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Pathological specimens were collected from 14 unruptured and 13 ruptured aneurysms at the time of clipping and studied in order to assess the underlying mechanism of rupture by investigating degeneration of the aneurysmal wall and possible involvement of apoptosis. Immunohistochemistry with anti-actin antibody showed few smooth muscle cells in the ruptured aneurysms and replacement of the muscularis layer by a fibro-hyalin tissue. However, at least one layer of smooth muscle cells was clearly observed in the unruptured aneurysms. Thus, smooth muscle cells in the wall of the ruptured aneurysms were much more degenerated than those in the wall of unruptured aneurysms. In addition, unruptured aneurysms with an angiographically smooth wall showed well-layered positive staining for anti-smooth muscle actin antibody while those with irregular shapes rarely reacted. We found, for the first time, evidence of DNA fragmentation in the aneurysmal wall. Apoptotic bodies were detected by means of a terminal transferase (TdT)-mediated dUTP biotin nick end labelling technique (TUNEL) and an anti-single-stranded DNA antibody in 54% (7/13) of the ruptured aneurysms. In contrast, apoptotic bodies were found in only 7% (1/14) of the unruptured cases. These results suggest that apoptotic cell death might be involved in the rupture of aneurysms. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: A new method for prevention of cerebrospinal fluid leakage was studied. OBJECTIVE: To prevent cerebrospinal fluid leakage, we developed a polytetrafluoroethylene fascia patch inlay method. BACKGROUND: One of the major risks of the anterior approach for intra-dural spinal cord lesions is the cerebrospinal fluid leakage. METHODS: A small hemangioblastoma located on the ventral side of the cervical cord was resected with an anterior approach. The dural closure was performed using this polytetrafluoroethylene fascia patch inlay method. RESULTS: The patient had a satisfactory clinical course with no cerebrospinal fluid leakage. CONCLUSION: This polytetrafluoroethylene fascia patch inlay method is very effective. This method may provide both prevention of CSF leakage and future spinal cord adhesion to the dura. [ABSTRACT FROM AUTHOR]

Understanding the mass transfer characteristics of matrix diffusion and sorption is important in the safety assessment of geological disposal of high-level radioactive waste in crystalline rock (granite) by contributing to radionuclide retardation through mass transfer within the rock body. We present a comparative discussion of the effective diffusion coefficient ( De ), porosity, and petrological data for rock samples collected from the Toki Granite in central Japan, to evaluate the role of micropores within minerals in retardation by matrix diffusion and sorption in granitic rocks. De was derived from the through-diffusion experiments using uranine, barium, strontium, and chloride ions as tracers. Petrological data consist of the fracture frequency, the extent of hydrothermal alteration in the minerals, the micropore volume in the minerals, and the three-dimensional modal mineralogy (mineral assemblage and ratio) for the target rock samples. The relationship between the De , porosity, and petrological data has the following implications: 1) Micropores in minerals related to the alteration act as 'storage pores' that contribute to retardation due to matrix diffusion and sorption; 2) Once the uranine, cations (Ba 2+ and Rb + ), and anion (Cl - ) penetrate the micropores in the minerals through matrix diffusion, the cations are sorbed on the micropore surfaces, whereas the uranine and conservative chloride anion is trapped at the end of the micropore network, resulting in retardation; 3) Regions with a high fracture frequency are associated with not only active advection-dispersion through fractures, but also retardation due to matrix diffusion and sorption; 4) The grain-boundary pores between colorless minerals act as 'transport pores' owing to matrix diffusion, and the retardation within grain-boundary pores is less than that within micropores in minerals., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Takashi Yuguchi reports financial support was provided by 10.13039/501100001691Japan Society for the Promotion of Science. Eiji Sasao reports financial support was provided by 10.13039/501100001691Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic process to identify the physical, psychological, and social functions of patients with frailty. The Clinical Frailty Scale (CFS) might aid in effectively identifying older patients with heart failure (HF) and frailty who would then reap maximum benefits from the CGA. Methods and Results: A single-centre prospective cohort study that enrolled consecutive hospitalised patients (age ≥75 years) with HF was conducted. The Barthel index (BI), Mini Mental State Examination (MMSE), the Charlson comorbidity index (CCI), and the COntrolling NUTritional (CONUT) for CGA was used. Among 190 enrolled patients (mean age, 85.4 years; 47.9% male), all-cause mortality (primary endpoint) occurred in 45 patients and HF-related rehospitalization (secondary endpoint) in 59 patients within 1 year. The cumulative incidence of all-cause mortality was significantly higher in the high CFS group (low 6.3%, high 30.5%, P<0.001). However, the cumulative incidence of HF-related rehospitalization was not significantly different (low 26.3%, high 32.0%, P=0.304). The multivariable analysis revealed that the CFS group was independently associated with the risk of all-cause mortality. CFS showed a strong correlation with the BI and moderate correlation with the MMSE. Conclusions: The CFS was associated with all-cause mortality within 1 year and was correlated with frailty domains of CGA., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Extensive control efforts have significantly reduced malaria cases and deaths over the past two decades, but in recent years, coupled with the COVID-19 pandemic, success has stalled. The WHO has urged the implementation of a number of interventions, including vaccines. The modestly effective RTS,S/AS01 pre-erythrocytic vaccine has been recommended by the WHO for use in sub-Saharan Africa against Plasmodium falciparum in children residing in moderate to high malaria transmission regions. A second pre-erythrocytic vaccine, R21/Matrix-M, was also recommended by the WHO on 3 October 2023. However, the paucity and limitations of pre-erythrocytic vaccines highlight the need for asexual blood-stage malaria vaccines that prevent disease caused by blood-stage parasites. Few asexual blood-stage vaccine candidates have reached phase 2 clinical development, and the challenges in terms of their efficacy include antigen polymorphisms and low immunogenicity in humans. This review summarizes the history and progress of asexual blood-stage malaria vaccine development, highlighting the need for novel candidate vaccine antigens/molecules.

Purpose: This study aims to investigate the factors influencing post-treatment visual acuity (VA) in patients with central retinal vein occlusion (CRVO) with macular edema (ME)., Methods: The subjects of this study were patients who visited our clinic from May 2013 to July 2019 and who could be followed up with for at least 12 months. Cases with hemi CRVO were excluded from this study. Factors considered in the evaluation of visual prognosis at the 12 months included initial best-corrected VA, central subfoveal thickness, CRVO subtype (nonischemic, ischemic, or converted from nonischemic to ischemic), time taken for the first treatment, number of anti-vascular endothelial growth factor agent injections, structural changes in the inner and outer retinal layers, and the presence of macular ischemia in a multiple regression analysis., Results: There were 41 patients with 41 eyes, 27 males and 14 females. The mean age of the patients was 70.5 ± 12.2 (mean ± standard deviation) years. The mean VA was 0.544 ± 0.576, 0.456 ± 0.568, and 0.586 ± 0.665 at the initial visit, 12 months later, and time of last observation, respectively. There were no significant differences in VAs observed between the baseline, month 12, and final visit. Multiple regression analysis revealed that the external limiting membrane score at month 12 ( p = 0.030), the VA at initial visit ( p < 0.001), and the presence of severe macular ischemia ( p < 0.001) were the key factors associated with VA at month 12. Moreover, severe macular ischemia was identified as the only factor affecting decimal VA less than 20/200 at the last observation ( p = 0.0092)., Conclusions: Severe macular ischemia is strongly linked to a poor visual prognosis in patients with ME associated with CRVO.

Purpose: To report a case of refractory macular hole (MH) in pseudophakic eye treated with autologous posterior capsule flaps transplantation., Methods: Case report., Results: A 48-year-old man visited our hospital with visual loss in the right eye because of unclosed MH. The patient had undergone two previous surgeries in another hospital, that is, the first included a cataract surgery, vitrectomy, and internal limiting membrane peeling with sulfur hexafluoride (SF 6 ) gas tamponade, and the second included an ineffective autologous internal limiting membrane flap technique and massaging the edges of the MH with a soft-tipped flute needle followed by the same gas, but the MH remained open. In our hospital, posterior capsule flaps were acquired from the same eye, inserted into the MH, and the same gas tamponade was performed, which was about four months after the disease onset (3 months after the prior second surgery). The patient kept face-down position for a week after the surgery and the MH was closed, which remained for over 12 months. The visual acuity improved from 20/250 to 20/60, and the retinal sensitivities around the MH gradually improved., Conclusion: An autologous posterior capsule flaps transplantation was effective in the management of refractory MH to not only close the MH but also improve the visual outcomes.

Purpose: To assess the rotational stability of a new toric intraocular lens (IOL), TECNIS toric II (toric II), which is a modified version of the TECNIS toric IOL (toric I) with frosted haptics (Johnson & Johnson)., Methods: A total of 101 eyes of 101 patients who had been treated with phacoemulsification and toric IOL implantation were included. Before and 1 day, 1 week, and 1 month after surgery, uncorrected (UDVA) and corrected (CDVA) distance visual acuity were measured. Preoperative corneal astigmatism and postoperative manifest refractive astigmatism at 1 day and 1 month were analyzed. At 1 day and 1 month postoperatively, the amount of IOL axis misalignment from the intended orientation, tilt, and decentration were measured using anterior segment optical coherence tomography., Results: Fifty-one eyes received the toric I IOL and 50 eyes received the toric II IOL. Toric I IOLs showed a significantly larger amount of axis misalignment than toric II IOLs at both 1 day (9.6 ± 7.6° vs 5.4 ± 4.8°, P = .003) and 1 month (9.1 ± 7.8° vs. 4.7 ± 4.2°, P = .003) postoperatively.The proportion of eyes with misalignment greater than 10° was significantly larger with toric I than toric II IOLs ( P < .001). There were no significant differences between IOLs in the amount of residual astigmatism, UDVA, CDVA, and amount of tilt and decentration at 1 day and 1 month postoperatively., Conclusions: The TECNIS toric II IOL with frosted haptics has significantly improved rotational stability compared to its previous model. [ J Refract Surg . 2022;38(10):648-653.] .

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cancer-related complication that induces pulmonary hypertension (PH). PTTM can be caused by recurrent cancer, with 12 years being the longest reported interval from primary cancer to the development of PTTM. We herein report a 74-year-old woman who presented with dyspnea due to PH. The postmortem diagnosis was PTTM caused by recurrent gastric cancer 26 years after total gastrectomy. An autopsy revealed PTTM-specific histological characteristics. Our findings indicate that PTTM should be considered as a diagnosis for patients with a history of cancer who develop PH, even several decades after treatment.

This study aims to test the hypothesis that the effect of excimer laser coronary angioplasty (ELCA) not only vaporizes thrombi and their underlying coronary plaque, it also changes their quality. We performed a series of cross-sectional analyses in 52 lesions in 51 patients before and after ELCA with integrated backscatter-intravascular ultrasound (IB-IVUS). The constituent parts of the plaque can be assessed by IB-IVUS (i.e., calcified, fibrous, lipid) according to integrated backscatter values. Minimum lumen diameter, lumen volume and vessel volume expanded after ELCA, while plaque volume did not significantly decrease. There was also a decrease of 'lipid' component (35.4-30.3%, P < 0.001) and an increase of IB-IVUS-derived 'fibrous' part (34.5-38.3%, P < 0.001). These results may help in understanding plaque change after ELCA. Excimer laser coronary angioplasty seems to contribute to the modification of coronary plaque composition in addition to debulking it., (© 2021. The Author(s).)

Biotites occur with varying degrees of alteration within a granite. This study analyzes the relationships among alteration indicators, areal microvoid fractions in chloritized biotite, and macroscopic fracture frequencies in the Toki granite, central Japan, to establish the genesis and development processes of fractures in granite. Appropriate characterizations for the frequency distribution of macroscopic fractures in granite can assist in understanding potential hydrogeological applications, which contributes to safety evaluations for geological disposal and storage. Borehole 06MI03, drilled to a depth of 191 m, was used to obtain samples for the analysis. In total, 24 samples that depicted variations in the macroscopic fracture frequency were selected. Petrographic alteration indicators using biotite chloritization as innovative methods are proposed to evaluate the extent of hydrothermal alteration and fracture frequency within granites. The alteration indicators are defined as the ratio between the alteration product area and the original mineral area. Furthermore, the volume of microscopic fractures and micropores in the mineral was quantitatively characterized by the areal fraction of microvoids in minerals through image analysis. Samples with high macroscopic fracture frequencies correspond to a high number of areal microvoid fractions and large alteration indicators. Microvoids, which are the source of macroscopic fractures, occurred at temperatures between 350 and 780°C and can be evaluated by intrinsic factors, such as alteration indicators. Subsequent faulting and unloading (extrinsic factors) developed microvoids into macroscopic fractures. Intrinsic factors are used to evaluate the source of macroscopic fractures, and therefore contribute to the characterization of present and future distributions of macroscopic fracture frequencies., Competing Interests: The authors have declared that no competing interests exist.

Erythrocyte recognition and invasion is critical for the intra-erythrocytic development of Plasmodium spp. parasites. The multistep invasion process involves specific interactions between parasite ligands and erythrocyte receptors. Erythrocyte-binding-like (EBL) proteins, type I integral transmembrane proteins released from the merozoite micronemes, are known to play an important role in the initiation and formation of tight junctions between the apical end of the merozoite and the erythrocyte surface. In Plasmodium yoelii EBL (PyEBL), a single amino acid substitution in the putative Duffy binding domain dramatically changes parasite growth rate and virulence. This suggests that PyEBL is important for modulating the virulence of P. yoelii parasites. Based on these observations, we sought to elucidate the receptor of PyEBL that mediates its role as an invasion ligand. Using the eukaryotic wheat germ cell-free system, we systematically developed and screened a library of mouse erythrocyte proteins against native PyEBL using AlphaScreen technology. We report that PyEBL specifically interacts with basigin, an erythrocyte surface protein. We further confirmed that the N-terminal cysteine-rich Duffy binding-like region (EBL region 2), is responsible for the interaction, and that the binding is not affected by the C351Y mutation, which was previously shown to modulate virulence of P. yoelii . The identification of basigin as the putative PyEBL receptor offers new insights into the role of this molecule and provides an important base for in-depth studies towards developing novel interventions against malaria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuguchi, Kanoi, Nagaoka, Miura, Ito, Takeda, Tsuboi, Takashima and Otsuki.)

This study presents the K-Ar geochronology for hydrothermal K-feldspar in plagioclase alteration, including methodology and application to the Toki granite, in central Japan. Borehole samples from the Toki granite were collected and mechanically and chemically processed to separate plagioclase from the rock and remove bulk impurities. The sample fraction of cleaned plagioclase powder was further processed to a smaller size fraction, allowing separation of the altered K-feldspar from the plagioclase host. The resulting K-feldspar represented the hydrothermal alteration product and was characterized crystallographically as microcline, and its K-Ar ages were measured. The results of the K-Ar dating and petrographic characterization indicated that in this setting, plagioclase alteration occurred through a combination of solid-state replacement and dissolution-precipitation processes. The K-feldspathization age enables constraint of the temporal conditions of the solid-state replacement process to 62.2 ± 1.4 Ma. The time-temperature ( t-T ) path of the sampling site is an effective tool for determining both the timing and thermal conditions of the hydrothermal microcline formation in plagioclase alteration. The combination of the t-T path and the microcline K-Ar age provides formation temperatures of about 307-325 °C. The timing and thermal conditions of solid-state replacement (62.2 ± 1.4 Ma and 325-307 °C) indicate an older age and a higher temperature than those of dissolution-precipitation (59.2 ± 1.4 Ma and 305-290 °C: Yuguchi et al., 2019A). The plagioclase alteration consists of serial processes from solid-state replacement to dissolution-precipitation. Addition of the thermal conditions and timing into petrography have implications for the sequential phenomenal variation in granite., (© 2021 The Author(s).)

We evaluated the rotational stability of a new toric intraocular lens (IOL), HOYA XY-1 toric IOL that is an improved version of HOYA 355 toric IOL, with longer overall length (13.0 mm vs. 12.5 mm), shortened unfolding time, and texture processing of the surface of haptics. Data from 193 eyes of 165 patients (76.4 ± 8.3 years old) with preoperative corneal astigmatism exceeding 0.75 diopters who had undergone phacoemulsification and toric IOL implantation were collected and analyzed. Corneal astigmatism, refractive astigmatism, and uncorrected (UDVA) and corrected distance visual acuity (CDVA) were evaluated before and 1 day, 1 week, and 1 month after surgery. The degree of IOL decentration, IOL tilt, and toric axis misalignment was assessed at 1 day and 1 month postoperatively. Fifty eyes received AcrySof toric IOL, 51 eyes TECNIS toric IOL, 46 eyes HOYA 355 toric IOL, and 46 eyes HOYA XY-1 toric IOL. The amount of axis misalignment from the intended axis was significantly different among IOLs (p = 0.004, one-way ANOVA), and HOYA XY-1 showed significantly less amount of axis misalignment than TECNIS (p = 0.020, Tukey's multiple comparison) and HOYA 355 (p = 0.010). The proportion of eyes that showed axis misalignment <10° at 1 month postoperatively was significantly higher with HOYA XY-1 toric IOL than with other toric IOLs (χ2 test, p = 0.020). HOYA XY-1 toric IOL, the modified version of HOYA 355 toric IOL, showed excellent rotational stability in comparison with other models of toric IOLs., Competing Interests: Tetsuro Oshika has received research grants and speaker honorarium from Alcon, HOYA, and Johnson & Johnson Vision. Other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The analysis of the distribution of microfractures and micropores is important to accurately characterise mass transfer within a rock body. In this paper, a new 'simultaneous polarization-fluorescence microscopy' method is presented, which can be used to analyse the distribution of microscopic voids, including microfractures and micropores, in granitic rock. In this method, thin sections prepared with fluorescent dye are analysed under a polarizing microscope equipped with a fluorescent reflected light source. Using both the transmitted and the fluorescent light sources, both the distribution of microfractures and micropores, and petrographic characteristics (mineral occurrences) can be determined efficiently and simultaneously. The distribution of microfractures and micropores observed in images of granites obtained using simultaneous polarization-fluorescence microscopy is consistent with the distribution observed in backscattered electron images. The low magnification characterisation of the distribution of microscopic voids also provides targeting for subsequent studies including scanning electron microscopy under high magnification, chemical analysis, and image processing., (© 2020 The Author(s).)

Simultaneous determination of zircon U-Pb age and titanium concentration for a single analysis spot gives both the crystallization age and temperature. In laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis, it is challenging to quantitatively analyse a low level of titanium concentration. Two approaches were employed using a quadrupole mass spectrometer equipped with a collision/reaction cell (CRC). In the first approach, the MS/MS mass-shift mode with oxygen reaction gas provided reliable and consistent measurement of titanium as 48 Ti 16 O + . In the second approach, the titanium concentration was determined quantitatively from the signal intensity of 49 Ti in the non-gas mode (without the inflow of collision/reaction gas into the CRC). The methods were applied to zircon samples of the Kurobegawa granite (KRG), the Okueyama granite (OKG), the Toki granite (TKG), and the Tono plutonic complex (TCP). The biotite K-Ar geochronology were employed for rock samples of the KRG, OKG, and TPC (N = 3) of which the zircon crystals were analysed. The obtained titanium concentrations of the zircon crystals can lead to the crystallization temperatures through Ti-in-zircon geothermometer., Competing Interests: This research was carried out under a contract with the Ministry of Economy, Trade and Industry (METI) as part of its R&D supporting program titled “Establishment of Advanced Technology for Evaluating the Long-term Geosphere Stability (2019 Fy)” A part of this work was financially supported by a JSPS KAKENHI for Young Scientists [grant number 16H06138] to TY. The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Author(s).)

Malaria symptoms and pathology are initiated by invasion of host erythrocytes by Plasmodium merozoites in a complex process that involves interactions between parasite and host erythrocyte proteins. Erythrocyte invasion presents attractive targets for malaria vaccine and drug development. Recently it was observed that antibodies against PfMSA180 (PF3D7&#95;1014100) are associated with protection from symptomatic malaria, suggesting that this protein is a target of naturally acquired protective antibodies. Here we characterize PfMSA180, a ~170 kDa merozoite surface antigen that is potentially involved in erythrocyte invasion. PfMSA180 synthesized by the wheat germ cell-free system was used to raise antibodies in rabbits. Growth inhibition assays revealed that parasite invasion is inhibited by antibodies to the PfMSA180 C-terminal region, which contains an erythrocyte-binding domain. Surface plasmon resonance analysis showed that PfMSA180 specifically interacts with human erythrocyte integrin associated protein (CD47), suggesting that PfMSA180 plays a role during merozoite invasion of erythrocytes. Polymorphism analysis revealed that pfmsa180 is highly conserved among field isolates. We show that naturally acquired PfMSA180-specific antibodies responses are associated with protective immunity in a malaria-exposed Thai population. In sum, the data presented here supports further evaluation of the conserved erythrocyte-binding C-terminal region of PfMSA180 as an asexual blood-stage malaria vaccine candidate.

To elucidate the pituitary function of Japanese patients after aneurysmal subarachnoid hemorrhage (aSAH) and implicative factors related to growth hormone deficiency (GHD) after aSAH. We evaluated basal pituitary hormone levels among 59 consecutive aSAH patients with a modified Rankin Scale (mRS) ⩽4 at 3months after aSAH onset. Patients with low insulin-like growth factor 1 (IGF-1) SD score (SDS) or who seemed to develop pituitary dysfunction underwent provocative endocrine testing during a period of 3-36months after SAH onset. The relationship between IGF-1 SDS and clinical factors of the patients such as severity of SAH, aneurysm location, and treatment modalities, were assessed. Six patients (10.2%) demonstrated their IGF-1 SDS less than -2. Multiple logistic regression analyses revealed that patients who underwent surgical clipping had a significantly lower IGF-1 SDS (<-1SD) than patients who underwent endovascular embolization with an odds ratio of 5.83 (p=0.032). Thirty-three patients took provocative tests and five (15.6%) patients were identified as having GHD. The mean IGF-1 SDS of these five GHD patients was 0.08 SD. The aneurysms in all GHD patients were located in internal carotid artery (ICA) or anterior cerebral artery (ACA). To the best of our knowledge, this is the first report describing the prevalence of GHD in Japanese patients after aSAH, and it was not as high as that of previous European studies. We recommend that screening pituitary dysfunction for aSAH survivors with their aneurysms located in ICA or ACA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: We evaluated the clinical outcomes of malignant middle cerebral artery (MCA) infarction (MMI) and determined an infarcted brain volume (BV) threshold value for accurate MMI prediction in elderly patients., Methods: We analyzed 69 consecutive patients (mean, 75.6 ± 11.7) with internal carotid artery or MCA infarction within 48 hours from onset. Diffusion-weighted high-intensity volume (DHV) and BV were measured in all patients. The percentage of DHV within BV (DHV/BV ratio) was calculated to standardize the DHV difference for each individual BV. Patients were stratified based upon their MMI status and age, compared with the following: (1) MMI versus non-MMI groups and (2) age ≥75 years group versus age <75 years group, based on DHV values, DHV/BV ratio, Glasgow Coma Scale (GCS) scores on admission, and modified Rankin Scale (mRS) scores at 3 months after onset., Results: The MMI group (n = 14) showed significantly larger DHV values (P < .001), larger DHV/BV ratios (P < .001), lower GCS scores on admission (P < .01), and higher mRS scores at 3 months (P < .001) than the non-MMI group. The DHV threshold value predicting MMI was 102 cm(3) (sensitivity 85%, specificity 91%, P < .01) and DHV/BV threshold ratio was 7.8% (sensitivity 86%, specificity 87%, P < .01). Both the age ≥75 years group and the age <75 years group with MMI showed equally poor outcomes (mRS 5.7 ± .7 versus 5.3 ± 1.3)., Conclusions: DHV and DHV/BV can provide reliable information for MMI prediction in elderly patients., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Spinal epidural arachnoid cyst (EAC) is a rare, usually asymptomatic condition of unknown origin, which typically involves the lower thoracic spine. We report a case of posttraumatic symptomatic EAC with lumbar disc herniation. A 22-year-old man experienced back pain and sciatica after a traffic accident. Neurological examination revealed a right L5 radiculopathy. Magnetic resonance imaging demonstrated a cystic lesion at the L3 to L5 level and an L4-5 disc herniation; computed tomography myelography showed that the right L5 root was sandwiched between the cyst and the herniation. A dural defect was identified during surgery. The cyst was excised completely and the defect was repaired. A herniation was excised beside the dural sac. Histology showed that the cyst wall consisted of collagen and meningothelial cells. Postoperatively the symptoms resolved. Lumbar spinal EACs are rare; such cysts may arise from a congenital dural crack and grow gradually. The 6 cases of symptomatic lumbar EAC reported in the literature were not associated with disc herniation or trauma. In this case, the comorbid disc herniation was involved in symptom progression. Although many EACs are asymptomatic, comorbid spinal disorders such as disc herniation or trauma can result in symptom progression.

A 54-year-old female patient had a 6-year history of backache and left sciatica. Five years earlier, she had undergone surgery in another hospital for left L4-5 disc herniation. Computed tomography revealed the ossified wall that enclosed the left L5 nerve root. There were also osteophytic changes in the left L5-S zygapophyseal joint. These osteophytes developed rostrally, along the left L5 nerve root, throug h the intervertebral foramina. We performed decompression surgery for the left L5 nerve root, and surgery resulted in symptomatic relief. We experienced a rare clinical presentation of osteophytic formation, with a specific configuration in relation to the nerve root. Surgeons should be aware of entrapment of the lumbar spinal nerve by advanced osteophytic changes occurring in the zygapophyseal joint after lumbar surgery.

In order to maintain the adequate tumor margin in partial hepatectomy, we developed a new guide technique using a fine transhepatic tube. For instance, in a case of anterior segment tumor, a fine needle following a tube was inserted into the liver beside the anterior portal pedicle at hepatic hilus, and was put forward to the confluence of right and middle hepatic veins. After the needle was pulled out, both edges of the tube were tugged to the Rex Cantlie line. A separation was then started from the liver surface down to the transhepatic tube. Subsequently, the tube was pulled to the right side, and another separation was done. Adequate disease-free surgical margins were kept in thirteen out of 15 various types of partial hepatectomies. There were no complications including injury to the vessels and stabbing of the tumor. This technique facilitates cutting of the deep parenchyma.

Object: Microscopic bilateral decompression through a unilateral laminotomy (MBDUL) is a minimally invasive technique used to treat lumbar canal stenosis (LCS). In the present study, MBDUL was performed to treat LCS in eight patients undergoing hemodialysis., Methods: Surgical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scale (highest possible score 29). The JOA scale was administered preoperatively, at 1 month and 3 months postoperatively, and at the final follow-up examination. One patient refused to undergo the postoperative assessment after the 1-month examination; the mean follow-up duration of the remaining seven patients was 24 months (range 18-31 months). The mean age at the time of surgery was 62 years (range 48-76 years), and the mean duration of hemodialysis therapy was 21.4 years (range 3-28 years). All patients could walk within 2 days of surgery. The mean angle of the straight leg-raising (SLR) test was 53.8 degrees preoperatively, and this increased to 69.4 degrees postoperatively. Six patients felt enhancement of sciatica or leg pain when performing the SLR test preoperatively, a finding that was absent postoperatively at least until the final follow-up examination. The mean preoperative JOA score was 11.6 (range 4-22), and the score markedly improved to 19.8 (range 15-23) at 1 month and 20.6 (range 16-25) at 3 months. The mean JOA score decreased to 17.1 (range 12-25) at the final follow-up examination, but this decrease was attributed to other physical disorders., Conclusions: The authors conclude that MBDUL is a safe and effective surgical treatment for patients undergoing hemodialysis who are suffering from LCS.

Apolipoproteins play an important role in cell repair and have been found to increase shortly after traumatic brain injury (TBI). In addition, apolipoproteins reduce amyloid-beta (Abeta) accumulation in models of Alzheimer's disease. Considering that TBI induces progressive neurodegeneration including Abeta accumulation, we explored potential long-term changes in the gene and protein expression of apolipoproteins E and J (ApoE and J) over 6 months after injury. Anesthetized male Sprague-Dawley rats were subjected to parasagittal fluid-percussion brain injury and their brains were evaluated at 2, 4, 7, 14 days, and 1 and 6 months after TBI. In situ hybridization, Western blot, and immunohistochemical analysis demonstrated that although there was a prolonged upregulation in both the gene expression and protein concentration of ApoE and J after injury, these responses were uncoupled. Upregulation of ApoE and J mRNA expression lasted from 4 days to 1 month after injury. In contrast, a biphasic increase in protein concentration and number of immunoreactive cells for ApoE and ApoJ was observed, initially peaking at 2 days (i.e., before increased mRNA expression), returning to baseline by 2 weeks and then gradually increasing through 6 months postinjury. In addition, ApoE and J were found to colocalize with Abeta accumulation in neurons and astrocytes at 1-6 months after injury. Collectively, these data suggest that ApoE and J play a role in the acute sequelae of brain trauma and reemerge long after the initial insult, potentially to modulate progressive neurodegenerative changes., ((c) 2005 Wiley-Liss, Inc.)

The synthetic pyrazolopyrimidine, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) is a novel, potent, and selective inhibitor of Src family tyrosine kinases. Vascular permeability appears to be mediated by vascular endothelial growth factor (VEGF), which requires the activation of downstream Src family kinases to exert its function. This study investigates the effects of PP1 on vascular permeability and inflammatory response in a rat spinal cord compression model. Ten minutes after compression, PP1 (PP1 group) or the vehicle only (control group) was administered. On days 1, 3, and 7 after compression, the spinal cords were removed and examined histopathologically to determine the expression of VEGF and the extent of edema and inflammation. The dryweight method was used to measure the water content of the spinal cords. The mRNA levels of tumor necrosis factor a (TNFalpha) and interleukin 1beta (IL-1beta), which is related to inflammatory responses, were measured with a real-time polymerase chain reaction (RT-PCR) system 6 h after compression. Although VEGF expression was similar in both groups, the extent of contusional lesion in the PP1 group was reduced by approximately 35% on day 3. Moreover, the water content on days 1, 3, and 7 was significantly reduced and macrophage infiltration on days 3 and 7 was dramatically reduced in the PP1 group. TNF and IL-1beta mRNA expression in the PP1 group were also significantly reduced. These results indicate that PP1 reduces secondary damage after spinal cord injury.

Apolipoprotein E (ApoE) is a major apolipoprotein in the central nervous system (CNS) that plays an important role in Alzheimer's disease. It may also be involved in other CNS disorders including ischemic injury. We investigated the changes of ApoE protein and mRNA expression in the brain with middle cerebral artery occlusion (MCAO) to clarify its origin after focal ischemia in rats. Increased ApoE immunoreactivity was recognized in astrocytes 3-14 days after MCAO in the affected side of cortex, and in neurons 4-14 days after MCAO in the same area. ApoE immunoreactivity was also detected in macrophages in the ischemic core 3-14 days after MCAO. In contrast, ApoE mRNA was expressed in astrocytes and macrophages, but not in neurons. These results suggested that neuronal ApoE was not synthesized in neurons, but derived from astrocytes.

We describe the advantages and clarify the technical key points of a microendoscopic, minimally invasive technique to the posterior surgical approach for cervical degenerative disease. The authors studied the microendoscopic posterior approach using the METRx system in both cadaver models and in clinical cases. This new technique needs only a small surgical route thus reducing damage to the paraspinous muscles. Moreover, this technique provides a clear view of the operating points, because of the oblique view angle of the endoscope. This technique is feasible for not only radiculopathy but also myelopathy caused by segmental canal stenosis. Posterior cervical decompression with this system is technically feasible and should be beneficial for reducing post-operative morbidity and spine deformity. This report deals with cases of cervical radiculopathy and segmental canal stenosis operated on with this system as well as the key points of this surgical procedure.

The central noradrenergic system is widely distributed throughout the brain and is closely related to spontaneous motility and level of consciousness. The study presented here evaluated the morphological as well as neurochemical effects of diffuse brain injury on the central noradrenergic system in rat. Adult male Sprague-Dawley rats were subjected to impact-acceleration brain injury produced with a weight-drop device. Morphological changes in locus coeruleus (LC) neurons were examined by using immunohistochemistry for dopamine-beta-hydroxylase, and norepinephrine (NE) turnover in the cerebral cortex was measured by high performance liquid chromatography with electrochemical detection. The size of LC neurons increased by 11% 24 h after injury but had decreased by 27% seven days after injury. Axons of noradrenergic neurons were swollen 24 h and 48 h after injury but the swelling had dwindled in seven days. NE turnover was significantly reduced seven days after injury and remained at a low level until eight weeks after injury. These results suggest that focal impairment of axonal transport due to diffuse brain injury causes cellular changes in LC and that the neurochemical effect of injury on the central noradrenargic system lasts over an extended period of time. Chronic suppression of NE turnover may explain the sustained behavioral and psychological abnormalities observed in a clinical situation.

Following spinal cord injury vascular permeability increases around the area of injury, which possibly leads to secondary tissue damage. Vascular endothelial growth factor (VEGF) and Src which exists downstream of VEGF may contribute to edema formation. We here report that the Src family kinase inhibitor PPI could reduce edema and the inflammatory response after spinal cord injury. In this study we have examined the effect of PPI on motor function after mild spinal cord compression injury. We utilized a mild spinal cord compression model in rats. PPI or vehicle only was administered intraperitoneally after cord compression. The motor function of the hind limbs after injury was categorized into 7 grades. At 1, 3, 7 and 14 days after injury, the spinal cord was removed and the extent of edema formation and inflammation were examined using immunohistochemistry with an anti-IgG and anti-ED-1 antibody. The immunohistochemical analysis revealed that the area of edema formation and inflammation was remarkably reduced in animals with PPI. The muscle function was flaccid in both groups immediately after injury. However, at 3 and 8 days after injury, a significant improvement was observed in the PPI group. These results suggest that PPI is a strong candidate for drug treatment of spinal cord injury.

In clinically hyperthermia and irradiation therapy for malignant neoplasms are known that they have antiproliferative activity and cell death (including apoptosis) inducing activity. However not only mechanisms of cell death induction but treatment effects of them still have been unclear. In this time we showed that cell cycles from G0/G1 phase to S-G2/M phase were delayed by hyperthermia and G2/M phase accumulation were caused immediately by irradiation. And we also demonstrated that the combination treatments of hyperthermia and irradiation induced synergistic antiproliferative effects and strong effects of cell death to human esophageal carcinoma cell lines. Although treatments of hyperthermia and irradiation were mild individually, combination treatment of hyperthermia and irradiation were useful for esophageal carcinoma treatment.

Purpose: To investigate the factors contributing to contraction of the anterior capsule opening (ACO) after cataract surgery in normal eyes., Setting: Department of Ophthalmology, University of Tokyo, School of Medicine, Tokyo, and Kaiya Eye Clinic, Hamamatsu, Japan., Methods: This study included 141 eyes of 141 patients scheduled to have cataract surgery. The area of the ACO was determined by diaphanoscopy using the EAS-1000 anterior eye segment analysis system 1 day and 9 months postoperatively, after which the percentage reduction in the ACO area was calculated. Aqueous flare intensity was measured with a laser flare-cell meter 1 week and 9 months after surgery. Multiple regression analysis was performed to determine which factors were correlated with the percentage reduction in the ACO area. Variables tested included patient age, axial length, the ACO area on the first postoperative day, and flare values 1 week and 9 months after surgery., Results: Patient age (r = 0.193, P =.029) and flare intensity 9 months after surgery (r = 0.255, P =.007) were significantly correlated with the percentage reduction in the ACO area (R(2) = 0.133). The axial length, ACO area 1 day postoperatively, and flare value at 1 week were not correlated with ACO contraction., Conclusion: Contraction of the ACO after cataract surgery is related to instability of the blood-aqueous barrier.

Purpose: To prospectively evaluate the usefulness of a subconjunctival steroid injection given at the completion of cataract surgery in patients with diabetes mellitus., Setting: University of Tokyo School of Medicine, Tokyo, Kaiya Eye Clinic, Hamamatsu, and Jyosai Hospital, Tokyo, Japan., Methods: One hundred four eyes of 104 diabetic patients having routine small incision cataract surgery were randomized into 2 groups. One group received a subconjunctival injection of dexamethasone and the other group did not. Aqueous flare intensity was measured with the laser flare meter preoperatively and 1, 2, 5, 7, and 14 days postoperatively. Another 19 diabetic patients having routine cataract surgery were randomized to receive a subconjunctival steroid injection or not; blood glucose concentration was measured 4 times a day for 3 days postoperatively., Results: There was no significant difference between the 2 groups in aqueous flare values at any postoperative time. The subconjunctival steroid injection induced a transient but significant increase in blood glucose on the day of surgery., Conclusion: A subconjunctival steroid injection given at the completion of cataract surgery in diabetic patients had no beneficial effects.

Purpose: To assess the contraction of continuous curvilinear capsulorhexis after cataract surgery in eyes with past pars plana vitrectomy., Methods: In a prospective study, 16 eyes of 16 patients underwent phacoemulsification and implantation of a foldable acrylic intraocular lens after pars plana vitrectomy. Eyes after intensive or repeated vitrectomy were not included. Twenty eyes of 19 patients served as age-matched controls. Aqueous flare intensity was measured using the laser flare-cell meter 1 year after surgery. The area of anterior capsular opening (ACO) was determined by diaphanoscopy using the anterior eye segment analysis system EAS-1000 at 1 day and 1 year postoperatively., Results: There was no significant difference in the mean ACO area between the vitrectomy and control groups both at 1 day and 1 year postoperatively. Aqueous flare intensity 1 year after surgery was slightly higher in the vitrectomy group, but the difference was not statistically significant., Conclusion: Eyes after simple vitrectomy are not at a higher risk of ACO contraction following cataract surgery.

Aim: To investigate change in the area of anterior capsular opening (ACO) after cataract surgery and its relation to the degree of postoperative anterior inflammation in patients with diabetes mellitus (DM)., Methods: 31 eyes of 31 patients with DM and 30 eyes of 30 normal controls scheduled to undergo cataract surgery were examined prospectively. The area of ACO was measured with an anterior eye segment analysis system (EAS-1000) on the day following surgery and 3, 6, and 12 months after surgery. Comparative analyses were made on the area of ACO relative to the presence of DM and diabetic retinopathy (DR). The percentage reduction of area of ACO was calculated from values 1 day and 12 months after surgery, and multiple regression analysis was performed on the presence of DM, patient age, ACO area on the first postoperative day, and aqueous flare intensity 1 day and 12 months after surgery., Results: The area was significantly smaller in the DM group at 3 (p=0.015, Student's t test), 6 (p=0.011), and 12 (p=0.010) months postoperatively. Patients having DR showed significantly smaller ACO area than the non-DR group 3 (p=0.039), 6 (p=0.033), and 12 (p=0.028) months after surgery. Multiple regression analysis revealed that presence of DM (p=0.003) and aqueous flare intensity 12 months after surgery (p=0.039) significantly correlated with the percentage reduction of area of ACO. Age, ACO area at 1 day postoperatively, and aqueous flare intensity immediately after surgery were not relevant to ACO contraction., Conclusions: Anterior capsular contraction after cataract surgery was greater in eyes of DM patients, especially in those with DR and increased permeability of the blood-aqueous barrier.

delta 12-PGJ2, one of the cyclopentenone prostaglandins and the ultimate metabolite of prostaglandin D2, has been reported to have potent antiproliferative activity on various tumor cells in vitro and in vivo. In this study, the combined effect of delta 12-PGJ2 and hyperthermia on six established cell lines of human esophageal carcinoma (SGF series) was analyzed by an in vitro assay, and the degree of apoptosis induced by this combination was examined to clarify the mechanism of supra-additive effects. In five SGF cell lines, except SGF-7 cells, combination therapy with delta 12-PGJ2 and hyperthermia showed synergistic antiproliferative effects. The supra-additive combined effect of delta 12-PGJ2 and hyperthermia on esophageal cancer cells is attributed to the synergistic induction of apoptosis. delta 12-PGJ2 induced G1 accumulation and apoptosis was induced by delta 12-PGJ2 from G1 phase. Hyperthermia induced G1 accumulation and apoptosis was induced by hyperthermia during all cell phases. Both augmented G1 arrest followed by G1 phase-selective induction of apoptosis and increased apoptotic induction without cell-cycle specificity are responsible for the synergism of combined treatment with delta 12-PGJ2 and hyperthermia.

Tissue plasminogen activator (tPA) has been used to treat acute thrombotic lesions. Roles other than the activation of fibrinolytic pathways have been suggested for tPA in the mature brain. We used the in situ hybridization technique to investigate the changes in tPA mRNA expression within the brain after cortical ablation. We found that expression of tPA mRNA started to increase diffusely in the cortex ipsilateral to the injury 6 h after ablation. This increase had become prominent 24 h after ablation. On d 5, the expression of tPA mRNA had returned to that of the control animals except for the area near the injury. We also found that administration of MK-801 before injury suppressed the increase of tPA mRNA in the ipsilateral cortex. These results suggest that the increase in tPA mRNA is likely to be mediated via activation of NMDA receptors.

We investigated the effect of BDNF mini-pellet on the GAP-43 mRNA expression and functional status of facial nerve in a rat model of facial nerve transection and immediate repair. The facial function started to recover at 17 days in the placebo group and 14 days in the BDNF group. BDNF group had shorter period of increased GAP-43 mRNA expression than the placebo group. Topically applied BDNF may accelerate the facial nerve regeneration.

Purpose: To quantitatively assess pupillary functions after small pupil cataract surgery using the flexible iris retractor., Methods: Subjects were 11 patients (12 eyes) with small pupils who underwent phacoemulsification and intraocular lens implantation. Pupils were enlarged using the flexible iris retractor intraoperatively, and postoperative iriscorder data were compared with the data of 20 normal controls who underwent standard phacoemulsification and intraocular lens implantation., Results: Although pupillary area before light stimulus did not differ between the groups, contraction rate after light stimulus was significantly lower in the small pupil group than in the normal controls. The velocity of contraction and dilation was also significantly slower in the small pupil group. Wider pupillary stretching during surgery resulted in deteriorated pupillary functions after surgery. Eyes of patients on long-term miotic therapy with pilocarpine showed poorer pupillary reaction postoperatively., Conclusion: Inappropriate use of the flexible iris retractor causes an atonic, chronically enlarged postoperative pupil. To avoid postoperative pupillary complications, miotic pupils should not be stretched to larger than a 5.0 x 5.0 mm square.

Growth inhibitory factor (GIF) is a small protein belonging to the metallothionein family that has the capacity to inhibit neuronal survival and neurite formation in vitro. This study was conducted to investigate the role of GIF in the brain afflicted with ischemic injury. We used the in situ hybridization technique and Northern blot analysis to study the changes in GIF messenger RNA (mRNA) expression in a rat focal ischemia model. On the first day, the expression tended to decrease in the hemisphere ipsilateral to the injury. It returned to normal levels on the second day except for the central area of the middle cerebral artery (MCA) territory. On the third and fourth day, the expression increased diffusely in the hemisphere of the affected side, including the subcortical area. Two weeks after ischemia, the GIF mRNA expression increased again but only in the peri-infarcted area. Down-regulation of GIF on the first day in the cortex ipsilateral to the infarction might promote neurite sprouting. The subsequent increase in GIF mRNA expression on the third and fourth day might be a symptom of neurons attempting to inhibit excessive neurite outgrowth, or to protect themselves against toxicity caused by oxygen radicals. The later increase in the limited area around the infarction may be related to astroglial reaction. Growth inhibitory factor may play an important role in regulating the central nervous system after ischemic insults.

Plasminogen activators (PAs) have been suggested to play a role in neuronal migration and glial cell proliferation in the developing CNS. Less is known, however, about the role of PAs in the mature nervous system. To elucidate the role of tissue type plasminogen activator (tPA) in the nervous system we used in situ hybridization to study the expression of tPA mRNA within the rat facial nucleus after facial nerve transection. We also studied the effect of MK-801 on tPA mRNA expression in order to investigate whether the previously reported N-methyl-D-aspartate (NMDA) receptor activation is involved in this model. tPA mRNA was expressed in the ipsilateral facial motoneurones from 6 h after injury. This expression continued for at least 2 weeks after facial nerve transection. Administration of MK-801 before axonal injury did not affect the expression of tPA mRNA in the facial nucleus. These data suggest that tPA might be involved in the regenerative process without NMDA receptor activation in mature facial neurones.

Growth inhibitory factor / metallothionein III (GIF / MT-III) is reported to have the unique property of suppressing neuronal survival and neurite promotion in vitro. We investigated changes in the expression of GIF mRNA within the facial nucleus using in situ hybridization as well as changes in the function of the facial nerve after nerve injury. Following crushing injury just distal to the stylomastoid foramen, movement of the ipsilateral whiskers was eliminated but returned by the 7th day. GIF mRNA expression decreased at 3 days after injury and returned in 7 days. However, when the nerve was cut and sutured immediately, it took one month for the facial function to recover. In this case, GIF mRNA expression decreased 3 days after injury, remained at a low level for 14 days, and finally returned in 3-4 weeks. Thus, changes in the expression of GIF mRNA were found to be closely related to the facial nerve function.

Myo-inositol is one of the major organic osmolytes in the brain. It is accumulated into cells through an Na+/ myo-inositol cotransporter (SMIT) that is regulated by extracellular tonicity. To investigate the role of SMIT in the brain after cerebral ischemia, we examined expression of SMIT mRNA in the rat brain after middle cerebral artery occlusion, which would reflect alteration of extracellular tonicity. The expression of SMIT mRNA was markedly increased 12 h after surgery in the cortex of the affected side and lasted until the second day. Increased expression was also found in the contralateral cingulate cortex. Up-regulated expression was found predominantly in the neurons in remote areas, although nonneuronal cells adjacent to the ischemic core also expressed this mRNA. These results suggest that cerebral ischemia causes extensive osmotic stress in brain and that the neuronal cells respond to this stress by increasing SMIT expression.

Expression of glutamate/aspartate transporter (GLAST/GluT-1) was investigated in the axotomized facial nucleus by in-situ hybridization. Hybridization signals for GLAST mRNA were almost undetectable in the facial nucleus of sham-operated animals. However, the hybridization signals were seen from 3 days after facial nerve transection onward in the nucleus of the affected side. These signals lasted at least 5 weeks. Microautoradiograms showed that small non-neuronal cells in the ipsilateral facial nucleus expressed signals of GLAST mRNA after axotomy. These findings suggest that non-neuronal cells, presumably astrocytes, may protect axotomized motor neurons against glutamate toxicity via up-regulation of GLAST in the facial nucleus.

We examined the hypoxic tolerance phenomenon in vitro. Brief exposure to hypoxia induced the production of basic fibroblast growth factor (bFGF) mRNA and protein in rat cortical neurons and protected them from hypoxic injury. Cortical neurons were cultured from 18th-day rat embryos in a serum-free medium and subjected to brief (4 h) and/or prolonged (24 h) hypoxia. Neuronal damage was assessed by quantifying lactate dehydrogenase (LDH) activity in the medium. After brief hypoxia, LDH release was identical to that of the controls, whereas prolonged hypoxia caused a significant increase in LDH release, indicating neuronal death. However, if brief hypoxia was applied 2 days prior to the prolonged hypoxia, no increase in LDH release was observed. The bFGF mRNA expression was assessed with Northern blot and protein immunoreactivity with Western blot analysis. The brief period of hypoxia caused a 2.5-fold increase in bFGF mRNA and considerable bFGF protein expression 1 day later, but prolonged hypoxia caused increase in the expression of bFGF mRNA at 2 days and no protein expression until 3 days after the start of the hypoxia. When cells were subjected to prolonged hypoxia 2 days after brief hypoxia, however, no increase in bFGF mRNA was observed, while bFGF protein was expressed continuously. We also observed that exogenously applied bFGF reduced neuronal injury produced by prolonged hypoxia. The results obtained with this model suggest that brief hypoxia induces bFGF protein and thus tolerance to subsequent lethal hypoxia. Basic FGF might play a role as a tolerance-associated factor in this process. Thus, an in vitro model is useful for assessing the response of cortical neurons to hypoxic stress and for researching new factors related to ischemic tolerance.

Growth inhibitory factor (GIF) inhibits survival and neurite formation of cortical neurons in vitro and is found abundantly in the normal human brain. The role of GIF is still obscure, although it is reported to decrease in the brain in Alzheimer's disease. We examined changes in GIF mRNA expression in a rat cortical-ablation model with the aid of an in situ hybridization technique. In sham-operated animals, the GIF mRNA was expressed consistently in the cerebral cortex, hippocampus, and thalamus. One day after cortical ablation of the left somatosensory cortex, the expression tended to decrease in the cortex ipsilateral to the injury. Four days after surgery, it increased markedly in the affected cortex and thereafter returned to the level of the control animals except for the area surrounding the injury, where GIF mRNA again increased 2 to 3 weeks after ablation. The transient increase in GIF mRNA expression may reflect efforts to inhibit excessive sprouting of neurites. We also studied the effect of topically applied basic fibroblast growth factor (bFGF), which has a range of neurotrophic effects, on GIF mRNA expression. Topically applied bFGF enhanced the suppression of GIF at 1 day after surgery, though it did not affect the subsequent response. GIF can therefore be assumed to affect the outgrowth of injured neurites and might play a major role in maintenance of the neuronal network in cooperation with other trophic factors. Modification of these factors may be the key to improve neuronal damage after injury.

We investigated growth inhibitory factor (GIF) mRNA expression within the rat facial nucleus with the aid of in situ hybridization. We found that GIF mRNA was expressed abundantly in the facial motoneurons of sham operated animals, and that this gene expression decreased after transection of the facial nerve. This decrease of GIF mRNA was first detected on the third day and was maintained for at least five weeks after transection of the nerve. Changes in c-jun, an immediate early gene, were also investigated with this model, and it was found that c-jun mRNA started to increase in the facial nucleus on the first day and that this increase was maintained for at least 5 weeks. These results suggest that the facial motoneurons, when their axons are transected, continuously respond to the injury and that GIF mRNA is actively suppressed to reduce the inhibition of neurite outgrowth in order to regenerate the axons.

Expression of c-fos mRNA after cortical injury was studied using the in situ hybridization technique. Strong signals for c-fos mRNA were observed immediately after cortical ablation in neurons throughout the cortex ipsilateral to the injury. However, this c-fos mRNA expression was transient and disappeared within 6 h after the injury. When basic fibroblast growth factor (bFGF; 1 micrograms) was applied to the site of ablation, c-fos mRNA signals were observed for a much longer period. Even 24 h after injury, diffuse expression of c-fos mRNA was detected throughout the cortex, being mainly confined to non-neuronal cells. Intraperitoneal injection of MK-801 (3 mg/kg), a non-competitive NMDA receptor antagonist, suppressed the expression of c-fos mRNA after cortical ablation. It suppressed both the immediate and late expression induced by cortical ablation and bFGF. The immediate expression of c-fos in neurons is likely to be due to spreading depression, while neuronal-glial interactions would be involved in the mechanism of late c-fos expression by non-neuronal cells. Our results suggest that induction of c-fos after cortical injury can be modulated by topically applied bFGF and that the N-methyl-D-aspartate (NMDA) receptor is involved in c-fos expression not only caused by injury itself but also induced by injury and bFGF. As the immediate early genes regulate secondary gene responses, the induction of c-fos may contribute to neuronal plasticity and bFGF may enhance its effect.