Granulocyte-macrophage colony-stimulating factor (GM-CSF) shows therapeutic effect on dimethylnitrosamine (DMN)-induced liver fibrosis in rats.

This study was undertaken to investigate the inhibitory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Liver fibrosis was induced in Sprague-Dawley rats by injecting DMN intraperitoneally (at 10 mg/kg of body weight) daily for three consecutive days per week for 4 weeks. To investigate the effect of GM-CSF on disease onset, GM-CSF (50 µg/kg of body weight) was co-treated with DMN for 2 consecutive days per week for 4 weeks (4-week groups). To observe the effect of GM-CSF on the progression of liver fibrosis, GM-CSF was post-treated alone at 5-8 weeks after the 4 weeks of DMN injection (8-week groups). We found that DMN administration for 4 weeks produced molecular and pathological manifestations of liver fibrosis, that is, it increased the expressions of collagen type I, alpha-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1), and decreased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. In addition, elevated serum levels of aspartate aminotransferase (AST), total bilirubin level (TBIL), and decreased albumin level (ALB) were observed. In both the 4-week and 8-week groups, GM-CSF clearly improved the pathological liver conditions in the gross and histological observations, and significantly recovered DMN-induced increases in AST and TBIL and decreases in ALB serum levels to normal. GM-CSF also significantly decreased DMN-induced increases in collagen type I, α-SMA, and TGF-ß1 and increased DMN-induced decreases in PPAR-γ expression. In the DMN groups, survival decreased continuously for 8 weeks after DMN treatment for the first 4 weeks. GM-CSF showed a survival benefit when co-treated for the first 4 weeks but a marginal effect when post-treated for 5-8 weeks. In conclusion, co-treatment of GM-CSF showed therapeutic effects on DMN-induced liver fibrosis and survival rates in rats, while post-treatment efficiently blocked liver fibrosis.

Impact of prognostic nutritional index on the recurrence of hepatocellular carcinoma after a curative resection.

BACKGROUNDS/AIMS: The purpose of this retrospective study was to determine the association between prognostic nutritional index (PNI) and recurrence of hepatocellular carcinoma after a curative resection. METHODS: Between 2007 to 2019, 130 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. PNI was calculated. Its cutoff value was identified through receiver operating characteristic curve analysis. According to PNI, patients were divided into two groups. Univariate and multivariate analyses were performed to identify independent risk factors for recurrence. RESULTS: The cutoff value of PNI was 52. In univariate analysis, alcoholic liver cirrhosis (p = 0.041), protein induced by vitamin K antagonist- II ≥ 200 (p = 0.012), indocyanine green retention test (ICG R15) >10% (p = 0.001), estimated blood loss ≥ 800 mL (p = 0.037), tumor size (p = 0.001), microvascular invasion (p = 0.023), T-stage (p = 0.001), and PNI < 52 (p = 0.001) were significant factors affecting the recurrence. In multivariate analysis, alcoholic liver cirrhosis (p = 0.046), ICG R15 >10% (p = 0.025), T-stage (p = 0.003), and PNI < 52 (p = 0.046) were independent prognostic factors for disease-free survival. CONCLUSIONS: PNI, a nutritional and immunologic factor, is an independent prognostic factor that can predict the recurrence of hepatocellular carcinoma in patients undergoing a curative resection.

Timing for Introduction of Total Laparoscopic Living Donor Right Hepatectomy; Initial Experience Based on the Data of Laparoscopic Major Hepatectomy.

BACKGROUND: This study evaluated the timing of safe introduction of total laparoscopic donor right hepatectomy (TLDRH) based on outcomes of laparoscopic major hepatectomy (LMH). METHODS: The data of 1013 consecutive patients who underwent laparoscopic liver resection from 2003 to 2017 were reviewed; the cumulative sum method was used to evaluate the learning curve of LMH. Patients were divided into 3 groups according to the timing of introduction of TLDRH (since 2010) and learning curve of LMH. Surgical outcomes of LMH and TLDRH were evaluated. RESULTS: Cumulative sum analysis demonstrated a learning curve of approximately 73 cases of LMH. In phase I (before the introduction of TLDRH, 2003-2009), 38 cases of LMH were performed. Phase II (after the introduction of TLDRH until learning curve of LMH, 2010-2014), 35 and 15 cases of LMH and TLDRH were performed, respectively. Phase III (after learning curve of LMH until 2017, 2014-2017), 59 and 20 cases of LMH and TLDRH were performed, respectively. In cases of LMH, there was significant improvement in the operation time 398.9 ± 140.9 versus 403.7 ± 165.2 versus 265.5 ± 91.7; P < 0.001), estimated blood loss (1122.9 ± 1460.2 versus 1209.3 ± 1409.1 versus 359.8 ± 268.8; P < 0.001), and open conversion rate (26.3% versus 22.9% versus 13.6%; P = 0.026) between phases I versus II versus III. In cases of TLDRH, the operation time (567.8 ± 117.9 versus 344.2 ± 71.8; P < 0.001), estimated blood loss (800.7 ± 514.8 versus 439.4 ± 347.0; P = 0.004), and hospital stay (12.5 ± 4.36 versus 9.15 ± 4.84; P = 0.025) significantly improved in phase III. CONCLUSIONS: Overcoming the learning curve of LMH before starting TLDRH is advisable to ensure donor's surgical outcomes.

Feasibility of Solo Single-Incision Laparoscopic Surgery in Non-anatomical Minor Liver Resection: a Propensity Score-Matched Analysis.

BACKGROUND: We introduced solo surgery using a laparoscopic scope holder to wide an operator's activity range and reduce instrument crowding and clashing in single incisional surgery. This study aimed to compare the surgical outcomes of solo single-incision laparoscopic surgery (SILS) and conventional multiport laparoscopic surgery (MULS) for hepatocellular carcinoma (HCC). METHODS: Among 477 consecutive patients between January 2004 and December 2017, 214 patients were included. To overcome selection bias, we performed 1:1 match using propensity score matching between SILS and MULS. Baseline characteristics, operative outcomes, and postoperative complications were compared. RESULTS: No significant differences in baseline characteristics and pathologic features were found between the two groups. Operation time, estimated blood loss, and postoperative major complication were not significantly different (119.0 min vs 141.6 min, p = 0.275; 200.0 mL min vs 373.3 min, p = 0.222; 0 vs 0, p = 1.000). However, postoperative hospital stay was significantly shorter in SILS (2.73 days vs 7.67 days, p = 0.005). CONCLUSIONS: Solo SILS had comparable postoperative complications and feasibility in the aspect of operation time and hospital stay compared with conventional MULS for a favorable located single HCC.

Prognostic Factors of Patients with Stercoral Perforation of the Colon.

Background/Aims: The incidence of stercoral perforation of the colon (SPC) is expected to rise, given the increased life expectancy and the aging population. On the other hand, the prognostic factors of mortality after surgery for SPC remain unclear. This study examined the prognostic factors of patients with SPC after surgery. Methods: The medical records of 145 patients who underwent surgery for colonic perforation between April 2010 and May 2019 were reviewed retrospectively. In 145 patients, 22 patients who underwent SPC surgery were categorized into the following two groups according to in-hospital survival after surgery: alive (group A, n=15) and dead (group B, n=7). Results: In all enrolled patients, the mean age was 75.7±9.0 years, with a female predominance (female patients, n=19, 86.4%). Sixteen patients (72.7%) had chronic constipation with medications, and five patients (22.7%) were bedridden. The rate of preoperative bedridden status was significantly higher in group B than group A (6.7% vs. 57.1%; p=0.021). Univariate analysis revealed immobility, a sequential organ failure assessment (SOFA) score, and lactate levels of more than 2.0 mmol/L to be factors associated with increased mortality rates in the postoperative period. Multivariate analysis revealed abnormal lactate levels to be the only factor related to mortality (hazard ratio 16.50, 95% CI 1.48-183.07, p=0.022). Conclusions: Preoperative abnormal serum lactate levels may be a risk factor for mortality after surgery in patients with stercoral perforation. Further research will be needed to identify the postoperative prognostic SPC factors.

Low-intensity ultrasound attenuates paw edema formation and decreases vascular permeability induced by carrageenan injection in rats.

BACKGROUND: Therapeutic potential of low-intensity ultrasound (LIUS) has become evident in various musculoskeletal diseases. We have previously shown that LIUS has an inhibitory effect on local edema in various diseases including the arthritis and brain injury. In this study, we examined whether LIUS can attenuate paw edema formation vis-à-vis vascular permeability and inflammation in rats induced by carrageenan. LIUS with a frequency of 1 MHz and the intensities of 50, 100, or 200 mW/cm2 were exposed on rat paws for 10 min immediately after carrageenan injection. RESULTS: Carrageenan injection induced paw edema which was peaked at 6 h and gradually decreased nearly to the initial baseline value after 72 h. LIUS showed a significant reduction of paw edema formation at 2 and 6 h at all intensities tested. The highest reduction was observed at the intensity of 50 mW/cm2. Histological analyses confirmed that LIUS clearly decreased the carrageenan-induced swelling of interstitial space under the paw skin and infiltration of polymorphonuclear leukocytes. Moreover, Evans Blue extravasation analyses exhibited a significant decreases of vascular permeability by LIUS. Finally, immunohistochemical staining showed that expression of pro-inflammatory proteins, namely, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) induced by carrageenan injection was reduced back to the normal level after LIUS stimulation. CONCLUSIONS: These results provide a new supporting evidence for LIUS as a therapeutic alternative for the treatment of edema in inflammatory diseases such as cellulitis.

Solo single incision laparoscopic cholecystectomy using the parallel method; Surgical technique reducing a steep learning curve.

BACKGROUNDS/AIMS: To describe the techniques, short-term outcomes, and learning curve of solo single-incision laparoscopic cholecystectomy (Solo-SILC) using a laparoscopic scope holder. METHODS: A total of 591 patients who underwent Solo-SILC from July 2014 to December 2016 performed by four experienced hepatobiliary surgeons were retrospectively assessed. Solo-SILC was performed using the parallel method using a scope holder. The moving average method was used to investigate the learning curve in terms of operative time. RESULTS: In total, 590 Solo-SILC procedures were performed. Very few procedures were converted to multi-port laparoscopic cholecystectomy. There was one case of bile duct injury. The mean operative time (59.93±25.77 min) was shorter than that in other studies of SILC. Three postoperative complications, delaying bile leakage, occurred in the patients treated by one surgeon. These cases were resolved by ultrasound-guided puncture and drainage. The learning curve for surgeons A, B, and C was overcome after 14, 12, and 12 cases. Surgeon D, who had the most experience with SILC, had no obvious learning curve. CONCLUSIONS: Hepatobiliary surgeons experienced in LC can perform Solo-SILC almost immediately. Solo-SILC using the parallel technique represents a more stable option and is a promising treatment for gallbladder disease.

Purely laparoscopic extended right hemihepatectomy for hepatocellular carcinoma with bile duct tumor thrombus.

BACKGROUND: Laparoscopic liver resection (LLRs) was first introduced in the 1990s and has been performed throughout the world [1,2]. And in recent times, minor LLRs are being done for treatment of hepatocellular carcinoma [1]. Although minor LLRs appear as standardized procedures, major LLRs are still limited to few expert teams [3]. VIDEO: There were severe adhesions in the peritoneal cavity due to previous cholangitis and transarterial chemoembolization (TACE). During hepatic hilar dissection, an enlarged lymph node was detected which was negative for malignancy on the frozen biopsy. Without doing the Pringle's maneuver, superficial parenchymal dissection was performed using energy device while the deep part of the liver was dissected by using a CUSA. Because partial segment IV was involved by tumor, the middle hepatic vein could not be preserved. The dilated right bile duct was identified and transected. During the resection of the duct, tumor thrombus was detected intraluminally. After complete removal of the tumor thrombus, the bile duct was closed with continuous suture. The right hepatic vein was ligated with an Endo-stapler. RESULTS: This operation took about 300 minutes and estimated blood loss was 400 ml. The patient was discharged 10 days after operation without significant postoperative complication. The histopathologic report showed a 4.2 × 2.3 × 2.2cm hepatocellular carcinoma (pT2) with clear resection margin. CONCLUSIONS: This video shows the technical feasibility of laparoscopic major liver resection including extended right hemihepatectomy for hepatocellular carcinoma.

Comparison of pure laparoscopic and open living donor right hepatectomy after a learning curve.

This study aims to compare the early outcomes between pure laparoscopic living donor right hepatectomy (PLDRH) and open living donor right hepatectomy (ODRH) after those learning curve. Our analysis was based on 78 consecutive cases of living liver donor, who underwent right hepatectomy, of which 43 underwent ODRH and 35 PLDRH. The learning curve for each group was analyzed. Donor characteristics were comparable between the two groups. Two donors in the PLDRH required conversion to an open due to bleeding and large graft size (open conversion rate: 6.06%). The following outcomes during the study period were comparable between the two groups: operative time (P = .64); estimated blood loss (EBL; P = .86); intra-operative transfusion (P = .57); hospital stay (P = .41); and postoperative complications (P = .51). The operative time stabilized for the ODRH group after 17 cases and for the PLDRH group after 15 cases. After the learning curve, the EBL was lower for PLDRH than ODRH (P = .04). Pure laparoscopic living donor right hepatectomy can be performed as safely as ODRH and with a lower volume of EBL once the surgeon has attained an appropriate level of learning.

Evaluation of MARK BTM for Quantitative Measurement of Three Tumor Markers: Prostate Specific Antigen, Alpha Fetoprotein, and Carcinoembryonic Antigen.

BACKGROUND: Tumor marker assays have played a crucial role for screening cancers and monitoring cancer patients, as they reflect the status and prognosis of patients. Alpha fetoprotein (AFP), prostate specific antigen (PSA), and carcinoembryonic antigen (CEA) are the most commonly used tumor marker proteins. The MARK BTM immunoassay system is a novel platform based on magnetic nanoparticles and electrochemical immunoassay. METHODS: The analytical performance of MARK BTM immunoassay system for determination of AFP, PSA, and CEA are evaluated. Comparisons of methods are also conducted by comparing the assay results of MARK BTM immunoassay system to that of cobas e 801 system. RESULTS: The MARK BTM immunoassay system provides within-run, between-run, and between-day precisions for the three tumor markers, ranging from 1.13 - 7.46%. Data measured by the MARK BTM immunoassay system show high correlation with that of the cobas e 801 system, with a linear slope ranging from 0.966 to 1.042 and a correlation coefficient of r > 0.996 for the three markers. CONCLUSIONS: These results show that the MARK BTM immunoassay system can be used for the quantitative measurements of AFP, PSA, and CEA in clinical practice.

Current Status of Discarded Grafts in Korean Organ Transplantation.

OBJECTIVES: Despite the severe shortage of available organs, many are discarded after procurement. This study aims to analyze the current status of discarded organs (retrieved, but not transplanted organs) from deceased donors in Korea. METHODS: Deceased donor organ and procurement data were collected from the Korean Network for Organ Sharing and Korea Organ Donation Agency database from 2013 to 2016. RESULTS: Between 2013 and 2016, a total of 6315 deceased donor organ transplants were performed nationwide. A total of 63 organs were discarded. The most commonly discarded organs were kidney (n = 24), followed by islet cell (n = 23), lung (n = 9), liver (n = 6), and pancreas (n = 1). The most common cause for discarding solid organs was poor organ condition (n = 24). Other reasons included aggravation of donor condition, incidental cancer detection of the donor, and the abscence of matching recipient. Islet cells (n = 23) were not used because of inadequate separation and purification. CONCLUSIONS: To reduce unnecessary graft discard in Korea, systems-based improvements in preprocurement organ evaluation and postprocurement preservation are imperative.

Spleen Preservation in Laparoscopic Distal Pancreatectomy for Solid Pseudopapillary Neoplasm is Oncologically Safe.

Purpose: Laparoscopic distal pancreatectomy (LDP) has been widely performed for solid pseudopapillary neoplasm (SPN) involving the body or tail of the pancreas. However, it has not been established whether spleen preservation in LDP is oncologically safe for the treatment of SPN with malignant potential. In this study, we compared the short- and long-term outcomes between patients with SPN who underwent laparoscopic spleen-preserving distal pancreatectomy (LSPDP) vs laparoscopic distal pancreatectomy with splenectomy (LDPS). Methods: We retrospectively reviewed the medical records of 46 patients with SPN who underwent LDP between January 2005 and November 2016. Patients were divided into 2 groups according to spleen preservation: the LSPDP group (n=32) and the LDPS group (n=14). Clinicopathologic characteristics and perioperative outcomes were compared between groups. Results: There were no significant differences in pathologic variables, including tumor size, tumor location, node status, angiolymphatic invasion, or perineural invasion between groups. Median operating time was significantly longer in the LSPDP group vs the LDPS group (243 vs 172 minutes; p=0.006). Estimated intraoperative blood loss was also significantly greater in the LSPDP group (310 vs 167 ml; p=0.063). There were no significant differences in incidence of postoperative complications (≥ Clavien-Dindo class IIIa) or pancreatic fistula between groups. After a median follow-up of 35 months (range, 3~153 months), there was no recurrence or disease-specific mortality in either group. Conclusion: The results show that LSPDP is an oncologically safe procedure for SPN involving the body or tail of the pancreas.

Fatigue and weakness hinder patient social reintegration after liver transplantation.

BACKGROUND/AIMS: With improvements in the survival of liver transplantation (LT) recipients, the focus is shifting to patient quality of life (QOL), and employment is an important factor in aiding the social reintegration of LT patients. This study aims to evaluate the current employment status of liver graft recipients and various factors that may hinder reemployment. METHODS: Fifty patients above age 18 who underwent either living or deceased donor LT at a single center from March 2009 to July 2016 were interviewed during their visit to the outpatient clinic. The internally developed questionnaire consisted of 10 items. The Karnofsky Performance Scale and EQ-5D were used to evaluate patient function and QOL. RESULTS: A total of 25 (50%) patients returned to work after transplantation (the working group), and 21 (84%) patients in the working group returned to work within the first year after transplantation. In the non-working group (n=25), 17 (68%) answered that their health was the reason for unemployment. Fatigue and weakness were the most frequent symptoms. CONCLUSION: The data shows that as many as 50% of total patients returned to work after receiving LT. Fatigue and weakness were the most common complaints of the unemployed group, and resolving the causes of these symptoms may help to increase the employment rate.

Laparoscopic distal pancreatectomy for neuroendocrine tumors of the pancreas.

The incidence of incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (PNETs) is increasing because of the widespread use of radiologic imaging studies. Due to their mostly small size, PNETs in the body and tail of the pancreas are suited for laparoscopic surgery. This video described our technique of laparoscopic distal pancreatectomy with and without preservation of spleen and splenic vessels for PNET. The decision on preservation of spleen and splenic vessels was made according to the relative location of tumors to the splenic vessels.

A blunt dissection technique using the LigaSure vessel-sealing device improves perioperative outcomes and postoperative splenic-vessel patency after laparoscopic spleen- and splenic-vessel-preserving distal pancreatectomy.

BACKGROUND: We have recently performed a blunt dissection technique using LigaSure technology for laparoscopic spleen- and splenic-vessel-preserving distal pancreatectomy to reduce the risk of bleeding during the dissection of the splenic vessels. The aim of this study was to compare the utility of the blunt dissection technique and a conventional dissection technique during laparoscopic spleen- and splenic-vessel-preserving distal pancreatectomy. METHODS: Fifty-five patients who underwent laparoscopic spleen- and splenic-vessel-preserving distal pancreatectomy performed by a single surgeon between March 2003 and December 2015 were enrolled in this retrospective single-center study. The patients were divided into the LigaSure group (n = 23) and non-LigaSure group (n = 26). Perioperative clinical outcomes and the postoperative patency of the preserved splenic vessels in the two groups were compared. RESULTS: The patient and tumor characteristics did not differ significantly between the two groups. The incidence of postoperative complications was similar in the two groups. However, the mean operative time (145 vs. 231.1 min, P = 0.001), intraoperative blood loss (95.6 vs. 360 ml, P = 0.001), and postoperative hospital stay (6.4 vs. 9.8 days, P = 0.001) were significantly lower in the LigaSure group than in the non-LigaSure group, respectively. The splenic artery patency rate was similar in both groups, but the splenic vein patency was significantly better in the LigaSure group than in the non-LigaSure group (total occlusion rate: 4.5 vs. 30.8%, respectively, P = 0.017). CONCLUSION: The results of this study suggest that the blunt dissection technique using a LigaSure reduces the operating time and intraoperative blood loss during laparoscopic spleen- and splenic-vessel-preserving distal pancreatectomy and increases the patency of the preserved splenic vessels.

Transplantation of human bone marrow-derived clonal mesenchymal stem cells reduces fibrotic scar formation in a rat spinal cord injury model.

This study aimed to evaluate the therapeutic effect on tissue repair and scar formation of human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) homogeneously isolated by using a subfractionation culturing method, in comparison with the non-clonal MSCs (hMSCs), in a rat spinal cord injury (SCI) model. The SCI was made using a vascular clip at the T9 level. Cells were transplanted into the lesion site 3 days after injury. A functional test was performed over 4 weeks employing a BBB score. Rats were killed for histological analysis at 3 days, 1 week and 4 weeks after injury. The transplantation of hMSCs and hcMSCs significantly reduced lesion size and the fluid-filled cavity at 4 weeks in comparison with the control group injected with phosphate buffered saline (PBS) (p < 0.01). Transplantation of hcMSCs showed more axons reserved than that of hMSCs in the lesion epicentre filled with non-neuronal tissues. In addition, hMSCs and hcMSCs clearly reduced the inflammatory reaction and intraparenchymal hemorrhaging, compared with the PBS group. Interestingly, hcMSCs largely decreased Col IV expression, one of the markers of fibrotic scars. hcMSCs yielded therapeutic effects more than equal to those of hMSCs on the SCI. Both hMSCs and hcMSCs created an increase in axon regeneration and reduced scar formation around the SCI lesion. Copyright © 2017 John Wiley & Sons, Ltd.

The effect of dry needling and treadmill running on inducing pathological changes in rat Achilles tendon.

Achilles tendinopathy is a common degenerative condition without a definitive treatment. An adequate chronic animal model of Achilles tendinopathy has not yet been developed. The purpose of this study was to evaluate the individual and combined effects of dry needling and treadmill running on the Achilles tendon of rats. Percutaneous dry needling, designed to physically replicate microrupture of collagen fibers in overloaded tendons, was performed on the right Achilles tendon of 80 Sprague-Dawley rats. The rats were randomly divided into two groups: a treadmill group, which included rats that underwent daily uphill treadmill running (n = 40), and a cage group, which included rats that could move freely within their cages (n = 40). At the end of weeks 1 and 4, 20 rats from each group were sacrificed, and bilateral Achilles tendons were collected. The harvested tendons were subjected to mechanical testing and histological analysis. Dry needling induced histological and mechanical changes in the Achilles tendons at week 1, and the changes persisted at week 4. The needled Achilles tendons of the treadmill group tended to show more severe histological and mechanical changes than those of the cage group, although these differences were not statistically significant. Dry needling combined with free cage activity or treadmill running produced tendinopathy-like changes in rat Achilles tendons up to 4 weeks after injury. Dry needling is an easy procedure with a short induction period and a high success rate, suggesting it may have relevance in the design of an Achilles tendinopathy model.

Low intensity ultrasound inhibits brain oedema formation in rats: potential action on AQP4 membrane localization.

AIMS: Brain oedema is a major contributing factor to the morbidity and mortality of a variety of brain disorders. Although there has been considerable progress in our understanding of pathophysiological and molecular mechanisms associated with brain oedema so far, more effective treatment is required and is still awaited. Here we intended to study the effects of low intensity ultrasound (LIUS) on brain oedema. METHODS: We prepared the rat hippocampal slice in vitro and acute water intoxication in vivo models of brain oedema. We applied LIUS stimulation in these models and studied the molecular mechanisms of LIUS action on brain oedema. RESULTS: We found that LIUS stimulation markedly inhibited the oedema formation in both of these models. LIUS stimulation significantly reduced brain water content and intracranial pressure resulting in increased survival of the rats. Here, we showed that the AQP4 localization was increased in the astrocytic foot processes in the oedematous hippocampal slices, while it was significantly reduced in the LIUS-stimulated hippocampal slices. In the in vivo model too, AQP4 expression was markedly increased in the microvessels of the cerebral cortex and hippocampus after water intoxication but was reduced in the LIUS-stimulated rats. CONCLUSIONS: These data show that LIUS has an inhibitory effect on cytotoxic brain oedema and suggest its therapeutic potential to treat brain oedema. We propose that LIUS reduces the AQP4 localization around the astrocytic foot processes thereby decreasing water permeability into the brain tissue.

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on glial scar formation after spinal cord injury in rats.

OBJECT: This study investigated the effects of granulocyte colony-stimulating factor (G-CSF) on glial scar formation after spinal cord injury (SCI) in rats and compared the therapeutic effects between G-CSF and granulocytemacrophage colony-stimulating factor (GM-CSF) to evaluate G-CSF as a potential substitute for GM-CSF in clinical application. METHODS: Rats were randomly assigned to 1 of 4 groups: a sham-operated group (Group 1), an SCI group without treatment (Group 2), an SCI group treated with G-CSF (Group 3), and an SCI group treated with GM-CSF (Group 4). G-CSF and GM-CSF were administered via intraperitoneal injection immediately after SCI. The effects of G-CSF and GM-CSF on functional recovery, glial scar formation, and axonal regeneration were evaluated and compared. RESULTS: The rats in Groups 3 and 4 showed better functional recovery and more decreased cavity sizes than those in Group 2 (p < 0.05). Both G-CSF and GM-CSF suppressed intensive expression of glial fibrillary acidic protein around the cavity at 4 weeks and reduced the expression of chondroitin sulfate proteoglycans (p < 0.05). Also, early administration of G-CSF and GM-CSF protected axon fibers from destructive injury and facilitated axonal regeneration. There were no significant differences in comparisons of functional recovery, glial scar formation, and axonal regeneration between G-CSF and GM-CSF. CONCLUSIONS: G-CSF suppressed glial scar formation after SCI in rats, possibly by restricting the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans, which might facilitate functional recovery from SCI. GM-CSF and G-CSF had similar effects on glial scar formation and functional recovery after SCI, suggesting that G-CSF can potentially be substituted for GM-CSF in the treatment of SCI.