Victim profiles and revealed issues of type 1 Emergency Medical Team in the first minutes of a mega earthquake in Turkey.

BACKGROUND: On February 6, 2023, a series of mega-earthquakes (MEs) struck the southern parts of Turkey and northern Syria. In the first 16 days after the Turkey MEs (TMEs), the Tokushukai Medical Assistant Team (TMAT) backed by its infrastructure visited Turkey to support a local hospital. With the goal of helping local communities and working with local supporters and authorities, Turkey is on a mission to positively impact people's lives. METHODS: Data collected covered the TMAT support period in February 2023. All patients admitted to a hospital were registered through the Minimum Data Set (MDS) of the Emergency Medical Team (EMT) Coordination Cell (EMTCC). RESULTS: A total of 561 patients were hospitalized during the 16-day mission. A review of the MDS data showed a de-crease in the number of inpatients. The number of diseases directly related to the disaster was confirmed to be due to a gradual decrease in TME aftershock. However, the number of patients with nondisaster-related disease remained stable. CONCLUSION: The experience of EMT in the initial relief of MEs that struck Turkey and Syria on February 6, 2023 showed that a mobile type 1 EMT in the early stage while rebuilding the infrastructure is essential. From the analysis of patient profiles, it is clear that knowledge and experience of skin diseases is needed in the first minutes of MEs. In addi-tion, it has become clear that to ensure the quality of MDS for further analysis and to improve the efficiency and effec-tiveness of EMS, it is essential to have recorders in the EMS. These MDS recorders, called descriptors, must be isolated from the treating medical staff to eliminate subjectivity and ensure data accuracy.

Short-term outcomes of OTSC for anastomotic leakage after laparoscopic colorectal surgery.

INTRODUCTION: There are several reports on the use of the over-the-scope clip (OTSC) for gastrointestinal bleeding/fistula and endoscopic iatrogenic perforation. However, there are almost no reports on OTSC use for anastomotic leakage (AL) after colorectal cancer surgery. The purpose of this study was to evaluate the outcome of AL closure using the OTSC. MATERIAL AND METHODS: Five patients who had undergone AL after laparoscopic surgery for colorectal cancer from April 2017 to April 2019 were evaluated. RESULTS: The average distance from the anal verge of the anastomosis site was 12 (5-18) cm. The average diameter of the dehiscent part was 10.9 (9.3-14.4) mm. The average number of OTSC days after the occurrence of AL was 11 (5-22). On the contrast examination immediately after OTSC, all cases were completely closed, but in the later contrast examination, only one case remained completely closed. The average incompletely closed diameter was 3.6 (2.9-5.1) mm, and the diameter of the dehiscent part was reduced in all cases. Only one patient ultimately underwent colostomy; the rest were cured with OTSC alone. CONCLUSION: AL site closure using the OTSC after colorectal cancer surgery is a useful minimally invasive treatment when combined with appropriate drain management.

Neoadjuvant chemoradiotherapy for locally advanced gastric cancer with bulky lymph node metastasis: Five case reports.

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) has not been accepted as a general therapy for gastric cancer because of its localized effect and toxicity for radiosensitive organs. However, if radiation therapy could compensate for the limited or inadequate treatment choices available for elderly patients and/or those at high risk, the available therapeutic options for advanced gastric cancer might increase. From this perspective, we present our experiences of five patients with advanced gastric cancer in whom we used NACRT therapy with interesting results. CASE SUMMARY: We admitted five patients with clinical Stage III gastric cancer and bulky lymph node metastasis or adjacent organ invasion at the time of diagnosis. A total of 50 Gy of preoperative intensity modulated radiation therapy was delivered to the patients in doses of 2.0 Gy/d, together with a regimen of concomitant chemotherapy comprising two courses of oral tegafur/gimeracil/oteracil (S-1; 65 mg/m2 per day) for three consecutive weeks followed by two weeks of rest, starting at the same time as radiotherapy. All patients underwent no residual tumor resection and a pathological complete response of the primary tumors was achieved in two patients. The incidence of hematological toxicity was low, although the digestive toxicities of anorexia and diarrhea developed in three of the five patients, necessitating termination of radiation therapy at 30 Gy and S-1 at three weeks. However, even 30 Gy of irradiation and half the dose of S-1 resulted in sufficient downstaging, indicating that even a reduced amount of NACRT could confer considerable effects. CONCLUSION: Slightly reduced NACRT might be useful and safe for patients with locally advanced gastric cancer.

Photoinduced Pyramidal Inversion Behavior of Phosphanes Involved with Aggregation-Induced Emission Behavior.

Invited for the cover of this issue is Kenta Kokado and co-workers at Hokkaido University. The cover picture describes the interesting pyramidal inversion behavior of phosphanes in the excited state, like entering "the Mirror World", which we found in this research. Read the full text of the article at 10.1002/chem.202000264.

Evaluation of laparoscopic surgery for small bowel obstruction and factors related to outcomes.

INTRODUCTION: In recent years, laparoscopic surgery (LS) has been performed for small bowel obstruction (SBO). However, the indications and short-term and long-term outcomes of LS for SBO have not yet been established. AIM: To evaluate the usefulness of LS for SBO compared to open surgery (OS), as well as to identify risk factors for poor outcomes after LS. MATERIAL AND METHODS: A total of 105 patients who underwent surgery for SBO were divided into OS (n = 64) and LS (n = 41) groups, and propensity score-matched analysis was used to compare the short-term and long-term outcomes of the groups. Risk factors for conversion to OS, postoperative complications, and intraoperative bowel injury in LS were also identified. RESULTS: The incidences of surgical site infection and postoperative ileus were significantly lower in the LS group. The incidence of recurrent bowel did not differ significantly between the two groups. Prior bowel obstruction was a risk factor for conversion of LS to OS (odds ratio (OR) = 24.79, p = 0.0025). Bowel diameter was a risk factor for postoperative complications (OR = 1.50, 95% CI: 1.01-2.22) and for bowel injury (OR = 1.33, 95% CI: 1.05-1.67). CONCLUSIONS: LS for SBO had better postoperative short-term outcomes than OS. The outcomes of LS for SBO were significantly affected by prior bowel obstruction and bowel diameter.

Photoinduced Pyramidal Inversion Behavior of Phosphanes Involved with Aggregation-Induced Emission Behavior.

Aggregation-induced emission (AIE) is a fascinating phenomenon because of the applications of luminescent materials in the aggregated state, which exploit the large structural changes of the molecules in the excited state. Recently, it was reported that triphenylphosphane derivatives show AIE behavior in which they undergo potentially large structural changes in the excited state. Inspired by this report, photoinduced pyramidal inversion behavior of phosphanes was investigated. In photochemical experiments, the prepared P-stereogenic phosphanes exhibited photoracemization in dilute solution, and a negative correlation was observed between the photoracemization and the AIE phenomenon. Theoretical computations revealed that the inversion barrier in the excited state was much smaller than that in the ground state. This is the first report on the photoinduced pyramidal inversion behavior of phosphanes, which will provide new and unexplored applications.

Short- and Long-term Outcomes of 2-Step Stapled Intracorporeal Versus Extracorporeal Anastomosis in Laparoscopic Colectomy for Colon Cancer.

BACKGROUND/AIM: Intracorporeal anastomosis (IA) in laparoscopic colectomy for colon cancer is technically difficult, and there is a lack of consensus on the risk of bacterial contamination and cancer cell dissemination. In this study, short- and long-term outcomes of IA were examined. PATIENTS AND METHODS: Short and long-term outcomes of those who underwent IA (n=44) or extracorporeal anastomosis (EA) (n=61) were compared. RESULTS: IA was better than EA for blood loss, incision length, and first stool. Maximum temperature and C-reactive protein on postoperative day 1 were higher for the IA group. The rate of positive cultures from intraoperative lavage was higher for IA. The rate of positive cultures improved to an equivalent level by replacing mechanical pretreatment with chemical pretreatment. IA and EA were equivalent for the results of ascites cytology from lavage. CONCLUSION: With the use of appropriate preoperative treatment, IA takes advantage of the minimally invasive nature of laparoscopic surgery.

Low psoas muscle index is a poor prognostic factor for lower gastrointestinal perforation: a single-center retrospective cohort study.

BACKGROUND: Various body composition indices have been reported as prognostic factors for different cancers. However, whether body composition affects prognosis after lower gastrointestinal tract perforation requiring emergency surgery and multidisciplinary treatment has not been clarified. This study examined whether body composition evaluations that can be measured easily and quickly from computed tomography (CT) are useful for predicting prognosis. METHODS: Subjects comprised 64 patients diagnosed with perforation at final diagnosis after emergency surgery for a preoperative diagnosis of lower gastrointestinal tract perforation and penetration. They were divided into a survival group and a non-survival (in-hospital mortality) group and compared. Body composition indices (psoas muscle index (PMI); psoas muscle attenuation (PMA); subcutaneous adipose tissue index (SATI); visceral adipose tissue index (VATI); visceral-to-subcutaneous fat area ratio (VSR)) were measured from preoperative CT. Cross-sectional psoas muscle area at the level of the 3rd lumbar vertebra was quantified. Optimal cut-off values were calculated using receiver operating characteristic curve analysis. Poor prognostic factors were investigated from multivariate logistic regression analyses that included patient factors, perioperative factors, intraoperative factors, and body composition indices as explanatory variables. RESULTS: The cause of perforation was malignant disease in 12 cases (18.7%), and benign disease in 52 cases (81.2%). The most common cause was diverticulum of the large intestine. Emergency surgery for the 64 patients led to survival in 52 patients and death in 12 patients. On multivariate logistic regression analysis, independent predictors of poor prognosis were Sequential Organ Failure Assessment score (odds ratio 1.908; 95% confidence interval (CI) 1.235-3.681; P = 0.0020) and PMI (odds ratio 13.478; 95%CI 1.342-332.690; P = 0.0252). The cut-off PMI was 4.75 cm2/m2 for males and 2.89 cm2/m2 for females. Among survivors, duration of hospitalization was significantly longer in the low PMI group (29 days) than in the high PMI group (22 days, p = 0.0257). CONCLUSIONS: PMI is easily determined from CT and allows rapid evaluation of prognosis following lower gastrointestinal perforation.

Functional Evaluation for Various Methods of Gastrectomy and Reconstruction for Gastric Cancer.

OBJECTIVE: This study of 45 patients aimed to retrospectively examine whether the relationships among the postoperative to preoperative body weight ratio (BWR), meal intake as a good indicator of quality of l ife (QOL), and absorptive kinetics from the small intestine could be expressed by the acetaminophen (AAP) concentration. METHODS: The postoperative/preoperative BWR and meal intake ratio (MIR) were evaluated in 30 patients who underwent open distal gastrectomy for advanced gastric cancer (ODG group) and 15 patients who underwent laparoscopic proximal gastrectomy for early gastric cancer (LPG group). In addition, all patients underwent functional evaluation using the AAP method. Correlation coefficients of the BWR and MIR with the plasma AAP concentration after meal intake were evaluated. RESULTS: There was a negative correlation between the AAP concentration at 15 min and the BWR in all patients (r = -0.438, P = 0.00259, n = 45) and a weak negative correlation between the AAP concentration at 15 min and the MIR (r = -0.309, P = 0.0368, n = 45). CONCLUSIONS: There were some relationships between slow intestinal absorption in the early postprandial phase and the maintenance of postoperative body weight and meal intake. Namely, operative methods that maintained preoperative slow intestinal absorption were thought to be better for maintaining postoperative QOL.

Recurrent Cervical Cancer with Intestinal Perforation That Was Related to Bevacizumab after Long-term NSAIDs Administration and Was Treated with Laparoscopy-assisted Anastomosis.

Bevacizumab is an effective drug for recurrent/advanced cervical cancer. A 59-year-old patient diagnosed with FIGO stage I B2 squamous cell carcinoma of the cervix at our hospital was treated with concurrent chemoradiotherapy as initial treatment. The outcome was judged as close to CR. Local recurrence in the irradiation field and paraaortic lymph node metastasis were noted 2 months after completion of this treatment. Chemotherapy of bevacizumab combined with paclitaxel plus carboplatin (TC) was initiated for recurrent cervical cancer. At 17 days after the 4th cycle, abdominal pain suddenly developed, and a close examination detected free air on abdominal CT, based on which intestinal perforation was diagnosed. Laparoscopic surgery performed to investigate the intraabdominal cavity showed that the small intestine was perforated at 2 sites. These were treated with laparoscopy-assisted partial resection of the small intestine and functional end-to-end anastomosis. Drug therapy for the recurrent cervical cancer was considered, but the primary disease rapidly aggravated and the patient died of the primary disease 11 months after completion of the initial treatment.

Colon cancer arising from colonic diverticulum: A case report.

BACKGROUND: Colonic diverticulosis is a common disease, and the coexistence of colonic diverticulosis and colorectal cancer is often seen clinically. It is very rare that colon cancer arises from the mucosa of a colonic diverticulum. When colon cancer arises in a diverticulum and then tends to develop outside the wall, without developing within the lumen, the differential diagnosis from complicating lesions due to colonic diverticulitis is difficult. CASE SUMMARY: A 76-year-old man was admitted to a nearby clinic with a chief complaint of discomfort and urinary frequency. Since a vesicosigmoidal fistula was seen on abdominal computed tomography, he was referred to our hospital. Laparoscopic sigmoidectomy was performed because the various diagnostic findings were diagnosed as a vesicosigmoidal fistula with diverticulitis of the sigmoid colon. However, on histopathological examination, it was diagnosed as a vesicosigmoidal fistula due to colon cancer arising in the diverticulum. Laparoscopic partial resection of the bladder was performed because local recurrence was observed in the bladder wall one and a half years after surgery. It is currently one year after reoperation, but there has been no recurrence or metastasis. CONCLUSION: Colon cancer arising in a diverticulum of the colon should be considered when diverticulitis with complications is observed.

Functional evaluations comparing the double-tract method and the jejunal interposition method following laparoscopic proximal gastrectomy for gastric cancer: an investigation including laparoscopic total gastrectomy.

PURPOSE: Functional outcomes were prospectively compared between two types of reconstruction [double tract (L-DT; n = 15) and jejunal interposition (L-JIP; n = 15)] following laparoscopic half-proximal gastrectomy (LPG), including laparoscopic total gastrectomy (L-TG; n = 30) as a control group, at 1 year after surgery. METHODS: Clinical investigations were performed in each patient, and functional evaluations, involving the swallowing of an alimentary liquid containing acetaminophen (AAP), followed by measurements of the concentrations of AAP and hormones in the sitting (n = 5) and in the supine positions (n = 5), were carried out in each group. RESULTS: The post-/preoperative body weight ratios were significantly higher in the L-DT and L-JIP groups than in the L-TG group. The AAP levels were significantly lower in the LPG group than in the LTG group. The AAP, insulin, and gastrin levels in the L-JIP group were markedly increased in the sitting position compared with the supine position, while those in the L-DT and L-TG groups were stable in both positions. CONCLUSIONS: L-JIP and L-DT are procedures that maintain gradual intestinal absorption and help improve the quality of life. Intestinal absorption and hormonal secretion were relatively unaffected by the posture of the meal intake after L-DT, so L-DT might be the procedure providing the most stable results.

Oncostatin M-induced blood-brain barrier impairment is due to prolonged activation of STAT3 signaling in vitro.

Oncostatin M (OSM) is a member of the interleukin (IL)-6 family cytokines. We previously demonstrated that OSM induces blood-brain barrier (BBB) impairment. However, functional characterization of IL-6 family cytokines in BBB regulation and the cytokine-related intracellular signaling pathway remain unclear. In this study, we demonstrate that among IL-6 family cytokines, including IL-6 and leukemia inhibitory factor (LIF), OSM is the most potent molecule for inducing BBB dysfunction via prolonged activation of signal transducer and activator of transcription (STAT) 3 following Janus-activated kinase (JAK) activation. OSM but not IL-6 and LIF (100 ng/mL for 24 hours) markedly produced increased sodium fluorescein permeability and decreased transendothelial electrical resistance in rat brain endothelial cell (RBEC) monolayers. This OSM-induced BBB dysfunction was accompanied by decreased levels of claudin-5 expression in RBECs, which were ameliorated by JAK inhibitor. We examined the time-course of STAT3 phosphorylation in RBECs treated with OSM, IL-6, and LIF. OSM upregulated STAT3 phosphorylation levels during a 24 hours period with a peak at 10 minutes. While IL-6 and LIF transiently increased phosphorylated STAT3 at 10 minutes after addition, this phosphorylation decreased during the period from 1 to 24 hours after addition. These findings suggest that OSM-induced sustained increases in STAT3 phosphorylation levels largely contribute to BBB impairment. Thus, elevated OSM levels and activation of brain endothelial JAK/STAT3 signaling pathway under pathological conditions should be considered as a possible hallmark for induction and development of BBB impairment.

TNF-α-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IκB-NFκB and JAK-STAT3 pathways.

Interleukin (IL)-6 is an important mediator of neurovascular dysfunction, neurodegeneration and/or neuroinflammation. We previously reported that brain pericytes released higher levels of IL-6 than did glial cells (astrocytes and microglia) in response to tumor necrosis factor (TNF)-α. Moreover, pericytes stimulated with TNF-α enhanced activation of BV-2 microglia. In this study, we investigated the mechanisms of TNF-α mediated induction of IL-6 release from brain pericytes and astrocytes and whether pericyte-derived IL-6 would facilitate activation of BV-2 microglia. Using rat brain pericyte and astrocyte primary cultures and pharmacological inhibitors, we found that, TNF-α induced the highest levels of IL-6 release from pericytes by activating the inhibitor kappa B (IκB)-nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and Janus family of tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT)3 pathways. STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation.

Two Cases of Laparoscopic Diagnosis and Treatment of Intersigmoid Hernia.

We present two cases of intestinal obstruction due to intersigmoid hernia that were diagnosed and treated laparoscopically. The first case was a 42-year-old woman with no surgical history. She was treated conservatively with the insertion of an ileus tube. Although the intestinal obstruction improved temporarily, since it subsequently worsened, laparoscopic surgery was performed, which revealed incarceration of the ileum in the intersigmoid fossa. Although there were no signs of necrosis after intestinal release, partial resection of the small bowel was performed before the hernial orifice was closed due to the evidence of serous damage. The second case was a 53-year-old man with no surgical history. An ileus tube was inserted for intestinal decompression, following which laparoscopic surgery was performed. Operative findings revealed incarceration of the ileum in the intersigmoid fossa, and, since there were no signs of necrosis after intestinal release, the hernial orifice was closed without performing intestinal resection. This condition is a good indication for laparoscopic surgery, given that intestinal necrosis is frequently absent and the operation can usually be completed simply by release of the incarcerated intestine and closure of the hernia orifice. Intersigmoid hernia should be suspected in cases of intestinal obstruction with no surgical history.

Contribution of thrombin-reactive brain pericytes to blood-brain barrier dysfunction in an in vivo mouse model of obesity-associated diabetes and an in vitro rat model.

Diabetic complications are characterized by the dysfunction of pericytes located around microvascular endothelial cells. The blood-brain barrier (BBB) exhibits hyperpermeability with progression of diabetes. Therefore, brain pericytes at the BBB may be involved in diabetic complications of the central nervous system (CNS). We hypothesized that brain pericytes respond to increased brain thrombin levels in diabetes, leading to BBB dysfunction and diabetic CNS complications. Mice were fed a high-fat diet (HFD) for 2 or 8 weeks to induce obesity. Transport of i.v.-administered sodium fluorescein and 125I-thrombin across the BBB were measured. We evaluated brain endothelial permeability and expression of tight junction proteins in the presence of thrombin-treated brain pericytes using a BBB model of co-cultured rat brain endothelial cells and pericytes. Mice fed a HFD for 8 weeks showed both increased weight gain and impaired glucose tolerance. In parallel, the brain influx rate of sodium fluorescein was significantly greater than that in mice fed a normal diet. HFD feeding inhibited the decline in brain thrombin levels occurring during 6 weeks of feeding. In the HFD fed mice, plasma thrombin levels were significantly increased, by up to 22%. 125I-thrombin was transported across the BBB in normal mice after i.v. injection, with uptake further enhanced by co-injection of unlabeled thrombin. Thrombin-treated brain pericytes increased brain endothelial permeability and caused decreased expression of zona occludens-1 (ZO-1) and occludin and morphological disorganization of ZO-1. Thrombin also increased mRNA expression of interleukin-1ß and 6 and tumor necrosis factor-α in brain pericytes. Thrombin can be transported from circulating blood through the BBB, maintaining constant levels in the brain, where it can stimulate pericytes to induce BBB dysfunction. Thus, the brain pericyte-thrombin interaction may play a key role in causing BBB dysfunction in obesity-associated diabetes and represent a therapeutic target for its CNS complications.

Role of thrombin-PAR1-PKCθ/δ axis in brain pericytes in thrombin-induced MMP-9 production and blood-brain barrier dysfunction in vitro.

Thrombin, an essential component in the coagulation cascade, participates in the pathogenesis of brain diseases, such as ischemic stroke, intracerebral hemorrhage, Alzheimer's disease and Parkinson's disease through blood-brain barrier (BBB) dysfunction. It is thought that the thrombin-matrix metalloproteinase (MMP)-9 axis is an important process in the pathogenesis of neurovascular disease, such as BBB dysfunction. We recently reported that brain pericytes are the most MMP-9-releasing cells in response to thrombin stimulation among the BBB-constituting cells. This thrombin-induced MMP-9 release is partially due to protease-activated receptor (PAR1), one of the specific thrombin receptors. Then, we evaluated the intracellular signaling pathways involved in MMP-9 release and the contribution of thrombin-reactive brain pericytes to BBB dysfunction. PKC activator evoked MMP-9 release from brain pericytes. The thrombin-induced MMP-9 release was inhibited by U0126, LY294002, Go6976, and Go6983. However, Go6976 decreased phosphorylation levels of PKCθ and Akt, and Go6983 decreased phosphorylation levels of PKCδ and extracellular signal-regulated kinase (ERK). Additionally, treatment of pericytes with thrombin or PAR1-activating peptide stimulated PKCδ/θ signaling. These substances impaired brain endothelial barrier function in the presence of brain pericytes. Brain pericytes function through two independent downstream signaling pathways via PAR1 activation to release MMP-9 in response to thrombin - the PKCθ-Akt pathway and the PKCδ-ERK1/2 pathway. These pathways participate in PAR1-mediated MMP-9 release from pericytes, which leads to BBB dysfunction. Brain pericytes and their specific signaling pathways could provide novel therapeutic targets for thrombin-induced neurovascular diseases.

Liquefaction-induced emission enhancement of tetraphenylethene derivatives.

A typical AIE dye, TPE, was liquefied by attaching long and branched alkyl chains. The obtained liquid dye showed intense emission compared to the solid dye or TPE. The linkage between TPE and the alkyl chain led to significant difference in their photoluminescent and thermal properties.

A Case of Idiopathic Mesenteric Phlebosclerosis with Progressive Intestinal Necrosis.

The patient was a 39-year-old woman who was referred to our department from her previous doctor with a 2-day history of right abdominal pain. Abdominal computed tomography showed wall thickening associated with calcification in the ascending colon. Contrast enhancement in the same portion of the intestinal wall was rather poor. Fluid accumulation was also seen around the intestine, so emergency surgery was performed under a provisional diagnosis of intestinal necrosis. Intestinal necrosis due to idiopathic mesenteric phlebosclerosis was diagnosed from postoperative histopathological tests. Idiopathic mesenteric phlebosclerosis displays a chronic course and in most cases conservative treatment is indicated. Bowel obstruction is common among patients who require surgical treatment, but rare cases such as the present one are also seen in which intestinal necrosis occurs. In recent years, an association with herbal medicine has been indicated as one potential cause of this disease, and this entity should be kept in mind when patients with acute abdomen and a history of taking herbal medicines are encountered.

Brain pericytes are the most thrombin-sensitive matrix metalloproteinase-9-releasing cell type constituting the blood-brain barrier in vitro.

In the acute phase of intracerebral hemorrhage (ICH), hemorrhagic transformation and brain edema are associated with blood-brain barrier (BBB) disruption. Elevated levels of thrombin, a coagulation factor, contribute to the development of brain edema during ICH through matrix metalloproteinase (MMP)-9 production. Thrombin directly induces a variety of cellular responses through its specific receptors known as protease-activated receptors (PARs). However, it remains unclear which cell types constituting the BBB mainly produce MMP-9 in response to thrombin. Here, we compared the MMP-9 release induced by thrombin using primary cultures of rat brain microvascular endothelial cells, astrocytes, and pericytes. Brain pericytes exhibited the highest levels of MMP-9 release due to thrombin stimulation among the BBB cells. The pattern of PAR mRNA expression in pericytes was characterized by high expression of PAR1 and moderate expression of PAR4. Heat-inactivated thrombin failed to stimulate pericytes to release MMP-9. A selective PAR1 inhibitor SCH79797 blocked the thrombin-induced MMP-9 release from pericytes. These findings suggest that both PAR1 and PAR4 mediate thrombin-induced MMP-9 release from pericytes. The present study raises the possibility that brain pericytes could play a pivotal role as a highly thrombin-sensitive and MMP-9-producing cell type at the BBB in brain damage including ICH.