa apoptosis and inflammatory-related factors, such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), were investigated at 24 h after TBI. As a result, we found that oral treatment with 1% tBHQ prior to TBI for one week markedly decreased NF-κB activation, inflammatory cytokines production, and ICAM-1 expression in the gut. Administration of tBHQ also significantly attenuated TBI-induced intestinal mucosal apoptosis. The results of the present study suggest that tBHQ administration could suppress the intestinal inflammation and reduce the mucosal damage following TBI.
    Mediators of Inflammation 01/2010; 2010:502564. · 3.88 Impact Factor
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    ABSTRACT: Erythropoietin (Epo) has been gaining great interest for its potential neuroprotective effect in various neurological insults. However, the molecular mechanism underlying how Epo exerts the function is not clear. Recent studies have indicated that Zn(2+) may have a key role in selective cell death in excitotoxicity after injury. In the present study, we studied the effect of recombinant human Epo (rhEpo) in zinc-induced neurotoxicity both in vitro and in vivo. Exposure of cultured hippocampal neurons to 200 muM ZnC1(2) for 20 min resulted in remarkable neuronal injury, revealed by assessing neuronal morphology. By measuring mitochondrial function using MTT assay, we found that application of rhEpo (0.1 U/ml) 24 h before zinc exposure resulted in a significant increase of neuronal survival (0.6007+/-0.2280 Epo group vs 0.2333+/-0.1249 in control group; n=4, p<0.01). Furthermore, we demonstrated that administration of rhEpo (5,000 IU/kg, intraperitoneal) 30 min after traumatic brain injury (TBI) in rats dramatically protected neuronal death indicated by ZP4 staining, a new zinc-specific fluorescent sensor which has been widely used to indicate neuronal damage after excitotoxic injury (n=5/group, p<0.05). Neuronal damage was also assessed by Fluoro-Jade B (FJB) staining, a highly specific fluorescent marker for the degenerating neurons. Consistent with ZP4 staining, we found the beneficial effects of rhEpo on neuronal survival in hippocampus after TBI (n=5/group, p<0.05). Our results suggest that rhEpo can significantly reduce the pathological Zn(2+) accumulation in rat hippocampus after TBI as well as zinc-induced cell death in cultured cells, which may potentially contribute to its neuronal protection after excitotoxic brain damage.
    Brain research 08/2009; 1289:96-105. · 2.46 Impact Factor
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    ABSTRACT: Secondary brain damage plays a critical role in the outcome of patients with traumatic brain injury (TBI). The mechanisms underlying secondary brain damage are complex. A target that can interrupt multiple mechanisms underlying secondary brain damage may represent a promising new therapeutic approach for TBI. NF-E2-related factor 2 (Nrf2) is the key regulator in reducing oxidative stress, inflammatory damage, and the accumulation of toxic metabolites, which are all involved in secondary brain damage after TBI. Therefore, Nrf2 might represent a new direction for the treatment of TBI. However, the expression pattern of Nrf2 after TBI has not yet been studied. This study involved the detection of Nrf2 mRNA levels by reverse-transcriptase polymerase chain reaction, and its nuclear protein levels by Western blot from 3 hour to 72 hour after TBI. Nrf2 distribution in the brain after TBI was also investigated by immunohistochemistry. After TBI, the nuclear Nrf2 protein level is significantly increased, whereas its mRNA level remains unchanged. Increased Nrf2 immunostaining was detected not only in the vulnerable regions but also in the brain barrier system. Nrf2 might play a protective role in the brain after TBI, possibly by reducing oxidative stress and brain edema.
    The Journal of trauma 06/2009; 66(5):1431-5. · 2.35 Impact Factor
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    ABSTRACT: The objective of this study was to determine the effect of erythropoietin (Epo) on the intestinal labile zinc and the inflammatory factor in rats after traumatic brain injury (TBI). Male Sprague-Dawley rats were randomly divided into nine groups: (a) normal group; (b) sham-operation group; (c, d, e, f, and g) TBI group, killed at 1 hour, 6 hour, 24 hour, and 72 hour and 7 days postinjury, respectively; (h and i) TBI + saline and TBI + Epo, killed at 24 hour or 72 hour postinjury. Parietal brain contusion was produced by a free-falling weight on the exposed dura of the right parietal lobe. Intestinal labile zinc, the tumor necrosis factor-alpha, interleukin (IL)-8, and wet/dry weight ratio were investigated in different groups. The gut contains a certain amount of labile zinc in normal animals and TBI caused obviously gradual increment of intestinal liabled zinc. The levels of inflammatory mediators and the gut wet/dry weight ratio were also found to increase in the trauma group (p < 0.05). There was a highly positive correlation between the abundance of zinc fluorescence and these proinflammation factors. Epo significantly reduced the intestinal labile zinc, the inflammatory mediators, and the gut wet/dry weight ratio compared with TBI group (p < 0.05). Epo can protect intestine from TBI-induced injury by attenuating intestinal inflammation and labile zinc accumulation in vivo.
    The Journal of trauma 03/2009; 66(3):730-6. · 2.35 Impact Factor
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    ABSTRACT: Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in the regulation of traumatic brain injury (TBI)-induced acute lung injury (ALI). Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Pulmonary capillary permeability (PCP), wet/dry weight ratio, apoptosis, inflammatory cytokines and antioxidant/detoxifying enzymes were measured at 24 h after TBI. Mice lacking Nrf2 were found to be more susceptible to TBI-induced ALI, as characterized by the higher increase in PCP, wet/dry weight ratio and alveolar cells apoptosis after TBI. This exacerbation of lung injury in Nrf2-deficient mice was associated with increased pulmonary mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); and with decreased pulmonary mRNA expression and enzymatic activities of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha1 (GST-alpha1)--as compared with their wild-type Nrf2 (+/+) counterparts after TBI. The results of the present study suggest that Nrf2 reduces TBI-induced acute lung injury, possibly by decreasing pulmonary inflammation and inducing antioxidant and detoxifying enzymes.
    Experimental Biology and Medicine 03/2009; 234(2):181-9. · 2.80 Impact Factor
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    ABSTRACT: Ketone bodies have been shown to be favorable alternative metabolic substrates and are protective under neuropathologies. At the same time, cytochrome c release has been reported following traumatic brain injury (TBI) and precipitates apoptosis via the mitochondrial pathway. The present study investigated the effects of a ketogenic diet (KD) on TBI. TBI was produced using the Feeney weight-drop model and the animals were fed either normal diet (ND) or KD. Brain edema was estimated by wet/dry weight ratio; cytochrome c was detected by Western blotting; cellular apoptosis in the penumbra area was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and active caspase-3 immunohistochemical staining. The results show that brain edema, cytochrome c release, and cellular apoptosis were induced after TBI and that KD reduced these changes dramatically. These findings suggest that KD has potential therapeutic benefit in TBI.
    Annals of clinical and laboratory science 02/2009; 39(1):76-83. · 0.88 Impact Factor
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    ABSTRACT: Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in modulating traumatic brain injury (TBI)-induced secondary brain injury. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. The absence of Nrf2 function in mice resulted in exacerbated brain injury as shown by the increased severity of neurological deficit, apoptosis, and brain edema at 24h after TBI. This exacerbation of brain injury in Nrf2-deficient mice was associated with increased mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and with decreased mRNA expression and enzymatic activity of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wild-type counterparts after TBI. In combination, these results suggest that Nrf2 plays an important role in protecting TBI-induced secondary brain injury, possibly by regulating inflammatory cytokines and inducing antioxidant and detoxifying enzymes.
    Journal of neurotrauma 02/2009; 26(1):131-9. · 4.25 Impact Factor
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    ABSTRACT: Acute lung injury (ALI) is a frequent but poorly understood complication of traumatic brain injury (TBI). The Nrf2-ARE pathway has been proved to be essential for protection against diffuse inflammation and oxidative damage, which are both involved in ALI following TBI. However, whether the Nrf2-ARE pathway is activated after TBI in the lung hasn't been studied. In the present study, the nuclear Nrf2 protein level was detected by Western blot and the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1), two Nrf2-regulated gene products, were determined by RT-PCR at 24 hours after TBI. In addition, the expression of Nrf2 and HO-1 was localized by immunohistochemical study. After TBI, the nuclear Nrf2 protein level in the lung was significantly increased and the mRNA levels of both HO-1 and NQO1 were also up-regulated. Moreover, immunohistochemical study showed that both Nrf2 and HO-1 were mainly localized in tracheobronchial epithelium and alveolar macrophages. These results suggest that the Nrf2-ARE pathway is activated in the lung after TBI.
    Brain Injury 10/2008; 22(10):802-10. · 1.51 Impact Factor

Publication Stats

275 Citations
75.97 Total Impact Points

Institutions

  • 2014
    • Nanjing University of Traditional Chinese Medicine
      Nan-ching, Jiangsu Sheng, China
  • 2010–2014
    • Nanjing Medical University
      • • Nanjing Medical University Eye Hospital
      • • Department of Neurosurgery
      Nan-ching, Jiangsu Sheng, China
    • Northeast Institute of Geography and Agroecology
      • Institute of Genetics and Developmental Biology
      Beijing, Beijing Shi, China
  • 2012
    • Chinese Academy of Sciences
      • State Key Laboratory of Molecular Developmental Biology
      Peping, Beijing, China
  • 2009–2012
    • Nanjing University
      • School of Medicine
      Nan-ching, Jiangsu Sheng, China