Lymphoepithelial carcinoma in the sublingual gland.

Lymphoepithelial carcinoma is rare in the salivary glands, with an incidence of 0.4%. The most commonly affected site is the parotid gland, followed by the submandibular gland. Lymphoepithelial carcinoma in the sublingual gland has been reported only four times in the existing English-language literature. Such tumours are characterized by the presence of a poorly differentiated carcinoma that is surrounded and infiltrated by lymphocytes, and they are strongly associated with Epstein-Barr virus infection, patient ethnicity, and prominent radiosensitivity. Wide surgical excision combined with adjuvant therapy has been suggested as the first-choice therapeutic regimen. This report describes the case of a 34-year-old Indonesian woman who was evaluated and treated in Taipei Medical University Hospital. She had a tumour that presented as a painless swelling on the floor of the mouth. The diagnosis was confirmed by conducting an incisional biopsy, and a wide surgical excision with bilateral supraomohyoid neck dissection and free flap reconstruction was performed. The patient also underwent adjuvant chemoradiotherapy. No evidence of local recurrence or distant metastasis was detected during the 6 months of follow-up. Subsequently, the patient returned to her home country, and further follow-ups were not conducted.

[A dose-response meta-analysis on the relationship between daily tea intake and cardiovascular mortality based on the GRADE system].

Objective: To explore the relationship between daily tea intake and cardiovascular disease (CVD) mortality. Methods: PubMed, EMbase, The Cochrane, Chinese Biomedical Literature Database, CNKI, and Wanfang Database were searched to collect research on tea intake and CVD mortality. The search period was from the establishment of the database to June 2020. Two researchers independently screened and extracted literature. The risk of bias was evaluated in the included studies, a dose-response meta-analysis was conducted, sensitivity analysis and publication bias analysis of the research results, and quality evaluation of the included literature and GRADE classification of the evidence body were performed. Results: A total of 21 cohort or case-control studies were included, including 1 304 978 subjects. Among them, 38 222 deaths from CVD were reported. The quality scores of the included studies were all ≥ 6 points. The dose-response meta-analysis showed that for every additional cup of tea intake per day, the mortality rate of CVD decreased by about 3% (95%CI 0.95-0.98, P<0.05), and there was a non-linear dose-response relationship (P<0.05). Compared with people who do not drink tea, people who drink 1 to 8 cups of tea a day have 8% lower CVD mortality (RR=0.92, 95%CI 0.89-0.95), 13% (RR=0.87, 95 %CI 0.84-0.91), 15% (RR=0.85, 95%CI 0.82-0.89), 15% (RR=0.85, 95%CI 0.81-0.89), 16% (RR=0.84, 95%CI 0.80-0.89), 16% (RR=0.84, 95%CI 0.81-0.88), 16% (RR=0.84, 95%CI 0.81-0.87), 16% (RR=0.84, 95%CI 0.80-0.88), respectively. The results of traditional meta-analysis showed that compared with people who do not drink tea, people who drink more than 1 cup of tea a day are associated with 14% lower CVD mortality rate (RR=0.86, 95%CI 0.81-0.91, I2=73.2%, P<0.05). The results of subgroup analysis showed that compared with the corresponding people who did not drink tea, men who drank more than 1 cup of tea a day reduced the CVD mortality rate by 24%, women by 14%, European and American populations by 12%, and Asian populations by 15%. The population who consumed green tea decreased CVD mortality by 15%, and the population of non-smokers decreased CVD mortality by 20% (all P<0.05). The population who consumed black tea decreased CVD mortality by 8%, and the smoking population who consumed black tea decreased CVD mortality by 3%, and the difference was not statistically significant (all P>0.05). The results of the bias analysis showed that Begg=0.42 and Egger=0.62, indicating that the distribution on both sides of the funnel chart is symmetrical, suggesting that there is no publication bias. The results of sensitivity analysis showed that the effect size of the outcome index did not change significantly after excluding any article, indicating that the results are robust and credible. The GRADE evaluation showed that the evidence grades of the outcome indicators were all low grade. Conclusions: Daily tea consumption is related to reduced CVD mortality. It is therefore recommended to drink an appropriate amount of tea daily.

Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression, by Y.-Q. Gao, H.-Y. Cheng, K.-F. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3621-3626-DOI: 10.26355/eurrev_201905_17785-PMID: 31114986" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17785.

Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression.

OBJECTIVE: Recent studies have revealed the important role of long non-coding RNA (lncRNAs) in the development of malignant tumors. In this work, we explored the exact role of lncRNA DANCR in ovarian cancer progression and the underlying mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect DANCR expression in both ovarian cancer cells and tissue samples. Subsequently, cell proliferation assay and transwell assay were conducted. Furthermore, the underlying mechanism was explored via qRT-PCR and Western blot assay. RESULTS: The expression of DANCR in ovarian cancer samples was significantly higher than that of the corresponding normal tissues. After DANCR overexpression in vitro, the proliferation, invasion and migration of ovarian cancer cells were markedly promoted. In addition, both the mRNA and protein expression levels of insulin-like growth factor 2 (IGF2) were remarkably upregulated after DANCR overexpression. Furthermore, the results found that the expression level of IGF2 was positively correlated with DANCR expression in ovarian cancer tissues. CONCLUSIONS: In this study, we revealed that DANCR could enhance the proliferation, migration and invasion capacities of ovarian cancer cells by upregulating IGF2. Our findings might offer a potential therapeutic choice for patients with ovarian cancer.

Effects of siRNA-mediated silencing of Sal-like 4 expression on proliferation and apoptosis of prostate cancer C4-2 cells.

The aim of this study was to evaluate the effects of small interfering RNA (siRNA)-inhibited expression of the Sal-like 4 (SALL4) gene on the proliferation, colony formation, and apoptosis of prostate cancer C4-2 cells. C4-2 cells were cultured and divided into a si-SALL4 group, a negative control siRNA group, and a blank control group. SALL4 mRNA levels and protein expression were detected by real-time polymerase chain reaction and western blot, respectively. Changes in the cell proliferation and colony formation capacities were observed by using the MTS colorimetric method and colony formation assay, respectively. The influence of SALL4 on apoptosis was assessed with flow cytometry, and the expression of apoptosis-related proteins B-cell lymphoma 2 (Bcl-2) and bcl-like-protein 4 (Bax) were detected by western blot. The si-SALL4 group had significantly lower mRNA and protein levels of SALL4 as well as decreased proliferation and colony formation capacities than the negative control group (P < 0.05). There were significantly more apoptotic cells in the si-SALL4 group compared to the negative control (P < 0.05), and the expression of Bcl-2 and Bax decreased and increased, respectively, after treatment with si-SALL4. Silencing SALL4 expression by using siRNA technology inhibited the proliferation and colony formation of C4-2 cells, and promoted apoptosis likely mediated by Bcl-2 and Bax expression. These results provide experimental basis for further elucidating the role of SALL4 in prostate cancer cells.

The impact of LH, E2, and P level of HCG administration day on outcomes of in vitro fertilization in controlled ovarian hyperstimulation.

OBJECTIVES: The objective of this study was to evaluate the impact of luteinizing hormone (LH), estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) administration on outcomes of in vitro fertilization (IVF) in controlled ovarian hyperstimulation (COH). STUDY DESIGN: In this retrospective study, 129 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments were included; these cycles were stratified according to LH levels of ≥ 1.12 IU/L or < 1.12 U/L and according to E2 levels of ≥ 1,005.89 pmol/L or < 1,005.89 pmol/L. The main outcome measure was the clinical pregnancy rate. RESULTS: The clinical pregnancy rate was significantly higher in the group with LH ≥ 1.12 IU/L than in the group with LH < 1.12 U/L (43.28% vs. 30.65%, p < 0.05). The clinical pregnancy rate was also higher in the group with E2 ≥ 1,005.89 pmol/L than in the group with average E2 < 1,005.89 pmol/L (42.86% vs. 30.51%, p < 0.05). Among the LH, E2, and P levels on the day of HCG administration, LH level was the most important predictor of outcomes of IVF in COH. The present data showed an adverse effect of low serum LH level (LH < 1.12 IU/L) on the day of HCG administration on clinical pregnancy rate. E2 level can also predict the outcomes of IVF in COH. CONCLUSIONS: Low serum LH level (LH < 1.12 IU/L) and low serum E2 level (average E2 < 1,005.89 pmol/L) on the day of HCG administration led to low clinical pregnancy rates, while the P level on the day of HCG administration may have had little effect on clinical pregnancy.

A combined compensation method for the output voltage of an insulated core transformer power supply.

An insulated core transformer (ICT) power supply is an ideal high-voltage generator for irradiation accelerators with energy lower than 3 MeV. However, there is a significant problem that the structure of the segmented cores leads to an increase in the leakage flux and voltage differences between rectifier disks. A high level of consistency in the output of the disks helps to achieve a compact structure by improving the utilization of both the rectifier components and the insulation distances, and consequently increase the output voltage of the power supply. The output voltages of the disks which are far away from the primary coils need to be improved to reduce their inhomogeneity. In this study, by investigating and comparing the existing compensation methods, a new combined compensation method is proposed, which increases the turns on the secondary coils and employs parallel capacitors to improve the consistency of the disks, while covering the entire operating range of the power supply. This method turns out to be both feasible and effective during the development of an ICT power supply. The non-uniformity of the output voltages of the disks is less than 3.5% from no-load to full-load, and the power supply reaches an output specification of 350 kV/60 mA.

Construction of integrated genetic linkage maps of the tiger shrimp (Penaeus monodon) using microsatellite and AFLP markers.

The linkage maps of male and female tiger shrimp (P. monodon) were constructed based on 256 microsatellite and 85 amplified fragment length polymorphism (AFLP) markers. Microsatellite markers obtained from clone sequences of partial genomic libraries, tandem repeat sequences from databases and previous publications and fosmid end sequences were employed. Of 670 microsatellite and 158 AFLP markers tested for polymorphism, 341 (256 microsatellite and 85 AFLP markers) were used for genotyping with three F(1) mapping panels, each comprising two parents and more than 100 progeny. Chi-square goodness-of-fit test (chi(2)) revealed that only 19 microsatellite and 28 AFLP markers showed a highly significant segregation distortion (P < 0.005). Linkage analysis with a LOD score of 4.5 revealed 43 and 46 linkage groups in male and female linkage maps respectively. The male map consisted of 176 microsatellite and 49 AFLP markers spaced every approximately 11.2 cM, with an observed genome length of 2033.4 cM. The female map consisted of 171 microsatellite and 36 AFLP markers spaced every approximately 13.8 cM, with an observed genome length of 2182 cM. Both maps shared 136 microsatellite markers, and the alignment between them indicated 38 homologous pairs of linkage groups including the linkage group representing the sex chromosome. The karyotype of P. monodon is also presented. The tentative assignment of the 44 pairs of P. monodon haploid chromosomes showed the composition of forty metacentric, one submetacentric and three acrocentric chromosomes. Our maps provided a solid foundation for gene and QTL mapping in the tiger shrimp.

Microsatellite and mitochondrial haplotype diversity reveals population differentiation in the tiger shrimp (Penaeus monodon) in the Indo-Pacific region.

The black tiger shrimp (Penaeus monodon) is an ecologically and economically important penaeid species and is widely distributed in the Indo-Pacific region. Here we investigated the genetic diversity of P. monodon (n = 355) from eight geographical regions by genotyping at 10 microsatellite loci. The average observed heterozygosity at various loci ranged from 0.638 to 0.743, indicating a high level of genetic variability in this region. Significant departures from Hardy-Weinberg equilibrium caused by heterozygote deficiency were recorded for most loci and populations. Pairwise F(ST) and R(ST) values revealed genetic differentiation among the populations. Evidence from the assignment test showed that the populations in the West Indian Ocean were unique, whereas other populations examined were partially admixed. In addition, the non-metric multidimensional scaling analysis indicated the presence of three geographic groups in the Indo-Pacific region, i.e. the African populations, a population from western Thailand and the remaining populations as a whole. We also sequenced and analysed the mitochondrial control region (mtCR) in these shrimp stocks to determine whether the nuclear and mitochondrial genomes show a similar pattern of genetic differentiation. A total of 262 haplotypes were identified, and nucleotide divergence among haplotypes ranged from 0.2% to 16.3%. Haplotype diversity was high in all populations, with a range from 0.969 to 1. Phylogenetic analysis using the mtCR data revealed that the West Indian Ocean populations were genetically differentiated from the West Pacific populations, consistent with the microsatellite data. These results should have implications for aquaculture management and conservation of aquatic diversity.

Performance of WSSV-infected and WSSV-negative Penaeus monodon postlarvae in culture ponds.

In a survey of 27 Penaeus monodon culture ponds stocked with postlarvae (approximately PL10) at medium density (approximately 40 shrimp m(-2)), single-step nested white spot syndrome virus (WSSV) PCR was used to measure the WSSV infection rates in the shrimp populations within 1 mo after stocking. Seven ponds were initially WSSV-free, and the shrimp in 5 of these were harvested successfully. In the ponds (n = 6) where detection rates were higher than 50%, mass mortality occurred during the growth period, and none of these ponds was harvested successfully. In a subsequent study, P. monodon brooders were classified into 3 groups according to their WSSV infection status before and after spawning: brooders that were WSSV-positive before spawning were assigned to group A; spawners that became WSSV-positive only after spawning were assigned to group B; and group C consisted of brooders that were still WSSV-negative after spawning. WSSV screening showed that 75, 44 and 14%, respectively, of group A, B and C brooders produced nauplii that were WSSV-positive. Most (57%; 16/28) of the brooders in group A produced nauplii in which the WSSV prevalence was high (>50%). When a pond was stocked with high-prevalence nauplii from 1 of these group A brooders, an outbreak of white spot syndrome occurred within 3 wk and only approximately 20% of the initial population survived through to harvest (after 174 d). By contrast, 2 other ponds stocked with low-prevalence and WSSV-negative nauplii (derived respectively from 2 brooders in group B), both had much higher survival rates (70 to 80%) and yielded much larger (approximately 3x by weight) total harvests. We conclude that testing the nauplii is an effective and practical screening strategy for commercially cultured P. monodon.

Regional variations in the apparent diffusion coefficient and the intracellular distribution of water in rat brain during acute focal ischemia.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient of water (ADC) rapidly drops in ischemic tissue after cerebral artery occlusion. This acute drop is thought to be caused by the loss of extracellular fluid and the gain of intracellular fluid. To test the latter possibility, changes in ADC and the size of several cellular compartments were assessed in 3 regions of rat brain at the end of 90 minutes of focal cerebral ischemia. METHODS: One middle cerebral artery was permanently occluded in 8 Sprague-Dawley rats; sham occlusions were performed in 2 other rats. ADC maps were generated 90 minutes later, and the brains were immediately perfusion fixed. Three regions of interest (ROIs) were defined on the basis of ADC range. Various neuronal, astrocytic, and capillary compartments in each ROI were quantified with light and electron microscopy. RESULTS: At the end of 90 minutes of ischemia, mean ADC was normal in the cortex of sham-operated rats and the contralateral cortex of ischemic rats (ROI-a), 25% lower in the ipsilateral frontoparietal cortex (ROI-b), and 45% lower in the ischemic lateral caudoputamen (ROI-c). At this time, the frequency of swollen astrocytic cell bodies and volume of swollen dendrites and astrocytic processes in neuropil were ROI-a

[A preliminary analysis on a group of low molecular weight RNases in wheat and related species].

By employing RNase activity gel analysis, we detected a novel group of RNases in wheat and related species. The molecular weight of the RNases varied from 8-14 kDa, which was lower than that of most plant RNases characterized previously. The small RNases expressed abundantly in seedlings and differed in their optimal pH and ionic requirement in digesting RNA substrate. Several members of the small RNases were detected in dormant and germinating wheat seeds. During germination, the activity of two RNases did not change significantly whereas that of the other two RNases showed a gradual pattern of decrease and increase, respectively.

Secondary decline in apparent diffusion coefficient and neurological outcomes after a short period of focal brain ischemia in rats.

This study was designed to characterize the initial and secondary changes of the apparent diffusion coefficient (ADC) of water with high temporal resolution measurements of ADC values and to correlate ADC changes with functional outcomes. Fourteen rats underwent 30 minutes of temporary middle cerebral artery occlusion (MCAO). Diffusion-, perfusion-, and T2-weighted imaging was performed during MCAO and every 30 minutes for a total of 12 hours after reperfusion (n = 6). Neurological outcomes were evaluated during MCAO, every 30 minutes for a total of 6 hours and at 24 hours after reperfusion (n = 8). The decreased cerebral blood flow during MCAO returned to normal after reperfusion and remained unchanged thereafter. The decreased ADC values during occlusion completely recovered at 1 hour after reperfusion. The renormalized ADC values started to decrease secondarily at 2.5 hours, accompanied by a delayed increase in T2 values. The ADC-defined secondary lesion grew over time and was 52% of the ADC-defined initial lesion at 12 hours. Histological evaluation demonstrated neuronal damage in the regions of secondary ADC decline. Complete resolution of neurological deficits was seen in 1 rat at 1 hour and in 6 rats between 2.5 and 6 hours after reperfusion; no secondary neurological deficits were observed at 24 hours. These data suggest that (1) a secondary ADC reduction occurs as early as 2.5 hours after reperfusion, evolves in a slow fashion, and is associated with neuronal injury; and (2) renormalization and secondary decline in ADC are not associated with neurological recovery and worsening, respectively.

Transient and permanent resolution of ischemic lesions on diffusion-weighted imaging after brief periods of focal ischemia in rats : correlation with histopathology.

BACKGROUND AND PURPOSE: The early ischemic lesions demonstrated by diffusion-weighted imaging (DWI) are potentially reversible. The purposes of this study were to determine whether resolution of initial DWI lesions is transient or permanent after different brief periods of focal brain ischemia and to evaluate histological outcomes. METHODS: Sixteen rats were subjected to 10 minutes (n=7) or 30 minutes (n=7) of temporary middle cerebral artery occlusion or sham operation (n=2). DWI, perfusion-weighted imaging (PWI), and T(2)-weighted imaging (T(2)WI) were performed during occlusion; immediately after reperfusion; and at 0.5, 1.0, 1.5, 12, 24, 48, and 72 hours after reperfusion. After the last MRI study, the brains were fixed, sectioned, stained with hematoxylin and eosin, and evaluated for neuronal necrosis. RESULTS: No MRI or histological abnormalities were observed in the sham-operated rats. In both the 10-minute and 30-minute groups, the perfusion deficits and DWI hyperintensities that occurred during occlusion disappeared shortly after reperfusion. The DWI, PWI, and T(2)WI results remained normal thereafter in the 10-minute group, whereas secondary DWI hyperintensity and T(2)WI abnormalities developed at the 12-hour observation point in the 30-minute group. Histological examinations demonstrated neuronal necrosis in both groups, but the number of necrotic neurons was significantly higher in the 30-minute group (95+/-4%) than in the 10-minute group (17+/-10%, P<0.0001). CONCLUSIONS: Transient or permanent resolution of initial DWI lesions depends on the duration of ischemia. Transient resolution of DWI lesions is associated with widespread neuronal necrosis; moreover, permanent resolution of DWI lesions does not necessarily indicate complete salvage of brain tissue from ischemic injury.

Reversal of acute apparent diffusion coefficient abnormalities and delayed neuronal death following transient focal cerebral ischemia in rats.

Twenty-two rats were subjected to 8, 15, 30, or 60 minutes of temporary middle cerebral artery occlusion (n = 5 per group) or sham occlusion (n = 2) in the magnetic resonance imaging unit. Diffusion-, perfusion-, and T2-weighted imaging were acquired before and during occlusion, and after reperfusion. A coregistration method was used to correlate the acute changes of the average apparent diffusion coefficient (ADCav) with the histology after 72 hours at the same topographic sites. The initially reduced ADCav values recovered completely in both the lateral caudoputamen and upper frontoparietal cortex in the 8-, 15-, and 30-minute groups, partially in the cortex, and not at all in the caudoputamen in the 60-minute group. The histology showed that the caudoputamen was either normal or had mild neuronal injury in the 8-minute group and invariably had some degree of neuronal death in the 15-, 30-, and 60-minute groups, whereas the cortex was either normal or had varying degrees of neuronal injury in all groups. No histological abnormalities were seen in the sham-operated rats. Our data suggest that acute ADCav reversal does not always predict tissue recovery from ischemic injury and that temporary focal ischemia for even 8-minute duration can cause delayed neuronal death that is more severe in the caudoputamen where the initial ADCav decline was greater than in the cortex.

Studies on effective PCR screening strategies for white spot syndrome virus (WSSV) detection in Penaeus monodon brooders.

We re-tested stored (frozen) DNA samples in 5 independent polymerase chain reaction (PCR) replicates and confirmed that equivocal test results from a previous study on white spot syndrome virus (WSSV) in brooders and their offspring arose because amounts of WSSV DNA in the test samples were near the sensitivity limits of the detection method. Since spawning stress may trigger WSSV replication, we also captured a fresh batch of 45 brooders for WSSV PCR testing before and after spawning. Replicates of their spawned egg batches were also WSSV PCR tested. For these 45 brooders, WSSV prevalence before spawning was 67% (15/45 1-step PCR positive, 15/45 2-step PCR positive and 15/45 2-step PCR negative). Only 27 (60%) spawned successfully. Of the successful spawners, 56% were WSSV PCR positive before spawning and 74% after. Brooders (15) that were heavily infected (i.e. 1-step PCR positive) when captured mostly died within 1 to 4 d, but 3 (20%) did manage to spawn. All their egg batch sub-samples were 1-step PCR positive and many failed to hatch. The remaining 30 shrimp were divided into a lightly infected group (21) and a 2-step PCR negative group (9) based on replicate PCR tests. The spawning rates for these 2 groups were high (81 and 78%, respectively). None of the negative spawners (7) became WSSV positive after spawning and none gave egg samples positive for WSSV. In the lightly infected group (21), 6 brooders were 2-step WSSV PCR negative and 15 were 2-step WSSV PCR positive upon capture. However, all of them were WSSV PCR positive in replicate tests and after spawning or death. Four died without spawning. The remaining 17 spawned but only 2 gave egg samples PCR negative for WSSV. The other 15 gave PCR positive egg samples, but they could be divided into 2 spawner groups: those (7) that became heavily infected (i.e. 1-step PCR positive) after spawning and those (8) that remained lightly infected (i.e. became or remained 2-step PCR positive only). Of the brooders that became heavily infected after spawning, almost all egg sample replicates (91 %) tested 2-step PCR positive. One brooder even gave heavily infected (i.e. 1-step PCR positive) egg samples. For the brooders that remained lightly infected after spawning, only 27% of the egg sample replicates were 2-step PCR positive. Based on these results, we recommend that to avoid false negatives in WSSV PCR brooder tests screening tests should be delayed until after spawning. We also recommend, with our PCR detection system, discarding all egg batches from brooders that are 1-step PCR positive after spawning. On the other hand, it may be possible with appropriate monitoring to use eggs from 2-step PCR positive brooders for production of WSSV-free or lightly infected postlarvae. These may be used to stock shrimp ponds under low-stress rearing conditions.

Incomplete infarct and delayed neuronal death after transient middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: The clinical syndrome of transient ischemic attacks is accompanied in a significant percentage of patients by brain lesions or neuroimaging abnormalities whose structural counterparts have not been defined. The objective of this study was to analyze, in an experimental model of short-term (< 25 minutes) focal ischemia and long-term (< or = 28 days) reperfusion, the extent and nature of the structural abnormalities affecting neurons and glia located within the territory of the transiently occluded artery. METHODS: Adult Wistar rats (n = 121) had the origin of one middle cerebral artery (MCA) occluded with a nylon monofilament for periods of 10 to 25 minutes. Experiments of transient MCA occlusion were terminated at variable periods ranging from 1 day to 4 weeks. Control experiments consisted of (1) MCA occlusion without reperfusion (n = 7) lasting 7 to 14 days and (2) sham operations (n = 2) followed by 1- to 4-day survival. After in situ fixation, brain specimens were serially sectioned and subjected to detailed morphometric evaluations utilizing light and electron microscopes. The statistical method used to evaluate the results was based on ANOVA followed by Bonferroni's corrected t test and Student's t test comparisons. RESULTS: Brain lesions were not detectable in the sham-operated controls. All brains with permanent MCA occlusion (7 to 14 days) had large infarctions with abundant macrophage infiltration and early cavitation. Forty-five (37%) of the experiments involving transient MCA occlusion had no detectable brain lesions after 4 weeks. Selective neuronal necrosis was found in 76 of 121 rats (63%) with transient MCA occlusion. Neuronal necrosis always involved the striatum, and in 29% of the brains with ischemic injury, necrosis also included a short segment of the cortex. In the striatum, the length of the arterial occlusion was the main determinant of the number of necrotic neurons (20 minutes [22.6 +/- 19] is worse than 10 minutes [4.9 +/- 7]) (P < .0001). In the cortex, the length of reperfusion determined the number of necrotic neurons appearing in layer 3. Experiments with reperfusion of 4 to 7 days' duration yielded more necrotic neurons per microscopic field (2.02 +/- 3) than those lasting fewer days (0.04 +/- 0.1) (P < .05). The histological features of these lesions underwent continuous change until the end of the fourth week, at which time necrotic neurons were still visible both in the striatum and in the cortex. CONCLUSIONS: Arterial occlusions of short duration (< 25 minutes) produced, in 76 of 121 experiments (63%), brain lesions characterized by selective neuronal necrosis and various glial responses (or incomplete infarction). This lesion is entirely different from the pannecrosis/cavitation typical of an infarction that appears 3 to 4 days after a prolonged arterial occlusion. Delayed neuronal necrosis, secondary to a transient arterial occlusion or increasing numbers of necrotic neurons in experiments with variable periods of reperfusion, was a response observed only at a predictable segment of the frontoparietal cortex.

DNA scission after focal brain ischemia. Temporal differences in two species.

BACKGROUND AND PURPOSE: Species- and model-dependent differences in cell response to focal brain ischemia may underlie differences in adhesion receptor expression. The aim of this study was to quantitatively evaluate the spatial and temporal distribution of dUTP incorporation into damaged DNA, as an indicator of ischemic injury, in the corpus striatum. METHODS: Cerebral ischemia was produced in 16 nonhuman primates and 19 rats by occluding the middle cerebral artery (MCA:O) with reperfusion for various periods. In situ dUTP was incorporated into cells with DNA damage by terminal deoxynucleotidyl transferase (TdT), DNA polymerase I, or the Klenow fragment of DNA polymerase. Dual immunolabeling experiments with immunoprobes against neuronal, vascular, or glial marker proteins were performed. RESULTS: Significant topographical differences in dUTP between the two species were seen. In both models the TdT and polymerase I regions changed characteristically during focal ischemia. The number and density of dUTP-labeled cells increased with time from MCA:O and were dramatically different between the species (2P < .001). By 2 hours of ischemia, the density of dUTP label was 48.8 +/- 10.3 cells/mm2 in the primate and 2.4 +/- 0.8 cells/mm2 in the rat (2P < .05), but these values became nearly identical by 24 hours of reperfusion. In the primate, 80.0 +/- 6.6% of labeled cells displayed microtubule-associated protein-2 antigen (at 2-hour MCA:O), while 1.8 +/- 0.5% were associated with microvessels at 24 hours of reperfusion. CONCLUSIONS: In situ detection of DNA damage, accomplished by three methods, reveals distinct temporal, topographical, and density differences in ischemic injury to cells in the primate and the rat corpus striatum as a result of MCA:O.

Severe transient hypoglycemia causes reversible change in the apparent diffusion coefficient of water.

BACKGROUND AND PURPOSE: The aim of this study was to determine the effects of temporary severe hypoglycemia on the apparent diffusion coefficient (ADC) acquired by diffusion-weighted MRI of brain water with the use of serial multislice ADC mapping in rats. Severe hypoglycemia reduces the extracellular space volume, as does ischemia. Demonstrating a reduction of ADC with hypoglycemia should increase our understanding of the mechanisms underlying ADC changes in ischemia and other conditions. METHODS: Fasted rats were given regular insulin (15 IU/kg IP). Rats were subjected to 15 minutes (n = 5) and 50 minutes (n = 5) of temporary severe hypoglycemia, causing a transiently isoelectric electroencephalogram (EEG). ADC mapping was performed every 30 seconds beginning at the onset of isoelectricity for 8.5 minutes. ADC maps were also obtained later during the isoelectric EEG period and 10, 20, 30, and 40 minutes after glucose infusion. Control images were obtained from a separate group of animals suffering cardiac arrest (n = 5). RESULTS: Abnormal ADC values were not observed before the onset of cerebral isoelectricity, except for isolated areas in the cortex and periventricular regions. Cortical ADC values globally declined at the onset of EEG isoelectricity. The ADC decline spread to subcortical regions within a few minutes. During the isoelectric period, significant declines of ADC values (27% to 45%) occurred in the entire brain. Glucose infusion normalized most of the ADC changes, even after a 50-minute period of isoelectricity. CONCLUSIONS: ADC mapping during hypoglycemia clearly demonstrates changes likely related to energy depletion. Most of these ADC declines were reversible. Hypoglycemia is a condition known to be associated with shrinkage of the extracellular space. These observations support the hypothesis that ADC reductions observed in ischemia are also related to shifts of water from the extracellular to the intracellular compartment.