Feasibility of Brain Imaging Using a Digital Surround Technology Body Coil: A Study Based on SRGAN-VGG Convolutional Neural Networks.

Brain imaging using conventional head coils presents several problems in routine magnetic resonance (MR) examination, such as anxiety and claustrophobic reactions during scanning with a head coil, photon attenuation caused by the MRI head coil in positron emission tomography (PET)/MRI, and coil constraints in intraoperative MRI or MRI-guided radiotherapy. In this paper, we propose a super resolution generative adversarial (SRGAN-VGG) network-based approach to enhance low-quality brain images scanned with body coils. Two types of T1 fluid-attenuated inversion recovery (FLAIR) images scanned with different coils were obtained in this study: joint images of the head-neck coil and digital surround technology body coil (H+B images) and body coil images (B images). The deep learning (DL) model was trained using images acquired from 36 subjects and tested in 4 subjects. Both quantitative and qualitative image quality assessment methods were performed during evaluation. Wilcoxon signed-rank tests were used for statistical analysis. Quantitative image quality assessment showed an improved structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) in gray matter and cerebrospinal fluid (CSF) tissues for DL images compared with B images (P <.01), while the mean square error (MSE) was significantly decreased (P <.05). The analysis also showed that the natural image quality evaluator (NIQE) and blind image quality index (BIQI) were significantly lower for DL images than for B images (P <.0001). Qualitative scoring results indicated that DL images showed an improved SNR, image contrast and sharpness (P<.0001). The outcomes of this study preliminarily indicate that body coils can be used in brain imaging, making it possible to expand the application of MR-based brain imaging.

Follow-up study of high-dose praziquantel therapy for cerebral sparganosis.

BACKGROUND: Cerebral sparganosis is the most serious complication of human sparganosis. Currently, there is no standard for the treatment of inoperable patients. Conventional-dose praziquantel therapy is the most reported treatment. However, the therapeutic outcomes are not very effective. High-dose praziquantel therapy is a useful therapeutic choice for many parasitic diseases that is well tolerated by patients, but it has not been sufficiently evaluated for cerebral sparganosis. This study aims to observe the prognoses following high-dose praziquantel therapy in inoperable patients and the roles of MRI and peripheral eosinophil absolute counts during follow-up. METHODOLOGY: Baseline and follow-up epidemiological, clinical, radiological and therapeutic data related to 10 inoperable patients with cerebral sparganosis that were treated with repeated courses of high-dose praziquantel therapy, with each course consisting of 25 mg/kg thrice daily for 10 days were assessed, followed by analyses of the prognoses, MRI findings and peripheral eosinophil absolute counts. PRINCIPAL FINDINGS: Baseline clinical data: the clinical symptoms recorded included seizures, hemiparesis, headache, vomiting and altered mental status. Peripheral blood eosinophilia was found in 3 patients. The baseline radiological findings were as follows. Motile lesions were observed in 10 patients, including aggregated ring-like enhancements, tunnel signs, serpiginous and irregular enhancements. Nine of the 10 patients had varying degrees of white matter degeneration, cortical atrophy and ipsilateral ventricle dilation. The follow-up clinical data were as follows. Clinical symptom relief was found in 8 patients, symptoms were eliminated in 1 patient, and symptoms showed no change from baseline in 1 patient. Peripheral blood eosinophilia was found in 2 patients. The follow-up radiological findings were as follows. Motile lesions that were transformed into stable, chronic lesions were found in 8 patients, and motile lesions that were eliminated completely were found in 2 patients. CONCLUSIONS: High-dose praziquantel therapy for cerebral sparganosis is effective. The radiological outcomes of motile lesions are an important indicator during the treatment process, especially during follow-ups after clinical symptoms have improved. Peripheral eosinophil absolute counts cannot be used as an effective prognostic indicator.

Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells.

Chlorotoxin (CTX) is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which inhibits low-conductance chloride channels in colonic epithelial cells. It has been reported that CTX also binds to matrix metalloproteinase-2 (MMP-2), membrane type-1 MMP, and tissue inhibitor of metalloproteinase-2, as well as CLC-3 chloride ion channels and other proteins. Pancreatic cancer cells require the activation of MMP-2 during invasion and migration. In this study, the fusion protein was generated by joining the CTX peptide to the amino terminus of the human IgG-Fc domain without a hinge domain, the monomeric form of chlorotoxin (M-CTX-Fc). The resulting fusion protein was then used to target pancreatic cancer cells (PANC-1) in vitro. M-CTX-Fc decreased MMP-2 release into the media of PANC-1 cells in a dose-dependent manner. M-CTX-Fc internalization into PANC-1 cells was observed. When the cells were treated with chlorpromazine (CPZ), the internalization of the fusion protein was reduced, implicating a clathrin-dependent internalization mechanism of M-CTX-Fc in PANC-1 cells. Furthermore, M-CTX-Fc clearly exhibited the inhibition of the migration depending on the concentration, but human IgG, as negative control of Fc, was not affected. The M-CTX-Fc may be an effective instrument for targeting pancreatic cancer.

The value and limitations of contrast-enhanced transrectal ultrasonography for the detection of prostate cancer.

OBJECTIVES: To evaluate the role of contrast-enhanced transrectal ultrasonography (CE-TRUS) for detecting prostate carcinoma. METHODS: Sixty-five patients with elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) were assessed using transrectal ultrasound (TRUS) and CE-TRUS. In all the patients, CE-TRUS was performed with intravenous injection of contrast agent (SonoVue, 2.4 ml) before biopsy. The cancer detection rates of the two techniques were compared. False-positive and false-negative findings related to CE-TRUS were analyzed in comparison to the pathological results of biopsy or radical prostatectomy. The targeted biopsy to abnormal CE-TRUS areas was also compared to systematic biopsy. RESULTS: Prostate cancer was detected in 29 of the 65 patients. CE-TRUS showed rapid focal enhancement or asymmetric vessels of peripheral zones in 28 patients; 23 of them had prostate cancer. CE-TRUS had 79.3% sensitivity, compared to 65.5% of TRUS (P<0.05). There were five false-positive and six false-negative findings from CE-TRUS. Benign prostate hyperplasia, and acute and chronic prostatitis were important causes related to the false-positive results of CE-TRUS. Prostate cancer originating from the transition zone or peripheral zone with lower PSA levels, small-size foci, and moderately or well-differentiated tumor was missed by CE-TRUS. The cancer detection rate of targeted biopsy (75%, 33/44 cores) was significantly higher than one of systematic biopsy (48.2%, 162/336) in those 28 cases (P<0.05). In addition, no significant correlation was found between the cancer detection rate with CE-TRUS and serum PSA levels. CONCLUSION: CE-TRUS may improve the detection rate of prostate cancer through targeted biopsy of contrast-enhanced abnormalities. Our findings indicate that systematic biopsies should not be eliminated on the basis of false-positive and false-negative findings related to CE-TRUS.

[Influence of nuclear factor erythroid 2-related factor 2 genotype on tumor necrosis factor-α and metalloproteinase-9 expression in spinal cord after spinal cord injury in mice].

OBJECTIVE: To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) as a key transcription factor of cytoprotection against inflammation in the spinal cord upregulation of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α(TNF-α) after spinal cord injury (SCI). METHODS: Wild-type Nrf2(+/+) and Nrf2(-/-)-deficient mice were subjected to a murine SCI model induced by the application of vascular clips (force of 10 g) to the dura after a three-level T8-T10 laminectomy. The wet/dry weight ratio was used to reflect the percentage of water content of impaired spinal cord tissue at 48 h after SCI. The mRNA levels of MMP-9 were determined using reverse-transcriptase polymerase chain reaction (RT-PCR), and the protein levels of TNF-α and MMP-9 were detected by enzyme-linked immunosorbent assay at 24 h after SCI. Furthermore, gelatin zymography analysis was used to show MMP-9 activity of spinal cord tissue at 24 h after SCI. Software SPSS 16.0 was used for the statistical analysis. RESULTS: After SCI, spinal cord water content, the expression of TNF-α and MMP-9 all increased in both injured Nrf2(+/+) and Nrf2(-/-) mice compared with their respective sham-operated mice. However, Nrf2(-/-) mice were shown to have more severe spinal cord edema, more TNF-α expression, more production and activity of MMP-9 compared with their wild-type Nrf2(+/+) counterparts after SCI (P < 0.05). CONCLUSIONS: The results suggest that Nrf2 plays an important protective role in limiting the spinal cord upregulation of TNF-α and MMP-9 after SCI. It may be a new therapeutic target of SCI.

Sulforaphane attenuates matrix metalloproteinase-9 expression following spinal cord injury in mice.

Inflammation plays an important role in the pathogenesis of secondary damage after spinal cord injury (SCI). The present study explored the effect of sulforaphane (SFN), a potent anti-inflammatory extract of cruciferous vegetables, on the expression of two inflammatory mediators, metalloproteinase (MMP)-9 and TNF-α, in a murine model of SCI. Murine spinal cord injury was induced by the application of vascular clips (force of 10 g) to the dura after a three-level T8-T10 laminectomy. The wet/dry weight ratio was used to reflect the percentage of water content of impaired spinal cord tissue at 48 hr after SCI. The mRNA levels of MMP-9 were determined using the reverse-transcriptase polymerase chain reaction (RT-PCR), and protein levels of TNF-α and MMP-9 were detected by enzyme-linked immunosorbent assays (ELISA) at 24 hr after SCI. Gelatin zymography was used to determine MMP-9 activity of spinal cord tissue at 24 hr after SCI. Mice treated with SFN at 1 hr after SCI had lower expression and activity of MMP-9 compared to mice with SCI. The decrease of MMP-9 in mice treated with SFN was associated with decreased levels of spinal cord water content and TNF-α. In summary, suforaphane decreases MMP-9 and TNF-α expression and vascular permeability changes following spinal cord injury in mice.

Peroxisome proliferator-activated receptor gamma agonist rosiglitazone attenuates oxyhemoglobin-induced Toll-like receptor 4 expression in vascular smooth muscle cells.

Inflammation and immune response have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Recently, increased TLR4 expression has been associated with the development of cerebral vasospasm in a rabbit model of SAH. Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, effective inhibitors of TLR4 activation, may modulate the vasospasm progression via their anti-inflammation effects. We investigate whether the blood component oxyhemoglobin (OxyHb) can induce the expression of Toll-like receptor (TLR) 4 in vascular smooth muscle cells (VSMCs), and evaluate the modulatory effects of PPARgamma agonist rosiglitazone on OxyHb-induced inflammation in VSMCs. Cultured VSMCs incubated with or without rosiglitazone were exposed to OxyHb at 10muM for up to 48h. Expression of TLR4 was assessed by immunocytochemistry and Western blot analysis. Production of tumor necrosis factor alpha (TNF-alpha) in conditioned medium were quantified by ELISA. A marked increase of TLR4 production and TNF-alpha release was observed at 48h after cells were treated with OxyHb. Rosiglitazone reduced TLR4 immunocytochemistry staining and protein production significantly in VSMCs. A specific antagonist for PPARgamma, GW9662, could reverse the anti-inflammatory effects of rosiglitazone. The results demonstrated that OxyHb exposure could induce TLR4 activation in cultured VSMCs. Rosiglitazone suppressed TLR4 expression and cytokine release via the activation of PPARgamma and may have a therapeutic potential for the treatment of vasospasm following SAH.

Genistein, a soybean isoflavone, reduces the production of pro-inflammatory and adhesion molecules induced by hemolysate in brain microvascular endothelial cells.

Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean that exhibits an anti-inflammatory effect. The present study was designed to examine the effects of genistein on expression levels of hemolysate-induced proinflammatory and adhesion molecules in SD rat brain microvascular endothelial cells (BMECs). Genistein treatment attenuated hemolysate-induced nuclear factor-kappa B (NF-kappaB) p65 translocation in BMECs. In addition, genistein suppressed the expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). The inhibitory rate of 50 pM genistein for TNF-alpha, MCP-1 and ICAM-1 was 65.4%, 60.5% and 54.9% respectively. These inhibitory effects of genistein on proinflammatory and adhesion molecules were not due to decreased BMEC viability as assessed by MTT test. Taken together the present study suggests that genistein suppresses expression levels of hemolysate-induced pro-inflammatory and adhesion molecules in cerebral endothelial cells.

The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats.

BACKGROUND: The ketogenic diet (the KD) is an effective treatment for intractable epilepsy, especially in the paediatric population, and a growing number of studies have shown the neuroprotective role of the KD. However, few studies focused on the neuroprotective effects of the KD in traumatic brain injury (TBI). The present study aimed to investigate the effects of the KD on TBI. METHODS AND PROCEDURES: Male Sprague-Dawley rats (n = 60) were randomly divided into four groups according to the diet fed (the KD vs normal diet) and whether brain was injured or not. TBI was produced using Feeney weight drop model. Brain oedema was estimated by wet/dry weight ratio; Bax and Bcl-2 mRNA levels were determined by RealTime-PCR; Bax and Bcl-2 protein levels were detected by Western blot. Furthermore, cellular apoptosis in the penumbra area was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. MAIN OUTCOMES AND RESULTS: The results indicated that both Bax mRNA and protein levels were significantly elevated 72 hours after TBI and decreased by KD administration. Neither TBI nor the KD affected Bcl-2 mRNA and protein levels. KD administration also reduced brain oedema and cellular apoptosis. CONCLUSION: These results suggest that the KD might be a useful treatment for children suffering from the consequences of TBI.

Transcription factor Nrf2 plays a pivotal role in protection against traumatic brain injury-induced acute intestinal mucosal injury in mice.

BACKGROUND: Traumatic brain injury (TBI) can induce an acute intestinal mucosal injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a unique role in many physiological stress processes, but its contribution to intestinal mucosal injury after TBI remains to be determined. MATERIALS AND METHODS: Wildtype Nrf2 (+/+) and Nrf2 (-/-) deficient mice were subjected to a moderately severe weight-drop impact head injury. Intestinal mucosal morphological changes, plasma endotoxin, intestinal permeability, apoptosis, inflammatory cytokines, and antioxidant/detoxifying enzymes were measured at 24 hours after TBI. RESULTS: Nrf2 deficient mice were found to be more susceptible to TBI-induced acute intestinal mucosal injury, as characterized by the higher increase in gut structure damage, plasma endotoxin, intestinal permeability, and apoptosis after TBI. This exacerbation of intestinal mucosal injury in Nrf2 deficient mice was associated with increased intestinal mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta and interleukin-6, and with decreased intestinal mRNA expression and activity levels of antioxidant and detoxifying enzymes including NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wildtype Nrf2 (+/+) counterparts after TBI. CONCLUSIONS: We show for the first time that mice lacking Nrf2 are more susceptible to TBI-induced acute intestinal mucosal injury. Our data suggests that Nrf2 plays an important role in protecting TBI-induced intestinal mucosal injury, possibly by regulating of inflammatory cytokines and inducing of antioxidant and detoxifying enzymes.

Expression of monocyte chemoattractant protein-1 in the cerebral artery after experimental subarachnoid hemorrhage.

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an important role in the recruitment of macrophages. Although previous studies have demonstrated that MCP-1 has been shown to be involved in the damaging inflammatory processes associated with stroke, infection, neoplasia, and others in the central nervous system, the role of MCP-1 in the cerebral artery after experimental subarachnoid hemorrhage (SAH) in rats has been largely unexplored. This study was undertaken to investigate the expression of the MCP-1 in SAH model and to clarify the potential role of MCP-1 in cerebral vasospasm. A total of 80 rats were randomly divided into four groups: control group; day 3, day 5, and day 7 groups. Day 3, day 5, and day 7 groups were all SAH groups. The animals in day 3, day 5 and day 7 groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the MCP-1 expression was assessed by real-time PCR, Western blot and immunohistochemistry. The cross-sectional area of basilar artery was found to be 85,373+/-8794 mum(2) in control group, 59,210+/-7281 mum(2) in day 3, 50,536+/-6519 mum(2) in day 5, and 66,360+/-7452 mum(2) in day 7, respectively. The basilar arteries exhibited vasospasm after SAH and became more severe on day 5. The elevated mRNA and protein of MCP-1 were detected after SAH and peaked on day 5. MCP-1 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH and these findings might have important implications during the administration of specific MCP-1 antagonists in order to prevent or reduce cerebral vasospasm caused by SAH.

Hemangiopericytomas in the central nervous system.

Hemangiopericytomas, which are more aggressive than meningiomas, are rare in the central nervous system (CNS). We analyzed the clinical, radiological and histological features and treatment of 26 patients with hemangiopericytomas in the CNS. The ratio of male to female patients was 1:1. Most tumors were located in the parasagittal and falx regions. The tumors were dense or mixed as assessed by CT scans, and most were homogeneously enhanced. Most tumors were isointense on T1-weighted MRI, and high or mixed intensity on T2-weighted MRI; they were homogeneously or heterogeneously enhanced. Histological examination indicated numerous small vascular spaces in the tumor. All tumors were immunohistochemically positive for vimentin. All patients were treated with surgery, and some of them underwent subsequent radiotherapy. The recurrence rate for hemangiopericytoma in this study was high. Our observations suggest that the biological behavior of hemangiopericytoma differs markedly from that of meningioma. Surgical removal and post-operative radiotherapy are thus critical for the treatment of this tumor.

Influence of Nrf2 genotype on pulmonary NF-kappaB activity and inflammatory response after traumatic brain injury.

Inflammatory response plays an important role in the pathogenesis of acute lung injury (ALI) after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study explored the influence of Nrf2 genotype on the production of cytokines and on activation of transcription factors in a murine TBI model. Wild-type Nrf2 (+/+) and Nrf2 (-/-) deficient mice were subjected to a moderately severe weight-drop impact-acceleration head injury. Lung wet/dry weight ratio, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor kapp-aB (NF-kappaB) were investigated at 24 hr after TBI. Nrf2 (-/-) mice were shown to have a greater increase in the lung wet/dry weight ratio compared to their wild-type Nrf2 (+/+) counterparts after TBI. This exacerbation of lung injury in Nrf2 (-/-) mice was associated with increased levels of TNF-alpha, IL-1beta, IL-6, ICAM-1, and their mediator, NF-kappaB. The results suggest that Nrf2 plays an important protective role in attenuating the pulmonary inflammatory response and NF-kappaB activation after TBI.

Potential contribution of nuclear factor-kappaB to cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

Nuclear factor-kappaB (NF-kappaB) plays a key role in inflammation, which is involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study, we assessed the potential role of NF-kappaB in regulation of cerebral vasospasm. Nuclear factor-kappaB DNA-binding activity was measured in cultured vascular smooth muscle cells (VSMCs) treated with hemolysate and pyrrolidine dithiocarbamate (PDTC, 80 micromol/L), an inhibitor of NF-kappaB. Forty-two rabbits were divided into three groups: control, SAH, and PDTC groups (n=14 for each group). The caliber of the basilar artery was evaluated. Nuclear factor-kappaB DNA-binding activity and the gene expression levels of cytokines and adhesion molecules in the basilar artery were measured. Immunohistochemical study was performed to assess the expression and localization of tumor necrosis factor (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase (MPO). It was observed that NF-kappaB DNA-binding activity was significantly increased by treatment with hemolysate in cultured VSCMs, but this increase was suppressed by pretreatment with PDTC. Severe vasospasm was observed in the SAH group, which was attenuated in the PDTC group. Subarachnoid hemorrhage could induce increases of NF-kappaB DNA-binding activity and the gene expression levels of TNF-alpha, interleukin (IL)-1 beta, ICAM-1, and vascular cell adhesion molecule (VCAM)-1, which were reduced in the PDTC group. Immunohistochemical study demonstrated that the expression levels of TNF-alpha, ICAM-1, and MPO were all increased in the SAH group, but these increases were attenuated in the PDTC group. Our results suggest that NF-kappaB is activated in the arterial wall after SAH, which potentially leads to vasospasm development through induction of inflammatory response.

Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats.

AIM: Nuclear factor kappa B (NF-kappaB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-kappaB is activated and intercellular adhesion molecule-1 (ICAM-1) expressed in the gut following traumatic brain injury (TBI). The aim of current study was to investigate the temporal pattern of intestinal NF-kappaB activation and ICAM-1 expression following TBI. METHODS: Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-kappaB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples. RESULTS: There was a very low NF-kappaB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-kappaB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase) and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-kappaB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI. CONCLUSION: TBI could induce an immediate and persistent up-regulation of NF-kappaB activity and subsequent up-regulation of ICAM-1 expression in the intestine. Inflammatory response mediated by increased NF-kappaB activation and ICAM-1 expression may play an important role in the pathogenesis of acute gut mucosal injury following TBI.

Effect of systemic LPS injection on cortical NF-kappaB activity and inflammatory response following traumatic brain injury in rats.

The aim of current study is to investigate the effect of systemic administration of lipopolysaccharide (LPS) on the temporal pattern of cortical nuclear factor kappa B (NF-kappaB) binding activity, inflammatory response and secondary damage in the injured brain following traumatic brain injury (TBI). Right parietal cortical contusion in rats was made by using weight-dropping method. The rats were randomly divided into sham, LPS, TBI and TBI-LPS groups, with LPS injected intraperitoneally. NF-kappaB binding activity, cytokines, intercellular adhesion molecule-1 (ICAM-1) and brain damage were detected by electrophoretic mobility shift assay (EMSA), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labeling (TUNEL) apoptosis, respectively. The results showed that systemic administration of LPS following TBI could induce an immediate, strong and persistent upregulation of NF-kappaB, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and ICAM-1 in the area surrounding the injured brain. As compared with rats of sham, LPS and TBI groups, NF-kappaB binding activity, TNF-alpha and IL-6 were significantly upregulated in the surrounding cortex of injured site as early as 3 h postinjury when challenged with LPS, kept at high level up to 7-days postinjury. ICAM-1-positive vessels and apoptotic TUNEL-positive cells in the injured brain were also significantly increased in TBI-LPS rats. It was concluded that inflammatory response and secondary brain damage occurred in the injured brain could be highly exacerbated by endotoxemia.

Levels of vasoactive intestinal peptide, cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction.

AIM: To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction. METHODS: Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VIP in jejunum. RESULTS: Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8+/-29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7+/-34.1 ng/L, 148.7+/-22.8 ng/L, 132.8+/-21.6 ng/L, respectively), but significantly increased at 72 h (405.0+/-29.8 ng/L) and markedly declined on d 7 (130.7+/-19.3 ng/L). However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBI (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6+/-1.4 ng /g; CGRP, 70.6+/-17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4+/-5.0 ng/g; CGRP, 103.8+/-22.1 ng/g), and declined gradually at 12 h and 24 h (VIP, 16.5+/-1.8 ng/g, 5.5+/-1.4 ng/g; CGRP, 34.9+/-9.7 ng/g, 18.5+/-7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7+/-9.5 ng/g; CGRP, 142.1+/-24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8+/-1.1 ng/g; CGRP, 102.5+/-18.1 ng/g). The CCK levels in jejunum were found to change in a similar trend as that in plasma with the concentrations of CCK significantly increased following TBI (99-517% increases) and peaked at 72 h. CONCLUSION: Traumatic brain injury can lead to significant changes of brain-gut peptides in both plasma and small intestine, which may be involved in the pathogenesis of complicated gastrointestinal dysfunction.