Tobacco Use: A Major Risk Factor of Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (sICH) is one of the deadliest subtypes of stroke, and no treatment is currently available. One of the major risk factors is tobacco use. In this article, we review literature on how tobacco use affects the risk of sICH and also summarize the known effects of tobacco use on outcomes following sICH. Several studies demonstrate that the risk of sICH is higher in current cigarette smokers compared to non-smokers. The literature also establishes that cigarette smoking not only increases the risk of sICH but also increases hematoma growth, results in worse outcomes, and increases the risk of death from sICH. This review also discusses potential mechanisms activated by tobacco use which result in an increase in risk and severity of sICH. Exploring the underlying mechanisms may help alleviate the risk of sICH in tobacco users as well as may help better manage tobacco user sICH patients

Ischemic brain injury in diabetes and endoplasmic reticulum stress

Diabetes is a widespread disease characterized by high blood glucose levels due to abnormal insulin activity, production, or both. Chronic diabetes causes many secondary complications including cardiovascular disease: a life-threatening complication. Cerebral ischemia-related mortality, morbidity, and the extent of brain injury are high in diabetes. However, the mechanism of increase in ischemic brain injury during diabetes is not well understood. Multiple mechanisms mediate diabetic hyperglycemia and hypoglycemia-induced increase in ischemic brain injury. Endoplasmic reticulum (ER) stress mediates both brain injury as well as brain protection after ischemia-reperfusion injury. The pathways of ER stress are modulated during diabetes. Free radical generation and mitochondrial dysfunction, two of the prominent mechanisms that mediate diabetic increase in ischemic brain injury, are known to stimulate the pathways of ER stress. Increased ischemic brain injury in diabetes is accompanied by a further increase in the activation of ER stress. As there are many metabolic changes associated with diabetes, differential activation of the pathways of ER stress may mediate pronounced ischemic brain injury in subjects suffering from diabetes. We presently discuss the literature on the significance of ER stress in mediating increased ischemia-reperfusion injury in diabetes. [Display omitted] •The mechanism of increased ischemic brain injury in diabetes is not well understood.•Endoplasmic reticulum (ER) stress is an important mechanism of ischemic brain injury.•The pathways of ER stress are modulated during diabetes.•Diabetic increase in ischemic injury occurs along with enhanced ER stress activation.•ER stress activation may mediate pronounced ischemic brain injury in diabetes

Factors influencing nutritional practices among mothers in Dakar, Senegal.

BACKGROUND:Maternal undernutrition is a leading cause of maternal mortality. Furthermore, health statuses and habits of mothers influence health statuses of newborns as well as healthy habits and mortality of children. The Senegal government is aware of the severity of these issues and has devised a national policy goal of reducing maternal, infant, and adolescent mortality rates by the end of 2018. This study aimed to identify nutritional knowledge, attitudes, and practices of lactating women in Senegal, and determine factors related to nutritional practices to obtain basic data for developing a maternal and child nutrition project. METHOD:This study used a mixed-method approach, collecting data via structured questionnaires administered to lactating women in Senegal and semistructured interviews with seven stake-holders. Questions for stuctured questionnaires were about nutritional knowledge, attitudes, and practices. For the quantitative analysis of the structured questionnaires, data from 171 participants analyzed using independent t-tests, Pearson's correlation coefficients, and multiple linear regression analysis. Interview data were analyzed using an inductive thematic analysis approach. The questions for the interviews concerned maternal and child nutritional status, causes of undernutrition, and restrictions. RESULTS:Factors significantly related to healthy nutritional practices(explaining 27.1% of variance) included having a household (B = 1.03, p = .015) and a mother (B = 0.96, p = .017) with an above primary school education, and being in the 5th quintile of income level (B = 1.24, p = .014). The interviews with seven stakeholders revealed obstructive factors of nutritional management were insufficient nutritional programs within health centers, incomplete national policy on nutrition, lack of general interest in undernutrition-related topics, inadequate economic environment, and the absence of partnerships to produce sustainable solutions. CONCLUSION:Education and income levels, rather than knowledge and attitudes, had a strong relationship with healthy nutritional practices. Therefore, economic factors and educational background must be considered to succeed in Senegalese nutrition projects

Abstract TMP117: Exposure to Single or Recurrent Hypoglycemia Increases Stroke Risk in Insulin-Treated Female Diabetic Rats

Abstract only Stroke is a serious complication of diabetes. Intensive treatment of diabetes increases the risk of recurrent hypoglycemia (RH). Hypoglycemia exposure causes prothrombotic effects. Earlier, we demonstrated that exposure to single hypoglycemia (SH), 5-day RH (once every day), and twice-a-week RH for 6 weeks increases stroke risk in male insulin-treated diabetic (ITD) rats. In the present study, we determined the effect of SH and RH on stroke risk/thrombosis in female rats. Streptozotocin diabetic female rats were treated for hyperglycemia using insulin pellets (Figure A). Rats were randomly assigned to either hyperinsulinemic euglycemia (ITD+RH+Glucose, control) or hyperinsulinemic hypoglycemia (ITD+RH) groups (3 h duration) (Figure B). Separate groups tested the effect of SH, RH for 5 days, or RH for 6 weeks. Based on the results of the male studies, stroke risk after SH, 5-day RH, and 6-week RH were assessed on days 1, 7, and 3 post-last hypoglycemia, respectively. Groups were balanced (confirmed by Chi square test) in terms of the proportion of animals at different stages of the estrous cycle. To assess the risk of stroke, the carotid artery and jugular vein were linked with a shunt containing a suture, and the weight of the clot accumulated on the suture following 15 min of blood flow was quantified as a measure of stroke risk/thrombosis. The clot weight in the SH-exposed ITD group was significantly higher by 47% (22±3 mg, n=9, p<0.05) when compared to its respective control (15±1 mg, n=8). The clot weight determined 7 days after the 5-day ITD+RH group (18±1 mg, n=7) was significantly (p<0.05) higher than its control group (15±1 mg, n=9). The clot weight in the 6-week ITD+RH group was significantly higher by 47% (20±2 mg, n=9, p<0.01) when compared to its control (14±1 mg, n=7) (Figure C). Our results show that similar to male rats, SH and RH increase stroke risk in female ITD rats. We are currently evaluating the underlying mechanisms. Acknowledgment: NIH (NS122808)

Functional Heterogeneity of Red Cell-Derived Microparticles from Different Sources: Calcium Ionophore Vs. Storage Vs. Extrusion

Abstract BACKGROUND. Cell derived microparticles (MP), are small vesicle (<1um) released in cell activation or apoptosis. Depending on stimulus, MPs can be heterogeneous in phenotype and functional activities such as hemostatic vs thrombogenic vs proinflammatory. In this study, we compared RMP produced in three ways: (1) induced by calcium ionophore (RMP-CaI), (2) released from packed cells (PC) during storage up to 42 days (RMP-Stor) and (3)by high-pressure extrusion of washed RBC (RMP-HPE). The aim of the study was to elucidate how the functional property of these species vary with mode of production. METHODS. For RMP-Stor, samples were taken at intervals up to 42 days of PC stored at 4oC, then centrifuged to recover the RMP released. For RMP-CaI, supernatants of fresh RBC exposed to Ca2+/ionophore (A23187) for 30 min were centrifuged. For RMP-HPE, washed RBC were subjected to high-pressure extrusion, and the resulting RMP were collected by centrifugation and washed. Flow cytometric counts were by CD235a (glycophorin A) and annexinV (AnV) binding. Thromboelastography (TEG) compared equal counts of each sample type, based on CD235a, diluted as needed with particle-free pooled plasma (PFP). RESULTS: (1) Yield per mL of initial packed RBC: The highest yield of RMP was seen in RMP-HPE, as expected since ≈100% of RBC convert to RMP-HPE. This was followed by RMP-CaI, which was about 3x more than RMP-Stor at 42 days. The RMP-Stor increased linearly from day 21 to 42. (2) AnV binding was expressed as ratio AnV+/CD235+, and is a marker of procoagulant phospholipid. This ratio was least in RMP-HPE (0.38) and more than doubled in both RMP-Stor (0.92) and RMP-CaI (1.0). (3) Size of RMP by forward scatter (FS) increased steadily with time in RMP-Stor, from day 21 (0.56 um) to day 42 (0.79 um). These values are somewhat larger than RMP-CaI (0.47 um) or RMP-HPE (0.52 um). The side-scatter signal correlated with the FS values. (4) Acetylcholinesterase (AChE) activity was by far highest in RMP-Stor (56 nM/min, per 106 particles) vs. 4.5 for RMP-CaI, and 1.5 for RMP-HPE. (5) Procoagulant activity: In TEG, the increase in MA (maximum amplitude) by addition of RMP-Stor was 64 mm, but was not increased by RMP-HPE or RMP-CaI. The R-time (lag) showed greatest shortening with RMP-Stor (10.2 min), followed by RMP-CaI (6.7 min), and RMP-HPE (3.6 min) (6)Anti-fibrinolytic activity: In presence of 0.4 ug/mL of tissue plasminogen activator (tPA), for the purpose of making fibrinolytic activity more detectable in a short time, all 3 species of RMP effectively inhibit t-PA-mediated fibrinolysis measured by TEG parameters, including MA, Ly30, and TTG (total thrombus formation). The RMP-HPE was most effective followed by RMP-Stor, and RMP-CaI. CONCLUSION/DISCUSSION. Results demonstrate clear and distinctive differences in functional and phenotypic properties of the 3 species compared. RMP-Stor and RMP-CaI are lager in size, higher in PS and AChE expression, and higher in procoagulant activity, compared to RMP-HPE. On the other hand, RMP-HPE are higher in number generated per mL packed RBC and exhibit stronger inhibition of tPA-mediated fibrinolysis. It is well known that RMP generated by storage and calcium ionophore are enriched in lipid rafts. In contrast, the RMP-HPE are not enriched in lipid rafts, as reflected in low AChE. We conjecture that the contents of lipid raft on RMP may play an important role in determining the functional properties of RMP. Disclosures No relevant conflicts of interest to declare

Synthesis and side-chain engineering of phenylnaphthalenediimide (PNDI)-based n-type polymers for efficient all-polymer solar cells

We designed and synthesized a series of n-type conjugated polymers by introducing phenylnaphthalenediimide (PNDI) as a novel n-type building block, and investigated the effect of side-chain engineering of the polymer acceptors on the performance of all-polymer solar cells (all-PSCs). The optical, electrochemical, and structural properties of the polymers with three different side chains of 2-ethylhexyl (PPNDI-EH), 2-butyloctyl (PPNDI-BO), and 2-hexyldecyl (PPNDI-HD) groups were examined. Interestingly, the PNDI-based polymer having the longest side chain showed a higher degree of edge-on oriented intermolecular assembly in thin films, thereby resulting in the highest field-effect electron mobility among the three polymers. Also, we examined the performance of PNDI-based polymers as polymer acceptors in all-PSCs. Unlike the trend in the field-effect transistor, the PPNDI-BO-based all-PSCs exhibited the highest power conversion efficiency (PCE) of 4.25% among the three polymer blends. This was attributed to the well-balanced hole/electron transport and higher exciton dissociation probability in the PPNDI-BO-based all-PSCs, benefitted from the well-intermixed blend morphology between the polymer donor and PPNDI-BO

Automated Assessment of Hematoma Volume of Rodents Subjected to Experimental Intracerebral Hemorrhagic Stroke by Bayes Segmentation Approach

Simulating a clinical condition of intracerebral hemorrhage (ICH) in animals is key to research on the development and testing of diagnostic or treatment strategies for this high mortality disease. In order to study the mechanism, pathology, and treatment for hemorrhagic stroke, various animal models have been developed. Measurement of hematoma volume is an important assessment parameter to evaluate post-ICH outcomes. However, due to tissue preservation conditions and variables in digitization, quantification of hematoma volume is usually labor intensive and sometimes even subjective. The objective of this study is to develop an automated method that can accurately and efficiently obtain unbiased cerebral hematoma volume. We developed an application (MatLab program) that can delineate the brain slice from the background and use the Hue information in the Hue/Saturation/Value (HSV) color space to segment the hematoma region. The segmentation threshold of Hue is calculated based on the Bayes classifier theorem so that the minimum error is mathematically ensured and automated processing is enabled. To validate the developed method, we compared the outcomes from the developed method with the hemoglobin content by the spectrophotometric assay method. The results were linearly correlated with statistical significance. The method was also validated by digital phantoms with an error less than 5% compared with the ground truth from the phantoms. Hematoma volumes yielded by the automated processing and those obtained by the operator’s manual operation are highly correlated. This automated segmentation approach can be potentially used to quantify hemorrhagic outcomes in rodent stroke models in an unbiased and efficient way

Abstract TP129: Increased Levels Of Matrix Metalloproteinases-induced BBB Dysfunction May Be Responsible For Increased Post-sich Hematoma Growth In Nicotine-exposed Rats

Byline: Priyanka Khushal, Univ of Miami, Miami, FL; Sunjoo Cho, Miami, FL; Ashish K Rehni, UNIVERSITY OF MIAMI MILLER SCHOOL O, Miami, FL; Ami P Raval, UNIVERSITY OF MIAMI, Miami, FL; Miguel A Perez-Pinzon, UNIVERSITY MIAMI MILLER SCH. OF MED, Miami, FL; Kunjan R Dave, Univ of Miami, Miami, FL Spontaneous intracerebral hemorrhage (sICH) is the deadliest type of stroke, accounting for as high as 28% of all strokes. Tobacco use is one of the major risk factors of sICH, and it also worsens outcomes following sICH. In our earlier study, we observed that nicotine exposure increases TNFð levels in brain vessels, impairs BBB integrity, and increases post-sICH hematoma volume in a TNFð-dependent manner compared to saline-exposed controls. Earlier studies have demonstrated interactions between MMPs and TNFð. Increased levels of matrix metalloproteinases (MMPs) have been found in sICH patients and nicotine-exposed individuals. MMPs are involved in BBB breakdown, edema formation, hematoma expansion, and neuronal loss that follow hematoma development after sICH. In the present study, we tested the hypothesis that nicotine exposure-induced increase in TNFð is responsible for increased post-sICH hematoma volume in a MMP-dependent manner. To test our hypothesis, young male and female rats were exposed to chronic nicotine treatment for 2-3 weeks using osmotic pumps containing either saline or nicotine (4.5 mg/kg/day). Levels of MMPs (2, 3, 9, and 12) and GAPDH were evaluated in brain homogenates using Western blot. Nicotine-treated female rats showed a 37% (100Ø7 vs. 137Ø10, p<0.05), 144% (100Ø18 vs. 244Ø16, p<0.01), 29% (100Ø7 vs. 129Ø9, p<0.05), 22% (100Ø6 vs. 122Ø6, p<0.05), and 24% (100Ø6 vs. 124Ø7, p<0.05) increase in levels of pro and cleaved forms of MMP-3, cleaved form of MMP-9, pro and cleaved forms of MMP-12, respectively, compared to saline-treated female rats. We are in the process of evaluating levels of MMPs in male samples. Considering the role of MMP-9 in BBB integrity, using both TNFð and MMP-9 inhibitors, we are also in the process of evaluating if TNFð increases post-sICH hematoma growth in nicotine-exposed rats via increased levels of MMP-9. The results so far imply that increased TNFð levels in nicotine-exposed rats may be responsible for increased post-sICH hematoma growth in a MMP-dependent manner. Support: James Esther King Biomedical Research Grant 9JK08 and PK is a recipient of the Lois Pope Neuroscience Summer Research Fellowship.Academi