Intermittent gait disturbance in idiopathic normal pressure hydrocephalus.

OBJECTIVES: We identified intermittent gait disturbance (IGD) observed in the mild stage of idiopathic normal pressure hydrocephalus (iNPH). The first purpose of this study was to clarify the temporal gait profile of IGD during long-distance gait. The second purpose was to confirm the difference in treatment effect after cerebrospinal fluid (CSF) shunting in patients with and without IGD. MATERIALS AND METHODS: Fourteen consecutive iNPH patients with mild gait disturbance with a timed up-and-go (TUG) of <20 seconds were prospectively enrolled in the study. All patients were asked "Do you experience gait difficulty after over five minutes of walking?" Seven "yes" patients formed the IGD group, and seven "no" patients formed the persistent gait disturbance (PGD) group. One day before and 7 days after CSF shunting, gait function was evaluated by the 6-minute walk test (6MWT) and TUG. RESULTS: Preoperatively, all patients in the IGD group demonstrated features of IGD during the 6MWT, characterized by a progressive pattern of decreased gait speed and step length with increased cadence and absence of leg pain. Post-operatively, these features of IGD improved in all patients. In the PGD group, preoperative walking did not significantly worsen during the 6MWT and did not significantly change 7 days after treatment. Improvement of gait symptoms 1 week after CSF shunting could be detected with 6MWT instead of TUG. CONCLUSIONS: Intermittent gait disturbance is not a rare symptom in mild stage of iNPH and may serve as an important clinical diagnostic marker for identifying mild iNPH patients.

Intraoperative 5-aminolevulinic acid-induced photodynamic diagnosis of metastatic brain tumors with histopathological analysis.

BACKGROUND: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors. METHODS: We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection. Patients were given 20 mg/kg of 5-ALA orally 2 h prior to the surgery. High-powered excitation illumination and a low-pass filter (420, 450, or 500 nm) were used to visualize the fluorescence of protoporphyrin IX (PpIX), the 5-ALA metabolite. We evaluated the relationships between the fluorescence and histopathological findings in both tumoral and peritumoral brain tissue. RESULTS: Tumoral PpIX fluorescence was seen in only 5 patients (31%); in the remaining 11 patients (69%), there was no fluorescence in the tumor bulk itself. In 14 patients (86%), vague fluorescence was seen in peritumoral brain tissue, at a thickness of 2-6 mm. The histopathological examination found cancer cell invasion of adjacent brain tissue in 75% of patients (12/16), at a mean ± SD depth of 1.4 ± 1.0 mm (range 0.2-3.4 mm) from the microscopic border of the tumor. There was a moderate correlation between vague fluorescence in adjacent brain tissue and the depth of cancer cell invasion (P = 0.004). CONCLUSION: Peritumoral fluorescence may be a good intraoperative indicator of tumor extent, preceding more complete microscopic gross total resection. TRIAL REGISTRATION: Institutional Review Board of Osaka Medical College No. 42, registered February 17, 1998, and No. 300, registered April 1, 2008. They were retrospectively registered.

In not only vertebroplasty but also kyphoplasty, the resolution of vertebral deformities depends on vertebral mobility.

BACKGROUND AND PURPOSE: It has not been clarified whether the postoperative resolution of vertebral deformities achieved by KP are superior to those achieved by VP. We compared the outcomes of KP and VP, taking into account the presence of vertebral mobility, to determine whether the balloon inflation in KP may contribute to postoperative resolution of the vertebral deformities in patients with VCFs. MATERIALS AND METHODS: The subjects had 34 vertebral bodies treated by VP, and 43 vertebral bodies treated by KP. In all patients, preoperative dynamic imaging was performed to assess the presence of vertebral mobility. First, the vertebral height restoration and kyphotic change were compared between the VP and KP groups. Then, the patients were further divided into 2 groups on the basis of the presence of vertebral mobility, and they were compared within and between the VP and KP groups in relation to the presence of vertebral mobility. RESULTS: Overall, no significant differences were observed in either the vertebral height restoration or kyphotic change between the VP and KP groups (P > .20). Preoperative dynamic imaging identified 19 vertebral bodies each with vertebral mobility in the VP (56%) and KP groups (44%) (P = .21). Within the VP and KP groups, the vertebral height restoration and kyphotic changes were significantly better in patients with vertebral mobility than in those without (P < .01). There were no significant differences between the 2 treatment groups after adjustment for the presence of vertebral mobility (P > .30). CONCLUSIONS: In both the VP and KP groups, the vertebral height restoration and kyphotic change largely depended on the preoperative vertebral mobility. The use of the balloon itself contributed little to resolution of the vertebral deformities.

Validity of intervertebral bone cement infusion for painful vertebral compression fractures based on the presence of vertebral mobility.

BACKGROUND AND PURPOSE: It is uncertain whether analgesic effects of vertebroplasty in patients with painful VCF are actually attributable to intervertebral cement infusion. This study aims to assess the validity of cement infusion performed for pain relief based on the presence or absence of pseudoarthrosis. MATERIALS AND METHODS: We compared therapeutic effects between PVP and vertebral perforation without bone cement infusion in patients with painful VCF. The subjects were 64 patients undergoing PVP (PVP group) and 67 undergoing vertebral perforation (perforation group). In all patients, preoperative dynamic radiography was performed to assess the presence of vertebral mobility. Patients were classified into 2 groups, those with and those without vertebral mobility, and changes in VAS and ADL scores before and after surgery were compared between the PVP and perforation groups. RESULTS: Regarding patients with vertebral mobility, VAS improved during the 3 months immediately after surgery in the PVP group compared with the perforation group (P < .05). Although no significant difference in postoperative ADL scores was observed between the 2 treatment groups, the scores 3 months after surgery were better in the PVP group than in the perforation group. Meanwhile, in the subgroup of patients without vertebral mobility, both treatments produced marked pain relief, but the difference was not significant (P > .05). Moreover, there was no difference in ADL scores between the 2 treatment groups. CONCLUSIONS: Intervertebral cement infusion exerts analgesic effects in patients with VCF with pseudoarthrosis. However, in those without vertebral mobility, the analgesic effects of vertebroplasty are the same regardless of bone cement infusion.

Comparative study of percutaneous vertebral body perforation and vertebroplasty for the treatment of painful vertebral compression fractures.

BACKGROUND AND PURPOSE: Percutaneous vertebral body perforation is a new technique for treating painful VCFs. Herein, we compare the therapeutic effect of vertebral perforation and conventional vertebroplasty for treating VCFs. MATERIALS AND METHODS: One hundred eight patients with single painful VCFs were assigned to undergo vertebral perforation (perforation group) or vertebroplasty (PVP group). Clinical outcomes were assessed by using the VAS. The associations of analgesic effect and clinical factors were also analyzed by multivariate regression. Plain radiographs were used to quantify the progression of vertebral body compression after surgery and to evaluate cement leakage and new vertebral fractures. The median follow-up time was 10 months. RESULTS: Baseline characteristics were similar in the 2 groups. No factors correlated with analgesic effects in the PVP group. The analgesic effect of vertebral perforation was, however, related to the preoperative severity of vertebral compression and was low in patients with severe deformity (P < .05). Among patients with preoperative vertebral percentage of compression below 30%, there were no significant differences between the 2 groups in analgesic effect at any postoperative intervals. Progression of vertebral compression after surgery occurred in 22.2% and 16.0% of treated vertebrae in the perforation and PVP groups, respectively (P = .38). Respectively, 3.7% and 20.0% of the perforation and PVP groups had new postoperative fractures during follow-up (P < .05). There were no other complications. CONCLUSIONS: Vertebral perforation was safe and effective for painful VCFs with slight compression. However, vertebroplasty should be considered for patients with marked vertebral body compression.

Effect of intrauterine infusion with liquid paraffin on phagocytes migrating to mucus of external os of the cervix in cows.

The objective of this study was to investigate the effect of intrauterine infusion with liquid paraffin (LP) on phagocytic migration into the uterus of cows. Smears of swab samples of the external os of the cervix and discharges collected inside the vagina were obtained in multiparous dairy cows (n = 10) that had been infused with 50 ml of LP (LP group: n = 5) or physiological saline (PS group: n = 5) on day 10 or 11 after ovulation (day 0: ovulation). The samples were collected for cytological examination 0 (just before), 0.25, 1, 2, 3, 4, 6, 8, 12 and 24 h after LP or PS infusion and then at daily intervals until subsequent ovulation. The number of neutrophils increased significantly (p < 0.05) for 8 days compared with the pre-infusion level in the LP group and for 2 days in the PS group. The average numbers of neutrophils in the LP group were significantly (p < 0.05) greater than those in the PS group on 3, 4, 5 and 8 days after infusion. The number of monocytes from 6 h to 8 days after LP infusion was significantly higher than that before infusion (p < 0.05). The average numbers of monocytes at 4 and 6 h and 1 day after infusion in the LP group were significantly higher than those in the PS group. These findings indicate that LP stimulates phagocytic migration into the uterine lumen in cows and that LP infusion into the uterus might enhance uterine defence mechanisms during uterine infection.

Formation of biocompatible nanoparticles via the self-assembly of chitosan and modified lecithin.

The formation of biocompatible nanoparticles via the self-assembly of chitosan (CHI) and modified lecithin (ML) was studied. Stable nanoparticles in the size range of 123 to 350 nm were formed at over a wide molar mixing ratios of CHI/ML solutions (amino group/phosphate group) (NH(3) (+)/PO(3) (-)) and total polyelectrolyte (PE) concentrations (0.1 to 1 wt%) except at intermediate molar ratios when the surface charge was close to neutrality. Zeta-potentials of the nanoparticles were found to be independent of the total PE concentrations. Nanoparticles exhibited excellent stability at over an extended pH (pHs 3 to 6) and ionic strength range (< or = 500 mM NaCl concentration). The particle size and zeta-potential of the nanoparticles increased with the molecular weight of CHI. Transmission electron microscopy suggested that nanoparticles were generally spherical in shape with CHI constituting the exterior of its surface at high molar mixing ratios. Dextran-fluorescein isothiocyanate, bovine serum albumin, and Coomassie brilliant blue as models of nonionic, positively and negatively charged compounds were encapsulated within the nanoparticles at between 8.7% and 62.7% efficiency. The ability of the nanoparticle suspensions to be converted to lyophilized powder or concentrated suspension was also demonstrated.

Vesicle, mitochondrial, and plastid division machineries with emphasis on dynamin and electron-dense rings.

The original eukaryotic cells contained at least one set of double-membrane-bounded organelles (cell nucleus and mitochondria) and single-membrane-bounded organelles [endoplasmic reticulum, Golgi apparatus, lysosomes (vacuoles), and microbodies (peroxisomes)]. An increase in the number of organelles accompanied the evolution of these cells into Amoebozoa and Opisthokonta. Furthermore, the basic cells, containing mitochondria, engulfed photosynthetic Cyanobacteria, which were converted to plastids, and the cells thereby evolved into cells characteristic of the Bikonta. How did basic single- and double-membrane-bounded organelles originate from bacteria-like cells during early eukaryotic evolution? To answer this question, the important roles of the GTPase dynamin- and electron-dense rings in the promotion of diverse cellular activities in eukaryotes, including endocytosis, vesicular transport, mitochondrial division, and plastid division, must be considered. In this review, vesicle division, mitochondrial division, and plastid division machineries, including the dynamin- and electron-dense rings, and their roles in the origin and biogenesis of organelles in eukaryote cells are summarized.

Neurological deficits and brain edema after intracerebral hemorrhage in Mongolian gerbils.

We examined the time course of neurological deficits in gerbils after an intracerebral hemorrhage (ICH) induced by autologous blood infusion and examined its correlation with the severity of perihematomal edema. Mongolian gerbils (n = 15) were subjected to stereotaxic autologous blood infusion (30 or 60 microL) into the left caudate nucleus. Corner-turn and forelimb-placing tests were performed before, and 1 and 3 days after ICH. Perihematomal water content was measured by tissue gravimetry. Gerbils developed neurological deficits and perihematomal edema at day 1 after ICH. Both neurological deficits and perihematomal edema were significantly greater in animals with 60 microL blood infusion compared to the 30 microL infusion group, and both neurological deficits and edema were also greater at 3 days compared to 1 day after ICH. The severity of neurological deficits paralleled the degree of perihematomal edema. We conclude that the Mongolian gerbil is a suitable model for studies on the behavioral effects of ICH.

Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation.

OBJECTIVE: IL-19 is a novel cytokine of the IL-10 family. In this study, we sought to examine whether IL-19 plays a role in the pathogenesis of RA. METHODS: Expression of IL-19, IL-20 receptor 1 (IL-20R1) and IL-20R2 was examined by RT-PCR and immunohistochemical analysis in rheumatoid synovium. The effects of IL-19 on synovial cells established from rheumatoid synovium (RASCs), with regard to IL-6 production and signal transducers and activators of transcription3 (STAT3) activation, were examined by ELISA and western blot analysis, respectively. The effect of IL-19 on RASC apoptosis was examined by Hoechst staining, flow cytometry analysis of annexin V binding and caspase-3 activity. RESULTS: IL-19, IL-20R1 and IL-20R2 mRNA were detected by RT-PCR in synovial tissues from RA patients. Immunohistochemical analysis showed IL-19 was predominantly expressed in the hyperplastic lining layers of RA synovial tissues. The majority of IL-19-positive cells were vimentin-positive and CD68-positive synovial cells, serving as markers of fibroblasts and macrophages, respectively. IL-20R1 and IL-20R2 (IL-20Rs) were expressed in both the lining and sublining layers of RA synovium. In RASC, IL-19 was induced by lipopolysaccharide stimulation and constitutive expression of IL-20Rs was observed, suggesting IL-19 has an autocrine action. In terms of this function, IL-19 induced STAT3 activation and increased IL-6 production by RASC above the medium control. Moreover, IL-19 significantly reduced RASC apoptosis induced by serum starvation. CONCLUSIONS: These data suggest that IL-19, produced by synovial cells, promotes joint inflammation in RA by inducing IL-6 production and decreasing synovial cell apoptosis.

Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions.

OBJECTIVES: To determine if the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of lupus nephritis (LN) is helpful in predicting renal outcome. METHODS: A total of 92 patients with LN who underwent renal biopsy in our hospital were re-classified according to the ISN/RPS 2003 criteria. RESULTS: The mean patient age was 36.8 yrs and the median observation period was 65 months. The relative frequency for each class was as follows: Class I (minimal mesangial LN) 0%, Class II (mesangial proliferative LN) 13%, Class III (focal LN) 17%, Class IV (diffuse LN) 60% and Class V (membranous LN) 10%. Within Class IV, diffuse segmental (Class IV-S) was 25% and diffuse global (Class IV-G) 75%. During the observation period, renal function was more likely to deteriorate in Class IV-G cases than in Class IV-S cases. Importantly, when Class IV-G was subdivided into cases involving active lesion alone [IV-G (A)] or chronic lesion [IV-G (A/C)], the majority of cases in IV-G (A) was nephrotic, but responded well to therapy. In contrast, renal function declined only in IV-G (A/C) cases. Patients with Class IV-G (A/C) had persistent proteinuria in spite of intensified therapies. Moreover, the higher proportion of chronic lesions was related with the deterioration of renal function. CONCLUSIONS: This study showed that in Class IV-G cases, renal outcome differed in the presence of chronicity. Chronicity could be a critical factor in predicting outcome. Thus, the revised classification of LN is clinically valuable in identifying different renal outcomes among patients with diffuse LN.

Diffusion tensor imaging in chronic subdural hematoma: correlation between clinical signs and fractional anisotropy in the pyramidal tract.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) was introduced as a good technique to evaluate structural abnormalities in the white matter. In this study, we used DTI to examine anisotropic changes of the pyramidal tracts displaced by chronic subdural hematoma (CSDH). MATERIALS AND METHODS: Twenty-six patients with unilateral CSDH underwent DTI before and after surgery. We measured fractional anisotropy (FA) values in pyramidal tracts of bilateral cerebral peduncles and calculated the ratio of the FA value on the lesion side to that on the contralateral side (FA ratio) and compared the ratios with motor weakness. Moreover, the relationships between FA ratios and clinical factors such as age, sex, midline shift, interval from trauma, and hematoma attenuation on CT were evaluated. RESULTS: FA values of pyramidal tracts on the lesion side were significantly lower than those on the contralateral side (0.66 +/- 0.07 versus 0.74 +/- 0.05, P < .0001). The FA ratio was correlated to the severity of motor weakness (r(2) = 0.32, P = .002). FA ratios after surgery improved significantly compared with those before surgery (0.96 +/- 0.08 versus 0.89 +/- 0.07, P = .0004). Intervals from trauma and the midline shift were significantly associated with decreased FA ratios (P = .0008 and P = .037). CONCLUSIONS: In patients with CSDH, a reversible decrease of FA in the affected pyramidal tract on DTI was correlated to motor weakness. These anisotropic changes were considered to be caused by a reversible distortion of neuron fibers and vasogenic edema due to the hematoma.

Nestin expression in the kidney with an obstructed ureter.

Nestin is an intermediate filament protein originally identified in neuroepithelial stem cells. This cytoskeletal-associated protein is also expressed in some non-neuronal organs including renal tubular cells and glomerular endothelial cells during kidney development. Little is known, however, about nestin expression in the kidney during injury. In this study, we find nestin expression induced in renal tubular and interstitial myofibroblasts in the adult rat kidney following unilateral ureteral obstruction. The degree of nestin expression was well correlated with the degree of tubulointerstitial fibrosis. Immunohistochemical identification of specific nephron segments showed that nestin was primarily expressed by proximal tubules, partially by distal tubules and thick ascending limbs of Henle but not by collecting ducts. The nestin-positive tubular cells also expressed vimentin and heat-shock protein 47 (HSP47) suggesting these cells reverted to a mesenchymal phenotype. Not all vimentin- or HSP-expressing cells expressed nestin; however, suggesting that nestin is distinct from these conventional mesenchymal markers. Nestin expression was also found associated with phenotypical changes in cultured renal cells induced by hypoxia or transforming growth factor-beta. Nestin expression was located in hypoxic regions of the kidney with an obstructed ureter. Our results indicate that nestin could be a novel marker for tubulointerstitial injury.

Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis.

OBJECTIVES: To determine the safety and efficacy of a short course of fludarabine combined with cyclophoshamide in lupus nephritis. METHODS: A phase I/II open label pilot study. Thirteen patients with active proliferative lupus nephritis received monthly oral boluses of low-dose cyclophoshamide (0.5 gm/m(2) on day 1) and subcutaneous fludarabine (30 mg/m(2) on days 1-3) for 3-6 cycles. Concomitant prednisone was aggressively tapered from 0.5 mg/kg/day to a low-dose, alternate-day schedule. Patients were followed for at least 24 months after therapy. The primary outcome was the number of patients achieving renal remission defined as stable creatinine, proteinuria <1 gm/day and inactive urine sediment for at least 6 months. RESULTS: The study was terminated early because of bone marrow toxicity. Eleven patients who received at least three cycles were evaluated for efficacy. Ten patients improved markedly with seven patients achieving complete remission and three patients achieving partial remission. There were three serious haematological adverse events during the treatment with one death due to transfusion-associated graft vs host disease. Profound and prolonged CD4 (mean CD4: 98/microl at 7 months and 251/microl at 12 months) and CD20 lymphocytopenia was noted in most patients. Three patients developed Herpes zoster infections. CONCLUSIONS: A short course of low-dose fludarabine and cyclophoshamide can induce long-lasting remissions in patients with proliferative lupus nephritis, but severe myelosuppression limits its widespread use.

Stenting for chronic total occlusion of the proximal subclavian artery.

SUMMARY: We report the results of 26 patients who underwent stent deployment for chronic total occlusion of proximal subclavian artery. From January 1998 to October 2005, 26 patients (18 male; mean age, 62.7 years, range 22 to 83 years), 28 lesions, underwent 29 procedures of stenting for chronic total occlusion of the proximal subclavian artery.Twenty-three patients had symptoms of claudication in their arm, no patients had subclavian steal syndrome.A brachial approach was used in 21 procedures, a femoral approach was used in five procedures, and combined femoral-brachial approach was required in three procedures. Primary stent deployment was success in 24 lesions (85.7%), and secondary procedure was success in one patient, totally 25 lesions (89.3%) were successfully treated by stenting. Procedure related complication occurred in four cases, including stent migration without symptoms in two procedures, hemianopsia on next day in a case, and TIA on unclear reason in one case. Permanent morbidity rate is 3.4% in procedure. Target lesion re-treatment required in three lesions, caused by subacute thrombosis, in-stent-restenosis, and dissection of the vessel by stent edge. The cases of subacute thrombosis and in-stent-restenosis were treated by re-PTA, and the case of dissection was treated by additional stenting. Secondary patency was 100%. We conclude that stenting for chronic total occlusion of subclavian arteries appears feasible and safe.

MR imaging of human herpesvirus-6 encephalopathy after hematopoietic stem cell transplantation in adults.

BACKGROUND AND PURPOSE: Human herpesvirus-6 (HHV-6)-associated encephalopathy tends to develop in immunocompromised patients. Neurologic symptoms, such as disorientation, short-term memory loss, convulsion, coma, and hypopnea could occur, but they may be nonspecific. We retrospectively reviewed MR images of 6 adults with HHV-6-associated encephalopathy to study characteristic imaging findings that could be useful in making the diagnosis. MATERIALS AND METHODS: Between 2003 and 2005, we encountered 6 cases of HHV-6-associated encephalopathy (3 men and 3 women; age range, 36-55 years) in 3 hospitals. The diagnosis was made clinically according to the neurologic symptoms accompanied by high-level copies of HHV-6 DNA in CSF or peripheral blood by quantitative polymerase chain reaction without the detection of any other infectious pathogen. RESULTS: All 6 patients had abnormal hippocampus/amygdala findings on presentation, and no other regions were involved. In the early period (0-2 days from onset), abnormal high signal intensity on fluid-attenuated inversion recovery (FLAIR) imaging (2 of 3, 67%) and on diffusion-weighted images accompanied by apparent diffusion coefficient (ADC) reduction (2 of 2, 100%) were observed. In the middle period (3-30 days), abnormal low signal intensity on T1-weighted images (5 of 6, 83%) and abnormal high signal intensity on T2-weighted images (4 of 6, 67%) and FLAIR (5 of 6, 83%) were confirmed. In the late period (> 30 days), we saw the resolution of signal intensity abnormalities and the appearance of atrophic change (4 of 4, 100%) of the affected regions. CONCLUSION: HHV-6-associated encephalopathy in adults tends to affect the mesial temporal lobe. MR imaging is useful for detecting HHV-6 encephalopathy and distinguishing it from the other diseases of the central nervous system in immunocompromised patients.

Complete elimination of maternal mitochondrial DNA during meiosis resulting in the paternal inheritance of the mitochondrial genome in Chlamydomonas species.

The non-Mendelian inheritance of organellar DNA is common in most plants and animals. In the isogamous green alga Chlamydomonas species, progeny inherit chloroplast genes from the maternal parent, as paternal chloroplast genes are selectively eliminated in young zygotes. Mitochondrial genes are inherited from the paternal parent. Analogically, maternal mitochondrial DNA (mtDNA) is thought to be selectively eliminated. Nevertheless, it is unclear when this selective elimination occurs. Here, we examined the behaviors of maternal and paternal mtDNAs by various methods during the period between the beginning of zygote formation and zoospore formation. First, we observed the behavior of the organelle nucleoids of living cells by specifically staining DNA with the fluorochrome SYBR Green I and staining mitochondria with 3,3'-dihexyloxacarbocyanine iodide. We also examined the fate of mtDNA of male and female parental origin by real-time PCR, nested PCR with single zygotes, and fluorescence in situ hybridization analysis. The mtDNA of maternal origin was completely eliminated before the first cell nuclear division, probably just before mtDNA synthesis, during meiosis. Therefore, the progeny inherit the remaining paternal mtDNA. We suggest that the complete elimination of maternal mtDNA during meiosis is the primary cause of paternal mitochondrial inheritance.

Unilateral spatial neglect and memory deficit associated with abnormal beta-amyloid precursor protein accumulation after lateral fluid percussion injury in Mongolian gerbils.

The purpose of this study was to investigate cognitive/memory dysfunctions and the pathological process contributing to such dysfunction following moderate lateral fluid percussion injury (LFPI) in Mongolian gerbils. Mongolian gerbils were subjected to moderate LFPI (1.3 1.6 atm). During 7 days post-trauma, spatial cognitive and memory dysfunctions were evaluated by T-maze test (TMT). At 6 hours, 24 hours, and 7 days post-injury, animals were sacrificed and the brains were prepared for Kluver-Barrera staining and immunostaining of beta-amyloid precursor protein (APP). In LFPI animals, the spontaneous alternation rate in the TMT remained below the random alternation rate (< 50%) on all post-injury test days. These animals also showed a transient tendency to choose only the right arm (ipsilateral to the injury) in the TMT at 6 hours and 24 hours after injury. Significant accumulation of APP was found widespread in the ipsilateral hemisphere including directly injured cortex, subcortical white matter, and hippocampal formation at 6 hours and 24 hours post-injury, while on day 7, the increased immunoreactivity of APP subsided. These results suggest that the widespread axonal degeneration of the white matter might contribute to the unilateral spatial neglect and memory deficit in the acute stage after LFPI.

Diffusion tensor feature in vasogenic brain edema in cats.

We investigated the correlation between the changes in diffusion tensor magnetic resonance imaging, regional water content, and tissue ultrastructure after vasogenic brain edema induced by cortical cold lesioning. In this cat model, E3 in the white matter was dominantly increased while fractional anisotropy (FA) was significantly decreased 8 hours after cortical cold lesioning. This finding indicates that water diffusion in the cortical white matter mainly increased perpendicularly rather than parallel to the direction of the nerve fibers. Additionally, in the area where edema is mild or moderate (tissues with water content of 65% to 75%), FA in the chronic phase was significantly lower than that in the acute phase. Histological examination demonstrated disordered arrangement of nerve fibers, highly dissociated neuronal fibers due to extracellular accumulation of protein rich-fluid, and enlarged interfiber spaces in the acute phase.

Restitution of ischemic injuries in penumbra of cerebral cortex after temporary ischemia.

We investigated, at both light and ultrastructural levels, the fate of swollen astrocytes and remodeling of neurites connected to disseminated, dying neurons in the ischemic neocortical penumbra. Specimens from left cerebral cortex were cut coronally at the infundibulum and observed by light and electron microscopy. We measured synapses and spines, and the thickness of neuritic trunks in the neuropil on electron microscopy photos. We also determined percent volume of axon terminals and spines by Weibel's point-counting method. Astrocytic swelling gradually subsided from day 4 after the ischemic insult, with increases in cytoplasmic glial fibrils and GFAP-positive astrocytes. Disseminated dying electron-dense neurons were fragmented by invading astrocytic cell processes and accumulated as granular pieces. The number of synapses and spines and total percent volume of axon terminals and spines decreased with an increasing sparsity of synaptic vesicles until day 4. One to 12 weeks after the ischemic insult, these values increased to or exceeded control values, and sprouting and increased synaptic vesicles were seen. Axons that had been attached to the dying neurons appeared to have shifted their connections to the spines and the neurites of the surviving neurons, increasing their thickness. Astrocytic restitution and neuronal remodeling processes started at 4 days continuing until 12 weeks after ischemic insult.