Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway.

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury.

The lymphatic system: a therapeutic target for central nervous system disorders.

The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis, metabolite clearance, and immune surveillance. The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology. They emerge as major pathways for fluid exchange. The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity. The lymphatic system, through its role in the clearance of neurotoxic proteins, autoimmune cell infiltration, and the transmission of pro-inflammatory signals, participates in the pathogenesis of a variety of neurological disorders, including neurodegenerative and neuroinflammatory diseases and traumatic injury. Vascular endothelial growth factor C is the master regulator of lymphangiogenesis, a process that is critical for the maintenance of central nervous system homeostasis. In this review, we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.

Utx Regulates the NF-κB Signaling Pathway of Natural Stem Cells to Modulate Macrophage Migration during Spinal Cord Injury.

Neural stem cells (NSCs) play vital roles in the homeostasis of neurological function. Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) is an important regulator of stem cell phenotypes. In our current study, we aimed to investigate whether the conditional knockout of UTX on neural stem cells alters macrophage assembly in response to spinal cord injury (SCI). Conditional knockout Utx of NSC (Utx-KO) mice was used to generate SCI models by the modified Allen method. We reported that neurological function and scar hyperplasia significantly improved in Utx-KO mice after SCI, accompanied by significantly reduced assembly of macrophages. With a 45-fold pathway array and Western blot, we found that Utx-KO could significantly inhibit NF-κB signaling activation and promote the synthesis and secretion of macrophage migration inhibitory factor (MIF) in NSCs. Administration of the selective NF-κB p65 activator betulinic acid and the selective MIF inhibitor ISO-1 confirmed that the activation of NF-κB p65 phosphorylation or inhibition of MIF could eliminate the benefits of Utx-KO in SCI, such as inhibition of macrophage aggregation and reduction in scar proliferation. This study confirmed that UTX in NSCs could alter macrophage migration and improve neurological function recovery after SCI in mice.

[Study on protective effect of water extract from Sabia parviflora on liver injury in mice induced by acetaminophen].

The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.

Silencing of lncRNA PKIA-AS1 Attenuates Spinal Nerve Ligation-Induced Neuropathic Pain Through Epigenetic Downregulation of CDK6 Expression.

Neuropathic pain (NP) is among the most intractable comorbidities of spinal cord injury. Dysregulation of non-coding RNAs has also been implicated in the development of neuropathic pain. Here, we identified a novel lncRNA, PKIA-AS1, by using lncRNA array analysis in spinal cord tissue of spinal nerve ligation (SNL) model rats, and investigated the role of PKIA-AS1 in SNL-mediated neuropathic pain. We observed that PKIA-AS1 was significantly upregulated in SNL model rats and that PKIA-AS1 knockdown attenuated neuropathic pain progression. Alternatively, overexpression of PKIA-AS1 was sufficient to induce neuropathic pain-like symptoms in uninjured rats. We also found that PKIA-AS1 mediated SNL-induced neuropathic pain by directly regulating the expression and function of CDK6, which is essential for the initiation and maintenance of neuroinflammation and neuropathic pain. Therefore, our study identifies PKIA-AS1 as a novel therapeutic target for neuroinflammation related neuropathic pain.

Geological significance of new zircon U-Pb geochronology and geochemistry: Niuxinshan intrusive complex, northern North China Craton.

The Huajian gold deposit is one of the largest hydrothermal intrusion-related gold deposits in eastern Hebei Province, located in the northern margin of the North China Craton (NCC). The mineralization in this district displays a close spatial association with the shoshonitic Niuxinshan intrusive complex (NIC), which contributes to the characterization of the metallogeny associated with convergent margin magmatism. In the current study, new geochronological and geochemical data are combined with previously published isotopic data, obtained from the granitic rocks in the NIC, to constrain the timing of the district's tectonic setting transformation and determine its bearing on regional metallogeny. The new geochronological data constrain the timing of the tectonic transformation between 155 and 185 Ma. The NIC's granitic rocks can be geochemically subdivided into two groups. One group's geochemical signature exhibits steep rare earth element (REE) patterns with negligible Eu anomalies, lower Yb, higher Sr, and negative Nb-Ta-Ti (NTT) anomalies, which indicate a volcanic-arc environment with a thickened crust in a convergent setting. The other group exhibits flat REE patterns with obvious negative Eu anomalies, higher Yb, lower Sr, and weak NTT anomalies, which indicate an intra-plate extensional environment with a thinning crust. Combining geochronologic and isotopic data, the mineralization is Late Jurassic (~155 Ma). This is interpreted to be genetically related to the crystallization of the shallow crustal-sourced portions of this complex. Additionally, a tectonic model is presented that provides a plausible explanation for the abundant polymetallic mineralization that occurs in the northern margin of the NCC after 155 Ma.

SOX2 knockdown inhibits the migration and invasion of basal cell carcinoma cells by targeting the SRPK1-mediated PI3K/AKT signaling pathway.

Basal cell carcinoma (BCC) is the most common type of human skin cancer, which is driven by the aberrant activation of Hedgehog signaling. Previous evidence indicated that sex determining region Y-box 2 (SOX2) is associated with the tumor metastasis. However, the expression and role of SOX2 in BCC remain unknown. Therefore, the aim of the current study was to analyze the possible mechanism of SOX2 in the progression of BCC. The levels of SOX2 in BCC cells were detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were also used to determine the migration and invasion of BCC cells. Immunoblotting and immunofluorescence were used for analyzing the role of SOX2 knockdown in the serine-arginine protein kinase 1 (SRPK1)-mediated phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in BCC cells. The results demonstrated that SOX2 is overexpressed in BCC tissues and cells. In addition, SOX2 knockdown inhibited the migration and invasion of BCC cells, and the epithelial-mesenchymal transition (EMT) progress of BCC cells. It was also observed that SOX2 knockdown decreased SRPK1 expression, which further led to the downregulation of PI3K and AKT expression levels in BCC cells. Furthermore, SRPK1 transfection or PI3K/AKT pathway activation abolished the inhibitory effects of SOX2 knockdown on the migration, invasion and EMT progress of BCC cells. In conclusion, these results indicated that SOX2 may potentially serve as a target for BCC therapy by targeting the SRPK1-mediated PI3K/AKT signaling pathway.

Sacroiliac joint tuberculosis: surgical management by posterior open-window focal debridement and joint fusion.

BACKGROUND: Sacroiliac joint tuberculosis(SJT) is relatively uncommon, but it may cause severe sacroiliac joint destruction and functional disorder. Few studies in the literature have been presented on SJT, reports of surgical treatment for SJT are even fewer. In this study, we retrospectively reviewed surgical management of patients with severe SJT of 3 different types and proposed to reveal the clinical manifestations and features and aim to determine the efficiency and security of such surgical treatment. METHODS: We reviewed 17 patients with severe SJT of 3 different types who underwent posterior open-window focal debridement and bone graft for joint fusion. Among them,five patients with anterior sacral abscess had anterior abscess curettage before debridement. Two patients with lumbar vertebral tuberculosis received one-stage posterior tuberculous debridement, interbody fusion and instrumentation. Follow-up was performed 36 months (26 to 45 months) using the following parameters: erythrocyte sedimentation rate(ESR), status of joint bony fusion on CT scan, visual analogue scale (VAS) and the Oswestry Disability Index (ODI). RESULTS: Buttock pain and low back pain were progressively relieved with time. 6 months later, pain was not obvious, and ESR resumed to normal levels within 3 months. Solid fusion of the sacroiliac joint occurred within 12 months in all cases. No complications or recurrence occurred. At final follow-up, all patients had no pain or only minimal discomfort over the affected joint and almost complete functional recovery. CONCLUSIONS: Posterior open-window focal debridement and joint fusion is an efficient and secure surgical method to treat severe SJT. If there is an abscess in the front of the sacroiliac joint, anterior abscess curettage should be performed as a supplement.

Tetramethylpyrazine Facilitates Functional Recovery after Spinal Cord Injury by Inhibiting MMP2, MMP9, and Vascular Endothelial Cell Apoptosis.

BACKGROUND: Spinal cord injury (SCI) is a major public health issue that leads to neurological dysfunctions and morbidities in patients. Tetramethylpyrazine (TMP) plays a neuroprotective role in SCI; however, the underlying mechanism has not been fully elucidated. OBJECTIVE: In the present study, we aimed to investigate the mechanisms and therapeutic effects of TMP on SCI. METHODS: A contusion SCI model was established that used a modified Allen's method. In the TMP group, TMP (200 mg/kg) was injected daily for 5 days post-injury, while in the Negative Control (NC) group, an equal volume of normal saline was injected. Hindlimb motor function was evaluated using the Basso, Beattie, Bresnahan (BBB) scale. The effects of TMP on protein levels of the matrix metalloproteinases 2 (MMP2) and 9 (MMP9), Bax and cleaved caspase-3 were determined by western blotting. Apoptotic changes in vascular endothelial cells were evaluated using immunofluorescence and TUNEL staining. Alterations in 3D vessel morphology after treatment with TMP were assessed by synchrotron radiation micro-CT (SRµCT). RESULTS: TMP treatment significantly improved recovery in hindlimb motor function and attenuated vascular endothelial cell apoptosis in rats with SCI. Additionally, TMP treatment markedly decreased the protein levels of MMP2 and MMP9, pro-apoptotic bax and cleaved caspase-3 while promoting angiogenesis, as evidenced by vessel visualization using SRµCT. CONCLUSION: These results indicate that TMP attenuated SCI-induced neurological impairments by the down-regulation of the expression of MMP2 and MMP9 proteins, the inhibition of vascular endothelial cell apoptosis, and the promotion of angiogenesis.

Modified O-T advancement flap for reconstruction of skin defects.

BACKGROUND: Round or oval defects are common in skin surgery. Functional and cosmetical reconstruction of defects in reparative process is critical for patients. Various flaps have been described, however, these flaps often result in longer scar or tip necrosis. To overcome these shortcomings, we modified O-T advancement flap on the basis of conventional O-T flap and observed the validity and complications during defect closure. MATERIALS AND METHODS: Defect transverse diameter was marked along the direction of minimum tension at the circular center. Extended line was drawn along defect transverse diameter with the same length of circular diameter. The skin was cut apart, and the flap was separated under the skin. Then the flap tips were sutured and fixed with the opposite center. After drainage, the defects were bandaged under compression. RESULTS: This study includes a total number of 48 patients. We examined the location and size of defect and postoperative clinical courses. The follow-up period was from 3 months to 1 year. Overall, 41 of 48 patients achieved the satisfactory postoperative effect. Recurrence and limb dysfunction complication was not observed, except 2 cases of wound scar, 3 cases of wound infect and 2 cases of flap tip necrosis. CONCLUSION: Modified O-T advancement flap is practical and safety. It overcomes the shortcomings of traditional O-T flap. Reconstruction of modified O-T flap is aesthetically acceptable.

Synchrotron radiation micro-CT as a novel tool to evaluate the effect of agomir-210 in a rat spinal cord injury model.

MicroRNA-210 (miR-210) was initially reported to be associated with hypoxia and plays a vital role in modulating angiogenesis. However, the potential effect and underlying mechanisms of miR-210 activity in rat spinal cord injury (SCI) have not yet been fully illuminated. In the present study, differential microRNA expression after SCI was determined by Microarray analysis. To explore the effect of miR-210 after SCI, we intrathecally injected agomir-210 with Alzet Osmotic Pumps to up-regulated the endogenous miR-210 expression. Then, synchrotron radiation micro-CT (SRµCT) imaging was used to investigate the effect of agomir-210 in rat SCI model. We found that the endogenous miR-210 expression could be up-regulated by intrathecal agomir-210 injection. The administration of agomir-210 significantly promoted angiogenesis, as evidenced by increased vessel number and volume detected by SRµCT, attenuated the lesion size and improved functional recovery after SCI. Additionally, agomir-210 attenuated cellular apoptosis and inflammation in the injured rat spinal cord. Expression levels of pro-apoptotic protein (Bax) and pro-inflammatory cytokines (TNF-α and IL-1ß) were significantly decreased after agomir-210 treatment, whereas expression levels of anti-apoptotic (Bcl-2) and anti-inflammatory (IL-10) proteins were up-regulated. In conclusion, our results indicated that SRµCT is a powerful imaging tool to evaluate the effects of angiogenesis after agomir-210 administration in rat SCI model. The up-regulation of endogenous miR-210 expression following agomir-210 administration promoted angiogenesis and anti-apoptotic protein expression, and attenuated inflammation. MiR-210 played a positive role in neurological functional recovery and could be a potential new therapeutic target for SCI.

Tetramethylpyrazine enhances functional recovery after contusion spinal cord injury by modulation of MicroRNA-21, FasL, PDCD4 and PTEN expression.

Our previous study showed Tetramethylpyrazine (TMP) has protective effects against SCI. In this study, we aimed to uncover the mechanism underlying the protective effects of TMP in SCI. SCI was induced in Sprague-Dawley rats with a modified weight-drop device. One group was subjected to SCI in combination with TMP administration at a dose of 200mg/kgd, for 3 days. Concurrently, another group received SCI in combination with an equal volume of 0.9% saline. Locomotor functional recovery was assessed during the 4 weeks post-injury by performing the Basso, Beattie, and Bresnahan (BBB) rating procedure. Lesion size and spared tissue were measured by cresyl violet staining. MicroRNA-21 (miR-21) expression was determined by real-time PCR and in situ hybridization. FasL, PDCD4, and PTEN are direct targets of miR-21 in many diseases and cell types; their levels were analyzed by western blot. Immunohistochemistry was performed to observe the expression of PDCD4 and PTEN. Cell apoptosis was assessed by TUNEL staining and DNA laddering. TMP treatment after contusion SCI significantly improved functional recovery, decreased lesion size, and increased tissue sparing and miR-21 levels; expression of FasL, PDCD4, and PTEN was decreased. TMP treatment also reduced apoptosis after SCI. Thus, TMP administration improved functional recovery and reduced cell apoptosis. Its protective effect may partly based on increasing the expression of miR-21 and decreasing the expression of FasL, PDCD4, and PTEN. These could serve as new exploratory targets for SCI treatment.

New isoindolinones from the fruiting bodies of Hericium erinaceum.

Hericium erinaceus is a well-known medicinal and edible mushroom, which is considered as a potential source to obtain antitumor candidates. In this work, five new isoindolinones, named erinaceolactams A-E (1-5), along with five known compounds (6-10), were isolated from 70% ethanol extract of the fruiting bodies of H. erinaceus. The structures of new compounds were validated by HRESIMS and 1D, 2D NMR. It's worth mentioning that there are two pairs of isomers included in the new compounds. Moreover, their cytotoxicity against metastatic human hepatocellular carcinoma cell lines SMMC-7221 and MHCC-97H were evaluated. The results showed that compounds 6 and 7 exhibited promising inhibitory potency against the growth of two cell lines.

Excision of apocrine glands with preservation of axillary superficial fascia for the treatment of axillary bromhidrosis.

BACKGROUND: Axillary bromhidrosis is a distressing problem, which has a strong negative effect on one's social life. OBJECTIVE: To evaluate the effects and complications of the surgical modality for the treatment of axillary bromhidrosis. METHODS: One hundred fifteen patients with axillary bromhidrosis were treated. Two incisions were made transversely along the marked lines on the axillary crease. Subdermal undermining of the marked area with a depth of 0.3 to 0.5 cm and transverse detachment were performed, allowing the exposure of the skin flaps. Skin flaps were carefully separated from the skin. The apocrine glands, follicles, and fats were dissected, and the axillary superficial fascia was maintained. RESULTS: All patients achieved good results in terms of malodor elimination during the follow-up period. All patients reported reduction in axillary sweating. Postoperative complications were minor, including small hematoma (3 cases), delayed wound healing (5 cases), pressure blister (5 cases), and slightly wound scar (2 cases). No infection, skin necrosis, malodor, or recurrence was observed. One hundred eleven patients (96.5%) were very satisfied and 4 (3.5%) patients satisfied with the procedure, with none regretful. CONCLUSION: The procedure has the advantage of a high success rate in radical elimination of the malodor with minor complications.

Anterior cervical discectomy with arthroplasty versus anterior cervical discectomy and fusion for cervical spondylosis.

This meta-analysis aims to estimate the benefits and drawbacks associated with anterior cervical discectomy with arthroplasty (ACDA) versus anterior cervical discectomy and fusion (ACDF) for cervical spondylosis. Of 3651 identified citations, 10 randomised controlled studies involving 2380 participants were included. Moderate quality evidence supports that patients in the ACDA group had: (1) a higher Neck Disability Index (NDI) success rate at 3 month (relative risk [RR]=0.85, 95% confidence interval [CI] 0.78 to 0.93, p=0.0002) and 2 year follow-up (RR=0.95, 95%CI 0.91 to 1.00, p=0.04); (2) greater neurological success at 2 year follow-up (RR=0.95, 95%CI 0.92 to 0.98); and (3) were more likely to be employed within 6 weeks after surgery (RR=0.80 95%CI 0.66 to 0.96). In summary, the current evidence indicates that ACDA is associated with a higher NDI success rate in the short and long-term as well as a higher neurological success rate. Patients who undergo ACDA may also have a greater likelihood of being employed in the short-term. However, all of the evidence reviewed is of moderate or low quality and the clinical significance often marginal or unclear. Additional data are needed to compare the benefits and limitations of ACDA and ACDF.

Development of biodegradable polycaprolactone film as an internal fixation material to enhance tendon repair: an in vitro study.

BACKGROUND: Current tendon repair techniques do not provide sufficient tensile strength at the repair site, and thus early active motion rehabilitation after tendon repair is discouraged. To enhance the post-operative tensile strength, we proposed and tested an internal fixation technique using a polycaprolactone (PCL) biofilm. PCL was chosen for its good biocompatibility, excellent mechanical strength, and an appropriate degradation time scale. METHODS: PCL biofilms were prepared by a modified melt-molding/leaching technique, and the physical and mechanical properties and in vitro degradation rate were assessed. The pore size distribution of the biofilm and the paratenon of native tendons were observed using scanning electron microscopy. Next, we determined whether this biofilm could enhance the tensile strength of repaired tendons. We performed tensile tests on rabbit Achilles tendons that were first lacerated and then repaired: 1) using modified Kessler suture combined with running peripheral suture ('control' group), or 2) using biofilm to wrap the tendon and then fixation with sutures ('biofilm' group). The influence of different repair techniques on tendon tensile strength was evaluated by mechanical testing. RESULTS: The novel biofilm had supple texture and a smooth surface. The mean thickness of the biofilm was 0.25 mm. The mean porosity of the biofilm was 45.3%. The paratenon of the rabbit Achilles tendon had pores with diameters ranging from 1 to 9 µm, which were similar to the 4-12 µm diameter pores in the biofilm cross-section. The weight loss of the biofilms at 4 weeks was only 0.07%. The molecular weight of PCL biofilms did not change after immersion in phosphate buffered saline for 4 weeks. The failure loads of the biofilm were similar before (48 ± 9 N) and after immersion (47 ± 7 N, P > 0.1). The biofilm group had ~70% higher mean failure loads and 93% higher stiffness compared with the control group. CONCLUSIONS: We proposed and tested an internal fixation technique using a PCL biofilm to enhance tendon repair. Internal fixation with the biofilm followed by standard suturing can significantly increase the tensile strength of tendon repair sites. This technique has the potential to allow active motion rehabilitation during the early post-operative period.

Anti-apoptotic effect of microRNA-21 after contusion spinal cord injury in rats.

Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). Dysregulation of microRNAs (miRNAs) has been found following SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. We analyzed the miRNA expression patterns 1 and 3 days following rat SCI using miRNA microarray. Microarray data revealed that nine miRNAs were upregulated and five miRNAs were downregulated 1 day post-injury, and that three miRNAs were upregulated and five miRNAs were downregulated 3 days post-injury, in the sites of contused when compared with sham rat spinal cords. Because miR-21 was one of the miRNAs being most significantly upregulated, we investigated its function. Knockdown of miR-21 by antagomir-21 led to attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing in rats. Compared with the negative control group, treatment with antagomir-21 significantly increased apoptosis following SCI. Pro-apoptosis genes Fas ligand (FasL), phosphatase and tensin homolog (PTEN), and programmed cell death protein 4 (PDCD4) were proved to be direct targets of miR-21 in many diseases and cell types. In vivo treatment with antagomir-21 increased the expression of FasL and PTEN, but did not affect PDCD4. These results suggested that miR-21 played an important role in limiting secondary cell death following SCI, and that the protective effects of miR-21 might have been the result of its regulation on pro-apoptotic genes. Thus, miR-21 may play an important role in the pathophysiology of SCI.

Tetramethylpyrazine accelerates the function recovery of traumatic spinal cord in rat model by attenuating inflammation.

In the present study, we explored the effects of tetramethylpyrazine (TMP), an alkaloid extracted from the Chinese herbal medicine Ligusticum wallichii Franchat (chuanxiong), on a rat model of contusion spinal cord injury (SCI). The contusion SCI model was induced in rats by a modified Allen's weight-drop method with a severity of 5 g × 50 mm impacting on the T10 segment. In the TMP treatment group, rats were injected intraperitoneally (i.p.) with TMP (200mg/kg), every 24h for 5 days, starting half an hour after contusion SCI. The control group was treated with saline. Compared with the control group, the TMP group significantly ameliorated the recovery of hindlimb function of rats. TMP treatment significantly reduced the expression of macrophage migration inhibitory factor, nuclear factor κappa B, pro-inflammatory cytokine interleukin-18 and neutrophil infiltration. On the other hand, TMP enhanced the expression of inhibitor κappa B and anti-inflammation cytokine interleukin-10. In conclusion, our results demonstrate that TMP inhibits the development of inflammation and tissue injury associated with spinal cord contusion in rats which may improve the rats' hindlimb function.