Glucose uptake and stroke survival

Dr. Ritter,

I was wondering if a factor in the high mortality rates of diabetic stroke victim could have to do with poor uptake of glucose to leukocytes and other cells, which would aid in recovery.  As we know, these cells require glucose as a source of energy, and poor cellular glucose uptake is a major problem of diabetes (especially type II).  With a decreased amount of energy it seems the cells involved in the mending processes would be greatly hindered.  Is there any research looking in to this or am I just completely mistaken?

The Importance of Stroke Awareness

What is a stroke and how does it occur?

A stroke occurs when a portion of the brain dies due to a lack of oxygen. Usually an artery that supplies the brain with oxygen carrying blood has been damaged or blocked by a clot (Ischemic Stroke); this is how most strokes occur. The other, small percentage, happens when an artery in the brain bursts (Hemorrhagic Stroke).

In an Ischemic stroke a blood clot or fatty deposits on a vessel wall, are formed in the heart or neck and are moved/swept upwards to the brain where it then blocks an artery. Protective mechanisms of the brain immediately begin to fight back by raising the blood pressure in hopes of clearing the artery. In the meantime, cells around the brain are beginning to shut down due to a lack of oxygenated blood. This occurs in 85% of strokes.

With a Hemorrhagic stroke, the problem is a little more disastrous. In this case, an artery is ruptured, preventing normal flow of blood and allowing it to leak into the brain tissue. This causes the brain to swell. If the swelling is continuous, the skull can crush the centers for consciousness and breathing. 13% of strokes are hemorrhagic.

Symptoms or Warning signs of a stroke

A simple acronym used to determine if someone, or yourself, is having a stroke is called FAST. Facial weakness: ask the individual to smile. If one side of their face seems to droop, then it is one of the beginning onsets of a stroke. The next step is Arm and leg weakness. Ask him or her to then raise both arms. If they have trouble bringing one of their arms up, it is another symptom. Speech problems is the next big one. Ask the person to repeat a simple sentence that, in any other circumstances, they would have no problem completing. For example, "It's a cloudy day." The last step in FAST is Timing. Timing is critical: TIME IS BRAIN. There is only a small window of time that the most effective treatment for a stroke can be administered; three hours of the onset of stroke. The drug administered is tPA, a de-clotting agent. However, there is a concern with tPA. In 6% of cases, tPA causes bleeding in the brain and can be fatal. This is dangerous, especially if it was found that the patient had not even had a stroke. There is no easy way to determine if someone is having a stroke. The best way is thorugh an M.R.I and the confirmation of a neurologist. But since both are unlikely to be found on hand, the responsibility lies with the emergency room doctor.

Risk Factors: The controllable and the out of hand

Stroke risk factors that are uncontrollable have to do with increasing age, male sex, race (especially African Americans), and family history of stroke. There are, however, factors that can be modified through medical treatment and lifestyle changes. These include high blood pressure, cigarette smoking, diabetes, obesity, Aspirin, high blood cholesterol (a leading factor in stroke), and heart disease. You can also reduce your risk by conducting annual physicals with your physician, keeping a healthy diet, being aware of your family history, and maintaining a healthy weight.

**If your interested in learning more about stroke, I found a pretty awesome video link. It won't take up much of your time and your not obligated to watch it :)

Crucial Facts about Stroke Video:

http://video.on.nytimes.com/?fr_story=1597c973a409a01c13d05376ef6312ad307251c1


References:

American Stroke Foundation- http://www.americanstroke.org

The Stroke Awareness Foundation- http://www.strokeinfo.org/

Stroke and Inflammation: delayed mechanism of tissue damage

We now know that stroke-induced damage often takes place long after the initial ischemic event has subsided. I thought a brief overview of some potential mechanisms accounting for this delayed onset damage would be interesting and helpful in understanding this complex process.


Until relatively recently all tissue damage associated with an infarct was presumed to have occurred within the first few hours following the event. After this time, all structural deficits were thought to be fixed, leading to few treatments targeted specifically at mechanisms of delayed damage. More recently, however, it has been shown that delayed mechanisms of damage can significantly increase the degree of tissue damage caused by acute, transient strokes.

Through the use of modern neuroimaging methods, it has been shown that there can be significant growth of the infarct for more that 24 hours after the initial event. Also, other neural damage resulting from the initial stroke has an even longer timeline. These recent elucidations clearly point out the need to better understand delayed mechanisms of damage and provide new brain protective strategies.

One key player, linked to delayed damage associated with acute stroke, is inflammation. Listed are a few of the central arguments for implicating inflammation in the delayed damage mechanism:

1.) Inflammatory cells can be found in the brain after stroke.
2.) Anti-inflammatory strategies can protect against experimental stroke.
3.) Disruption of genes linked to inflammation (iNOS, from posted review article) can protect against stroke.
4.) Inducing brain inflammation causes neural tissue damage.

The stroke-induced inflammatory response is a complex process usually taking place after blood flow has been restored. Reperfusion of the ischemic cells with oxygenated blood (either spontaneous or by means of TPA) induces formation of reactive oxygen species (ROS). These ROS can then stimulate the surrounding cells to secrete inflammatory cytokines, eventually leading to increased leukocyte infiltration into the brain. This type of prolonged stroke-induced inflammation in the brain can result in several detrimental effects. For one, infiltration and aggregation of leukocytes may directly lead to further injury through their secretion of harmful substances. Also, the blood brain barrier can be compromise by the activation of cytotoxic releasing inflammatory cells. This can lead to edema (an accumulation of fluid) in the brain, which can further exacerbate damage caused by low oxygen levels.

Due to the 3-hour timetable for TPA (tissue plasminogen activator) effectiveness, 95% of strokes cannot be treated specifically. Also, a study done by the WHO concluded that the best acute care for stroke patients can only slightly improve outcomes. Both of these statements further justify the continued research towards better understanding the many factors involved in delayed damage mechanisms associated with stroke-induced inflammation.

This accounts for the sudden onset of inflammation following and directly related to a stroke. Has anyone found information regarding chronic systemic inflammation and its role in stroke?

References:

Dirnagl, Ulrich, and Elger, Bernd. "Neuroinflammation in Stroke". Springer, 2004. Pg: 87-95.

Tang, Xian Nan, Wang, Qing, and Yenari, Midori A. "The Inflammatory Response in Stroke". J. Neuroimmunol. 184(1-2): 53-68.

Inhibitors in Hemophilia: A Potentially Devastating Problem

Hemophilia A affects about 1/5000 males, is typically inherited, and is normally treated with factor VIII (F8) replacement therapy. However, factor replacement therapy has a major side effect-inhibitors occur in approximately 25% of those with severe hemophilia A, and are a direct result of factor replacement therapy. Inhibitors are antibodies that neutralize the function of F8, which means that the F8 replacement that is being used to treat bleeding episodes (to stop the bleeding or prevent the bleeding) isn’t effective (and so the bleeding doesn’t stop)!

Why do inhibitors develop in hemophilia?
Severe hemophilia is the result of a mutation in the F8 gene that renders the protein useless. Some mutations result in the complete loss of the protein (large deletions and nonsense mutations) whereas others result in a protein that isn’t functional (missense mutations and splice site mutations). If a mutation results in complete loss of the F8 protein, then when F8 is introduced as part of replacement therapy, the protein is foreign to the body!

So, what about the immunology?
First, not all antibodies to F8 are inhibitors (they aren’t all dangerous). Actually, about 15% of healthy blood donors have non-pathogenic F8 antibodies. CD4+ T-cells play a role in anti-F8 antibody synthesis. Like any other protein, F8 is processed into peptides by an antigen-presenting cell, presented with MHC class II to a CD4+ T-cell, and, with a proper CD4+ T-cell receptor and with costimulation, the CD4+ cell directs B cells to make antibodies. Both Th1 and Th2 cells contribute to the production of anti-F8 antibodies, and the proportion of the Th1/Th2 response is unique to the individual. In addition, it appears that the pathogenic immune response to F8 is the result of failure to activate regulatory CD4+ cells specific for certain F8 sequences.

Why does it matter?
Inhibitor development, especially if the inhibitor develops at a high titer, can be devastating for those with severe hemophilia. In extreme cases, where factor replacement therapies don’t work, some patients turn to “immune tolerance therapy,” in which the patient is exposed to high doses of F8 daily for weeks and even years, sometimes in conjunction with immunosuppressive drugs. The idea is to tolerize the body to the F8 (teach the body not to mount an immune response to the F8), and according to the National Hemophilia Foundation, works about 60-80% of the time. Interestingly, patients who respond successfully to immune tolerance or immunosuppressive therapies tend to have a predominance of Th1-driven antibodies, whereas those who fail to respond to these therapies tend to have a Th2-driven response.

References
National Hemophilia Foundation (http://www.hemophilia.org/)
M.T. Reding, “Immunological aspects of inhibitor development,” Haemophilia, 12 (Suppl. 6) 30-36, 2006.

Hepatitis C Vertical Transmission

As a Pediatric Gastroenterology Fellow I have an interest in Hepatitis C (HCV) Vertical Transmission (transmission from mother to child). I am in the midst of designing a study to look at the immune activity in mothers at the time of delivery and infants over the first 12-18 months of life. I hope to find a difference in those who become chronically infected and those infants that do not.

This study is my main motivation for taking Immunology as the study is very focused on immune function. HCV challenges both the innate and cell-mediated immune systems. We currently know little about either in the pediatric patient.

Let me share some of the background with you.

HCV is a single-stranded RNA virus in the flaviviridae family. The virus has significant viral heterogeneity, including 6 major genotypes and numerous subtypes. The most common subtypes found in the United States (US) are 1a and 1b.1 The high replication rate (1010—1012 virions/day) and error prone polymerase allows for a robust production of minor viral variants. 2 It is estimated that 3% of the world’s population is chronically infected with HCV.3 The prevalence in the US is 1.8%, making it the most common blood borne infection in the US. The prevalence in the general pediatric population varies between 0.1% and 15% worldwide.4 The US pediatric HCV prevalence is 0.2% for children less than 12 years old and 0.4% for those between 12-19 years old.5

Vertical transmission of Hepatitis C virus (HCV), accounts for the majority of new cases of Pediatric HCV. Vertical transmission rates are between 2 and 14%.6 If the mother is known to be anti-HCV antibody (Ab) positive, but is HCV RNA negative, vertical transmission is very rare.7 Several studies have shown an increased risk for vertical HCV transmission associated with maternal HIV infection and IV drug use.1, 8, 9 Maternal alanine aminotransferase (ALT) and viral load have been shown to affect vertical transmission rates, with an elevated ALT >110 IU/L and a viral load of greater than 105 copies/ml associated with an increased risk for vertical transmission.6 The European Pediatric HCV Network found an increase in vertical transmission to female infants compared to male, with females twice as likely to become infected.3 This supported Granovsky’s findings that female infants were infected more frequently than males (8% vs. 3%).10 The European Network found that the duration of rupture of membranes was longer in maternal child pairs with transmission of HCV (> 6 hours) compared to those without, although this difference was not statistically significant.3 No significant correlation has been found for the type of delivery or breastfeeding. 1, 5 Maternal HCV genotype has not been shown to impact the rate of vertical transmission.6

The diagnosis of vertical transmission, transmission of infection from mother to infant, of HCV is complicated by transplacentally acquired maternal anti-HCV antibodies that can persist for up to 18 months following delivery. Seventy percent of vertically infected infants will have a positive HCV RNA PCR by 1 month of age and 90% by 3 months of age.1 If infected, children and their mothers have identical HCV genotypes.8 The diagnosis of chronic Hepatitis C is established by 2 positive HCV RNA PCRs from serum 3 to 4 months apart in an infant who is at least 2 months of age and/or by detection of anti-HCV antibodies after the infant is 18 months old.9,1
All infants born to Anti-HCV Ab positive mothers will have circulating IgG antibodies to HCV at birth. 99% of children lose the Anti-HCV antibodies within 18 months of delivery if they are negative for HCV RNA. Chronic infection is most often asymptomatic in childhood; however elevation of transaminases is quite common.4 Typically liver disease remains mild for the first 1 or 2 decades.5 A small portion of perinatally infected children have developed advanced liver disease during childhood accounting for 9 liver transplants in North America between 1995 and 2001.5 HCV remains a leading diagnosis resulting in liver transplant in the adult population.

One study from Italy began the investigation into the role of fetal immune activity in the vertical transmission of HCV. This study demonstrated Hepatitis C virus-specific reactivity of CD4+ lymphocytes in children born to HCV-infected women. HCV-specific T-cells were more frequent and vigorous in children than in their HCV positive mothers. This study demonstrated that vertical exposure to HCV induces a Hepatitis C virus-specific cell-mediated immune response. The authors hypothesized that development of a robust HCV directed cell-mediated immune response during fetal life may contribute to the relatively low frequency of vertical transmission.14 There are no other published systematic studies of immune cell function in infants at risk for vertical transmission. Currently, there are several completed and ongoing trials investigating the immune cells function in the role of HCV clearance in adult patients.

Meyer demonstrated clearance of infection in male German youth from 16 to 24 years old with a weak HCV-specific CD4+ t-cell response.15 In this study there was no difference between acute and chronically infected subjects CD4+ response. 15 This study proposed that the low levels of viremia are controlled by the innate immunity without a strong adaptive immune response. 15

Fetal immune activity has been shown to be biased towards the Th2 response for protection of the fetal-maternal interface. The Th2 predominant response results in suppression of Th1 activity. 16 Fetal CD4+ T-cells have low cytokine production and decreased numbers of mononuclear phagocytes resulting in a weak innate immune response. While the fetal immune response to HCV has not been fully examined, the decreased Th1 activity may play a role in chronic infection resulting from vertical transmission.16

The immune response seen in chronic HCV has been shown to be weak and directed at a limited number of epitopes when compared to the response seen in spontaneous clearance.17 The immune response seems to quickly compartmentalize to the liver with evidence that HCV may upregulate homing molecules involved in T cell recruitment.17 There are conflicting reports regarding the role of HCV specific CD8+ T cells in chronic infection.17 CD8+ T cells have been associated with variable amounts of liver injury and a range of viral loads.17

Viral clearance is generally attributed to a robust induction of cell-mediated immune response including type 1 interferon, cytotoxic T lymphocytes (CTL) and natural killer cells (NK).15, 18, 19The role of dendritic cells includes viral recognition and activation of pathways for IFN – Beta production and Nk/CTL induction. The role of dendritic cells in childhood HCV infection has not yet been evaluated.18

Cytotoxic lymphocytes include cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cells) that are responsible for eliminating damaged cells and play a key role in mediating host response to viral infection. CTLs are MHC-Class I restricted CD8+ T cells that migrate into affected tissue in association with the MHC Class I complex and suppress viral replication by cytolysis and secretion of antiviral cytokines. One study in adults demonstrated a functional T-cell threshold that predicted recovery from acute HCV infection.20 NK cells work through rapid and potent cytotoxic activity and by production of inflammatory cytokines, such as IFN-γ.17 NK cells provide a first line of defense against viral infections, and are critical for the development of Antigen-specific memory.19 The activity of NK cells is controlled by receptors (NKRs) that mediate activation or inhibition upon ligation of surface molecules on target cells.17, 21Alterations in NK function can create a situation where the virus may have a replicative advantage leading to a high level of viremia that cannot be controlled by memory T cells.18

CD4+ T lymphocytes regulate CTL memory via cytokine production and by assisting antigen-presenting cells. CD4+ T cells also are important in IL-2 production. In adults with HCV, levels of HCV-specific CD4-derived IL-2 were significantly higher in patients who cleared the HCV infection.20 These data suggest that CD4+ lymphocytes might play a role in the prevention of vertical transmission of HCV or the resolution of infection.

Understanding the role of cell-mediated immunity in the regulation of vertical acquisition or clearance of HCV is the first step in identifying infants at risk for chronic infection. This study will describe cell-mediated immune activity that could provide the first step in a process leading to early treatment regimens that target infants at highest risk for chronic HCV infection.

References
Airoldi J, Berghella, V. Hepatitis C and pregnancy. Obstetrical and Gynecology Survey. 2006 2006;61(10):666-671.
2. Uebelhoer L HJ, Callendret B, Mateu G, Shoukry N, Hanson H, Rice C, Walker C, Grakoui A. Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness. PLOS Pathogens. September 2008 2008;4(9):e1000143.
3. Network EPHCV. A significant sex - but not elective cesarean section - effect on mother-to-child transmission of hepatitis C virus infection. J. Infect Dis. 1 Dec 2005 2005;192:1872-1879.
4. Fischler B. Hepatitis C virus infection. Seminars in Feral and Neonatal Medicine. 2007 2007;12:168-173.
5. Jonas M. Children with Hepatitis C. Hepatology. Nov 2002 2002;36(5, Suppl 1):S173-S178.
6. Hayashida A, Inaba, N., Oshima, K., Nishikawa, M., Shoda, A., Hayashida, S., Negishi, M., Inaba, F., Inaba, M. Re-evaluation of the true rate of hepatitis c virus mother-to-child transmission and its novel risk factors based on our two prospective studies. J. Obstet. Gynaecol. Res. Aug 2007 2007;33(4):417-422.
7. Yeung LT KS, Roberts EA. Mother-to-infant transmission of hepatitis C virus. Hepatology. 2001 2001;34:223-229.
8. Resti M, Azzari, C., Mannelli, F., Moriondo, M., Novembre, E., Martino, M., Vierucci, A., . Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. BMJ. 15 Aug 1998 1998;317:437-441.
9. Mast E, Hwang, L., Seto, D., Nolte, F., Nainan, O., Wurtzel, H., and Alter, M. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J. Infect Dis. 1 Dec 2005 2005;192:1880-1889.
10. Granovsky MO MH, Tess BH, Waters D, Hatzakis A, Devoid DE, Landesman SH, Rubinstein A, DiBisceglie AM, Goedert JJ. . Hepatitis C Virus Infection in the Mothers and Infants Cohort Study. . Pediatrics. 1998 1998;102:355-359.
11. Narkewicz M, Cabrera, R., Gonzalez-Peralta, R. The "C" of Viral Hepatitis in Children. Seminars in Liver Disease. 2007;27(3):295-311.
12. Bortolotti F, Verucchi, G., Calogero C., Cabibbo G., Indolfi, Z., Giacchino, R., Marcellini, M., Marazzi, M., Barbera, C., Maggiore, G., Vajro, P., Bartolacci, S., Balli, F., Maccabruni, A., Guido, M. Long-term Course of Chronic Hepatitis C in Children: From Viral Clearance to End-Stage Liver Disease. Gastroenterology. June 2008 2008;134(7):1900-1907.
13. Yeung L, To, T., King, S., Roberts, E. Spontaneous clearance of childhood hepatitis C virus infection. Journal of Viral Hepatitis. 2007 2007;14:797-805.
14. Della Bella S, Riva, A., Tanzi E., Nicola, S., Amedola, A., Vecchi, L., Nebbia, G., Longhi, R., Zanetti., A., Villa M. Hepatitis C virus-specific reactivity of CD4+ lymphocytes in children born from HCV-infected women. J. Hepatology. 2005 2005;43:394-402.
15. Meyer M, Lehmann, M., Cornberg, M., Wiegand, J., Manna, M., Klade, C., Wedemeyer, H. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response. Virology Journal. 11 June 2007 2007;58(4):1-11.
16. Marodi L. Innate cellular immune response in newborns. Clinical Immunology. 2006;118:137-144.
17. Ishii S, Koziel, M. Immune responses during acute and chronic infection with hepatitis C virus. Clinical Immunology. 2008;128:133-147.
18. Ebihara T, Shingai, M., Matsumoto, M., Wakita, T., Seya, T. Hepatitis C Virus-Infected Hepatocytes Extrinsically Modulate Dendritic Cell Maturation To Activate T Cells and Natural Killer Cells. Hepatology. July 2008 2008;48(1):48-58.
19. Rauch A, Laird, R., McKinnon, E., Telenti, A., Furrer, H., Weber, R., Smillie, D., Gaudieri, S., and the Swiss HIV Cohort Study. Influence of inhibitory killer immunoglobulin-like receptors and their HLA-C ligands on resolving hepatitis C virus infection. Tissue Antigens. 2007;69:237-240.
20. Smyk-Pearson S, Tester, I., Klarquist, J., Palmer, B., Pawlotsky, J., Golden-Mason, L., Rosen, H. Spontaneous recovery in acute human hepatitis C virus infection: functional T-cell thresholds and relative importance of CD4 help. J. Virol. Feb 2008 2008;82(4):1827-1837.

Lymphatic Pump Increases Immune Response

In the past decade there has been a growing interest in osteopathic manipulative medicine. A Doctor of Osteopathic (DO) have the same benefits and training to practice as an Allopathic Doctor (MD), but are trained to treat holistically by examining the whole body versus the symptomatic approach of allopathic medicine. In addition, DOs have the benefit of manipulation to induce the body’s self-healing process and to reduce injury and diseases. A few manipulation techniques include: muscle energy (muscle contraction), strain-counterstrain (localizing and reliving painful spots), myofascial release (gentle force to reduce neurological muscle tightness), and lymphatic pump treatment (increase lymph flow). The lymphatic pump treatment (LPT) is particularly interesting in terms of treating patients with edema and infections.

The lymphatic system is organized as a network of fluid collecting vessels in order to maintain macromolecular homeostasis, lipid absorption, and lymphocyte transportation. The lymph system serves as a reservoir of surplus tissue fluid, known as lymph, and the removal of cellular debris from cellular breakdown and infection. Unlike the circulatory system where the heart pumps blood through the body, the lymphatic vessels depend on the contraction/relaxation or compression/expansion of the lymphatic vessels via skeletal muscle movements and lymphatic valves. In summary, the movement or contraction of the skeletal muscles allows the lymph to flow against a gradient or gravity, and the valves on each vessel segment prevent the backflow of the lymph.

Studies have shown that LPT indirectly increases lymph flow and patient’s immune response to infections, but have not shown firm evidence that patients benefit from LPT. Current and ongoing research, however, are finding that LPT not only increases lymph flow but increases leukocyte count and flux.

H. Fred Downey et al. has conducted studies on dogs to determine if LPT and exercise changes lymph flow with or without the expansion of extracellular fluid volume (ECE). They have concluded that LPT with ECE greatly increases lymph flow rate than just LPT alone and is found to be similar with exercise; however, exercise was found to have higher lymph flow rate than LPT.

In another study conducted by Lisa Hodge et al., LPT was found to increase leukocyte count and flux. During LPT, lymph was collected and discovered to have an increase in macrophages, neutrophils, total lymphocytes, and T and B cell counts. They concluded that the increase in lymph flow during LPT enhanced the mobilization of lymphocytes and maybe responsible for patients’ improved immune responses.

With these data, it can be suggested that LPT would most benefit patients who are well hydrated and are partially or wholly immobilized (astronauts or individuals with paralysis or muscular diseases). Many have suggested that moderate exercise during a viral or bacterial infection helps to “sweat out the illness”, or in scientific terms increase lymphatic and lymphocyte flow to fight off the infection.

I have never tried LPT or exercised at the peak of a cold (the thought of exercising when feeling terrible just does not sound appealing), but has anyone in our group tried or knows anyone who have done these strategies and recovered quickly from a viral or bacterial infection?


References:

Degenhardt, Brian. (2000). Osteopathic manipulative medicine: Optimizing patient-focused health care. The Advisor, 21(1). Retrieved September 28, 2008, from
http://www.aacom.org/about/osteomed/Pages/Degenhardt.aspx

Downey, H. Fred. (2008). Lymph flow in the thoracic duct of conscious dogs during lymphatic pump treatment, exercise, and expansion of extracellular fluid volume. Lymphatic Research and Biology, 6(1), 3-13.

Hodge, Lisa. (2007). Abdominal lymphatic pump treatment increases leukocyte count and flux in thoracic duct lymph [Abstract]. The Journal of Immunology, 178(99), 13. Retrieved from PubMed database.

Knott, Marty E. (2005). Increased lymphatic flow in the thoracic duct during manipulative intervention. Journal of the American Osteopathic Association, 105(10), 447-456.

Zawheja, David. (2005). Lymphatic biology and the microcirculation: Past, present, and future. Microcirculation, 12, 141-150.

website

sorry it didnt post the website
http://aje.oxfordjournals.org/cgi/content/abstract/160/4/376

Stroke and Inflammation

Thank you so much for the overview on strokes! it really helped to have it in easy to understand an relevant format.
I just wanted to start off with the lay articles:
The first being the "Timing is Key" I never knew that there was a window of around 3 hours to get to the hospital while having a stroke. I always thought it was a spontaneous occurrence that couldn't be stopped after it had started. Also, I knew there were symptoms but I didn't know that they were precursors that once identified could help save the person from farther damage.
The second article which talks about the higher occurrence of stroke in Mexican Americans already has a post on it but i found this article that helps:

this article kind of explains a difference and it also states that "there are no existing data regarding the cerebrovascular disease burden faced by Mexican Americans, and estimates regarding the impact of stroke on the nation are therefore limited."

While reading the article on Nitric Oxide, I was somewhat confused and had to read it twice and I'm still sort of unclear on whether which is beneficial and which is not. Even at the end of the paper it says that it can be both. At one point is says that NOS1 and NOS2 are beneficial and that NOS3 is not but it then stays that studies are in conclusive. Just wondering if anyone figured it out?

The last articles discusses the inflammatory effects of stroke, but I'm wondering if there are any inflammatory precursors for stroke. I found on the American Heart Association website (http://www.americanheart.org/presenter.jhtml?identifier=4648) and they discussed CRP's (C-reactive proteins) and their effect on the cardiovascular system, which we have talked about before. I just think it's a good cross over between diabetes that we discussed before and now stroke. It is interesting the the same CRP's can lead to multiple issues in the body that can cause a variety of events.

Video links depicting 2 different types of stroke

Animation of a hemorrhagic stroke
http://www.stroke.org/site/DocServer/Hemorrhagic_stroke_ani.mpg?docID=2821
Animation of an ischemic stroke
http://www.stroke.org/site/DocServer/Ischemic_Stroke_ani.mpeg?docID=2822

I would also recommend looking over the fact sheet from this site (http://www.stroke.org) for an overview.

Stroke overview

Thought I would post a brief review about the various types and causes of stroke before the upcoming week.

There are 2 types of stroke: Ischemic and Hemorrhagic, each with several subtypes. At this point in time we believe that inflammation plays a larger role in Ischemic rather than hemorrhagic stroke.

In an Ischemic stroke blood clots form, block arteries and cut off blood flow. An ischemic stroke can occur in one of two ways. The first is an Embolic stroke during which a blood clot forms somewhere in the body (most commonly the heart) and travels through the blood stream to the brain. The clot eventually travels in the brain to blood vessels small enough to block its passage. Once lodged, the clot causes a stroke known as an embolus. The second type of ischemic stroke is a Thrombotic stroke. In a thrombotic stroke blood flow is impaired due to a blockage in one or more of the arteries supplying blood to the brain. The process that leads to the blockage is known as thrombosis and the subsequent clot that is formed is known as a thrombus.

Strokes that are caused by blood clots can happen as a result of blood vessels that are clogged with build up of cholesterol. The body reacts to these build ups as multiple, tiny and repeated injuries to the vessel wall; responding as it would to any other wound in the body and forms a clot. Two types of thrombosis can cause stroke: large vessel thrombosis and small vessel disease (or lacunar infarction). Large vessel thrombosis is the most common and best understood type of thrombotic stroke. Large vessel thrombosis is most often caused by a combination of long-term atherosclerosis that is followed by rapid clot formation. Patients that suffer a thrombotic stroke are also likely to have coronary artery disease and a heart attack is frequently the cause of death in patients who have suffered this type of brain attack. The second cause of thrombosis is small vessel disease or a lacunar infarction. This type of disease occurs when the blood flow is blocked to a very small arterial vessel. The term lacunar infarction comes from the Latin word lacuna which means hole and describes the small cavity remaining after the product of deep infarction have been resolved by other cells in the body. Small vessel disease is most likely linked to hypertension, however we know the least about this disease.

The second major type of stroke is a hemorrhagic stroke, caused by the breakage or "blow out" of a blood vessel in the brain. A hemorrhage can be caused by a number of disorders that affect the blood vessels, including long term hypertension and cerebral aneurysm. An aneurysm is a very weak or thin spot on a blood vessel wall that is usually present at birth. Aneurisms develop over a number of years and usually do not cause any detectable problems until they break. There are two types of hemorrhagic stroke: subarachnoid and intracerebral. An intracerebral hemorrhage causes bleeding from within the brain itself with hypertension usually being the primary cause of this hemorrhage. In a subarachnoid hemorrhage an aneurysm bursts in a large artery or near the thin, delicate membrane surrounding the brain. Blood spills into the area around the brain, causing the protective fluid to become contaminated with blood.

Information taken adapted from http://www.stroke.org 9/28/08

The lay article "As if One Stroke Weren't Enough..." stated Mexican-Americans and African-Americans are much more susceptible to stroke than non-Hispanic white Americans. From other classes I also know that people in the Mediterranean area are also much more likely than Americans to suffer from stroke and it made me think that maybe there is some sort of genetic component that these people have that white Americans do not. Is anyone aware of research to this matter?