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Jeepgun
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Hypothalamus -- Crackin' The Brain
« on: Jul 22nd, 2004, 1:21pm »
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Good link, and lots of info about the brain.
http://en.wikipedia.org/wiki/Hypothalamus
 
From one of my anatomy and physiology textbooks:
 
Hypothalamus disorders
 
Damage to the hypothalamus can result from surgery, trauma (such as accident or stroke), degeneration due to old age or disease, or a tumor. The results of damage can be varied and depend on the areas of the hypothalamus involved.
 
Diabetes insipidus can be caused by hypothalamic damage, or by damage to the hypothalamic-pituitary tract. This disease reduces vasopressin production, resulting in large volumes of urine being produced at all times. [wait: This sounds like fun! You could be one of those cherub fountains, but like, ALIVE!!] Grin
 
Other hypothalamic disorders can include sexual abnormalities (such as premature puberty), psychic disturbances, obesity, anorexia, temperature regulation disorders, sleep disorders, and disruption of normal circadian rhythms.

 
« Last Edit: Jul 22nd, 2004, 1:29pm by Jeepgun » IP Logged
floridian
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Re: Hypothalamus -- Crackin' The Brain
« Reply #1 on: Jul 22nd, 2004, 1:29pm »
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Edited that entry.  Added a statement about circadian cycles, and linked it to the wikipedia cluster headache article.  Great pictures of the hypothalamus, though the text is limited.  I may revisit that when I get more time.  
 
I was building a cluster headache wiki at swiki.net, but their service is flaky - I think they deleted a few days of my life.  Will try to find a better provider and start over - the vision is a (hyper) book on clusters - up to date, free, etc.
« Last Edit: Jul 22nd, 2004, 1:32pm by floridian » IP Logged
Jeepgun
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Re: Hypothalamus -- Crackin' The Brain
« Reply #2 on: Jul 22nd, 2004, 1:30pm »
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Huh?
 
Oh. Okay. Thanks for the clarification. (If I would have known the info was out there, I wouldn't have gone through the effort to type it all. LOL)  Smiley
« Last Edit: Jul 22nd, 2004, 1:35pm by Jeepgun » IP Logged
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Re: Hypothalamus -- Crackin' The Brain
« Reply #3 on: Jul 22nd, 2004, 1:35pm »
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I edited the wikipedia entry for the hypothalamus.  Anybody can.  The wikipedia article on cluster headaches was also very short, but I rewrote it (with help from Wendy/Pubgirl).  Some wikis are like grafiti walls - anyone can change anything.  But wikipedia works because people police areas they are interested, remove grafitti, etc.  Each edit is logged, so a wiki can be rolled back to a previous state.  
 
I'm looking for a wiki hosting service that allows control over who can edit.  I think I have found one, but if there are any wiki gurus, please advise.
« Last Edit: Jul 22nd, 2004, 1:37pm by floridian » IP Logged
Jeepgun
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Re: Hypothalamus -- Crackin' The Brain
« Reply #4 on: Jul 22nd, 2004, 1:43pm »
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Because it does link the nervous and endocrine systems, could this be the reason that drugs like lithium seem to work as a preventative to CH?
 
Drugs like Verapamil would reduce blood pressure, thus having what effect? Would it be to reduce the amount of blood flow, or to slow down (reduce pressure) the blood flow through the brain?
 
And if it does that, then does the amount and frequency of cellular activity decrease to normal levels?
 
How does oxygen affect it? If the blood has a high enough saturation level, then the pulse rate slows because all systems of the body are communicating that they have enough oxygen. Does this cause cellular activity to decrease?
 
All of this is assuming that an increased cell-density and activity within the hypothalamus is what may be the cause of cluster headache attacks...
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floridian
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Re: Hypothalamus -- Crackin' The Brain
« Reply #5 on: Jul 22nd, 2004, 1:56pm »
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on Jul 22nd, 2004, 1:43pm, Jeepgun wrote:
Because it does link the nervous and endocrine systems, could this be the reason that drugs like lithium seem to work as a preventative to CH?
 
Drugs like Verapamil would reduce blood pressure, thus having what effect? Would it be to reduce the amount of blood flow, or to slow down (reduce pressure) the blood flow through the brain?
 
And if it does that, then does the amount and frequency of cellular activity decrease to normal levels?
 
How does oxygen affect it? If the blood has a high enough saturation level, then the pulse rate slows because all systems of the body are communicating that they have enough oxygen. Does this cause cellular activity to decrease?
 
All of this is assuming that an increased cell-density and activity within the hypothalamus is what may be the cause of cluster headache attacks...

 
Yes, No, and Hmm.  
 
Lithium's action is not really understood for bipolar disorder, although many thousands of studies have been done on that topic.  It is even less understood in clusters.  But it is linked to the nervous and endocrine systems as you suggest.  I think it is related to lithium's ability to turn certain genes on or off - but which ones are key, and which ones are side effects??  Wish I knew.  
 
Verapamil doesn't seem to help clusters by lowering blood pressure - it is a calcium channel agonist that affects how calcium moves in and out of the cells.  
 
Oxygen ?  Not sure.  Oxygen has a variety of effects - changes blood vessel tone, changes nerve activity, changes pH of blood, etc etc etc.   One study on hyperbaric oxygen suggested that 10-15 sessions of that could change how blood cells bind and release serotonin.  
 
The hypothalamus is definitely involved in clusters.  Part of it is visibly different and not working properly.   This breakdown can lead to changes across the body.  But no one has a proven, all encompassing explanation yet.  
 
(edited 2:25  blood pressure tone changed to blood vessel tone. )
« Last Edit: Jul 22nd, 2004, 2:22pm by floridian » IP Logged
Jeepgun
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Re: Hypothalamus -- Crackin' The Brain
« Reply #6 on: Jul 22nd, 2004, 1:59pm »
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Seratonin! Now that's interesting... Out of all the clusterheads that showed up in Nashville, I think there were only two who were not smokers. A number of studies have been done on nicotine and how it affects the release of seratonin in the brain. Goddammit... It's like having half a box of puzzle pieces!! It's all connected, but good luck with ever making it look like a complete picture.  Angry
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Re: Hypothalamus -- Crackin' The Brain
« Reply #7 on: Jul 22nd, 2004, 2:12pm »
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Interesting discussion...
 
My understanding of O2 is that when higher levels of psO2 are experienced by the brain, it compensates by causing a constriction of blood vessels. Of course, in the midst of a clusterheadache, this is a good thing.
 
Verapamil is a tougher nut to crack. The calcium channel blocker serves to interrupt the signals with smooth muscle & may lead to a reduction in the responsiveness of blood vessel contraction/dialation. It would seem at the outset, that verapamil would make things worse, but it doesn't.
 
As for the smoking ... I'm one of those two Jeep. For a non-smoker, I seem to be very responsive to both oxygen & verapamil. I'm on a low dose of verap & O2 works for me 100% of the time. I wonder if by not smoking, my seratonin levels are less out-of-wack and therefore I respond better to treatments? Who knows ... like you said it's a big puzzle and I don't think we've got all the pieces yet.
 
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Jeepgun
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Re: Hypothalamus -- Crackin' The Brain
« Reply #8 on: Jul 22nd, 2004, 2:16pm »
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Well, not to throw a wrench into your theory on Verapamil, but my last cycle, I was on the lowest dose possible, and it worked like a charm.  
 
Another interesting experience: A couple of years ago, I was trying to quit smoking and I was on Wellbutrin. For whatever reason, a nice side-benefit, was that it kept a good portion of the cluster headaches at bay. Then again, Wellbutrin is a mild anti-depressant, so I'm betting it also has an effect on seratonin...  
 
Okay: Maybe it's like having half of the pieces to a whole shitload of puzzles!!  laugh
« Last Edit: Jul 22nd, 2004, 2:17pm by Jeepgun » IP Logged
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Re: Hypothalamus -- Crackin' The Brain
« Reply #9 on: Jul 22nd, 2004, 4:12pm »
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The oxygen bit is interesting in that it works 100% of the time for Bruce and countless others. I am not in that group. I have at most a 70% success rate. During the presentation (or maybe it was later??) Dr. Volcy said that there is a higher failure rate for smokers (heavy smokers, would be my guess) and O2.
 
Do smokers have more nitric oxide (NO)? and if so, why is it a relief to smoke for some? Aren't you increasing the chances of an attack. I'm not saying that quitting smoking would astop clusters, far from it. That has been discussed to death already. I'm just saying that smoking may be blocking some us from complete relief using O2.
 
Ozzy
 
PS. I was going to ask about CGRP agonists and antagonists but that I'll save for another thread, another day
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floridian
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Re: Hypothalamus -- Crackin' The Brain
« Reply #10 on: Jul 22nd, 2004, 4:31pm »
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Complicated stuff. Smoke contains a fair dose of nitric oxide.  Smoking seems to turn down the bodies own nitric production.  My guess is that when someone is getting hit by the beast, nitric oxide is very high at the trigeminal nerve, and that smoking doesn't impact it one way or the other - the short term soothing effect is from some other mechanism.  
 
Quote:
Nicotine Tob Res. 2002 Aug;4(3):341-8.  
 
    The role of nitric oxide in cigarette smoking and nicotine addiction.
 
    Vleeming W, Rambali B, Opperhuizen A.
 
    National Institute of Public Health and Environment, Laboratory of Health Effects Research, PO Box 1, NL 3720 BA Bilthoven, The Netherlands. W.Vleeming@rivm.nl
 
    The purpose of this study is to describe the interrelationship between nitric oxide (NO) and nicotine in cigarette smoking addiction, in view of the underlying hypothesis that NO contributes to smoking (nicotine) addiction, and to suggest the ways to improve prevention as well as cessation strategies. A literature search of Medline using the keywords nicotine and nitric oxide covering 1995 to May 2001 was made. Further information not obtained from the Medline search was derived from the references cited in these publications. Smokers are exposed first to high concentrations of inhaled NO from smoke and, second, to endogenously released NO after uptake of nicotine into the brain. As a result, the basal endogenous NO synthesis in airways and blood vessels of smokers is reduced. Subsequently, because NO is involved in maintaining airway dilatation, smokers may have constricted airways. During smoking, however, NO from smoke may dilate the constricted airways, allowing the smoke an easier passage into the lungs, and exposing the body and the brain to more nicotine. NO can endogenously be released by nicotine from nervous tissue, and may decrease the sympathetic output of the brain, which is associated with stress reduction. This second form of exposure to NO also inhibits the re-uptake of dopamine, which may contribute to dopaminergic receptor stimulation and thus to the acute rewarding effects of nicotine. The important role of NO in nicotine addiction is further supported by the finding that in animals NO synthase (NOS) inhibitors attenuate symptoms of the nicotine abstinence syndrome. NO may contribute to the development of cigarette smoking and nicotine addiction since: (1) inhaled NO from smoke may be able to increase nicotine absorption, (2) NO released through nicotine reduces symptoms of stress, (3) NO endogenously released by nicotine increases post-synaptic dopamine levels, and (4) NOS inhibitors attenuate symptoms of the nicotine abstinence syndrome. It remains to be determined whether reducing the NO content in cigarette smoke may reduce nicotine absorption. It also needs to be clarified whether NOS inhibitors or a low L-arginine diet might be useful in the treatment of nicotine addiction.

 
Quote:
Drug Metab Dispos. 2003 Jul;31(7):932-7.  
     
    Metabolism-based inactivation of neuronal nitric-oxide synthase by components of cigarette and cigarette smoke.
 
    Demady DR, Lowe ER, Everett AC, Billecke SS, Kamada Y, Dunbar AY, Osawa Y.
 
    Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.
 
    It has been shown that administration of cigarette smoke to rats leads to loss of neuronal nitric-oxide synthase (nNOS) activity and nNOS protein in penile tissue. The exact mechanism for this loss of activity and protein is not known. In the current study, we investigated whether extracts prepared from cigarette smoke or from the cigarette itself could directly inhibit nNOS activity. We discovered that the cigarette smoke extract and the cigarette extract cause a time-, concentration-, and calmodulin-dependent inactivation of nNOS in an in vitro system containing the purified enzyme. L-Arginine, but not D-arginine, protects nNOS from this time-dependent inactivation, suggesting an active site directed event. The kinetics of inactivation are consistent with the metabolism-based or suicide inactivation of nNOS. Based on studies with other metabolism-based inactivators, this cigarette-mediated inactivation may render nNOS more susceptible to proteasomal degradation and thereby may explain the loss of nNOS protein in vivo. The component(s) responsible for nNOS inactivation is not volatile, is not retained by a 3,000 molecular weight cut-off membrane, binds to activated charcoal, and is highly water-soluble under both acidic and basic conditions. The discovery of a direct inactivation of nNOS by an organic, cationic compound(s) present in tobacco and tobacco smoke provides a basis for further study of not only the mechanisms responsible for the biological effects of tobacco but also a search for a potentially novel inactivator of nNOS.
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Re: Hypothalamus -- Crackin' The Brain
« Reply #11 on: Jul 22nd, 2004, 4:36pm »
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Smoking does increase CGRP levels.  In general, that could be bad, but it doesn't explain the intense pain of a cluster.  With clusters, it isn't a constant increase of the background level - it is a sudden, dramatic increase in one particular region of the head.  Something isn't being controlled properly - not getting the right signals.  
 
Quote:
Am J Respir Cell Mol Biol. 2001 Sep;25(3):299-305.  
     
    Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs.
 
    Kwong K, Wu ZX, Kashon ML, Krajnak KM, Wise PM, Lee LY.
 
    Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA.
 
    This study tests the hypothesis that the bronchial hyperreactivity induced by chronic cigarette smoke (CS) exposure involves the increased expression and release of tachykinins and calcitonin gene-related peptide (CGRP) from afferent nerve fibers innervating the airways. In guinea pigs chronically exposed to CS (20 min twice daily for 14-17 d), peak response in total lung resistance to capsaicin (1.68 microg/kg, intravenously) was significantly greater than that evoked by the same dose of capsaicin in control (air-exposed) animals. This augmented response in CS-exposed animals was abolished after treatment with CP-99994 and SR-48968, the neurokinin (NK)-1 and NK-2 receptor antagonists, suggesting the involvement of tachykinins in chronic CS-induced airway hyperresponsiveness (AHR). Further, substance P (SP)-like immunoreactivity (LI) and CGRP-LI in the airway tissue were significantly greater in the CS animals than in the control animals. Finally, beta-preprotachykinin (PPT, a splice variant from the PPT A gene encoding tachykinins including SP and NKA) messenger RNA levels as measured by in situ hybridization histochemistry displayed a significant increase in jugular ganglion neurons but not in dorsal root or nodose ganglion neurons. These data suggest that chronic CS-induced AHR is related to an increase in SP synthesis and release in jugular ganglion neurons innervating the lungs and airways.
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Re: Hypothalamus -- Crackin' The Brain
« Reply #12 on: Jul 22nd, 2004, 4:46pm »
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Could be that CGRP is produced in response to a lack of oxygen - this article suggests that it protects against ischemia (lack of oxygen).  This would be consistent with the apnea evidence.... saturating the blood with O2 blocks further production of CGRP, thus aborting the headache within a few minutes??    
 
Quote:
Resuscitation. 2003 Oct;59(1):139-45.  
     
    Calcitonin gene-related peptide protects against whole body ischemia in a porcine model of cardiopulmonary resuscitation.
 
    Wu D, Bassuk J, Adams JA.
 
    Department of Research, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140, USA. dwu@msmc.com
 
    The present study was designed to investigate the protective effects of calcitonin gene-related peptide (CGRP) in a porcine model of cardiopulmonary resuscitation (CPR). Twelve pigs were anesthetized, paralyzed, mechanically ventilated with oxygen, and were monitored for electrocardiograph (ECG), arterial pressure, right atrial pressure, airway pressure. Ventricular fibrillation (VF) was induced in all animals by the application of 30 V of alternating current (60 Hz) across the heart, and remained untreated for 3 min, followed by conventional CPR with pneumatic piston device (Thumper) for 15 min. At 18 min of VF a single dose of vasopressin was given, and followed by defibrillation attempts. Two groups were studied. Group 1: Six pigs were used as saline control. Group 2: 0.3 nmol/kg CGRP was given 15 min prior to induction of VF. All animals in the CGRP pretreated group achieved a return of spontaneous circulation (ROSC) and survived more than 2 h (100%), whereas none of the saline control animals achieved ROSC. Blood gases were not significantly different between the groups. However, CGRP group had significantly higher arterial blood pressure and coronary perfusion pressure than control group during CPR. Pretreatment with CGRP affords a cardioprotective effect in this model of whole body ischemia.
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Re: Hypothalamus -- Crackin' The Brain
« Reply #13 on: Jul 22nd, 2004, 4:49pm »
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I smoke more than three packs a day and 02 kills about 99% of my HA's.....I have some really old Zomig Grin
 
Heres another wrench, Ive been chronic more than 29 years but I have not even had a shadow in over four months.....WTF up with that?....No, im not complaining just wondering WTF
 
..............................jonny
 
Edit, I can say that my CH started around the time I started smoking
« Last Edit: Jul 22nd, 2004, 4:55pm by jonny » IP Logged
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Re: Hypothalamus -- Crackin' The Brain
« Reply #14 on: Jul 22nd, 2004, 7:45pm »
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Nice to see this thread... keep the dialogue going...you just never know!
 
Hey, Frank.... Cassandra says HI!!
 
Cathi Tongue
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Re: Hypothalamus -- Crackin' The Brain
« Reply #15 on: Jul 22nd, 2004, 8:26pm »
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Thanks, Cathi! Tell her I said hello and ask her if the Greeks ever finally believed her.  Smiley
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Re: Hypothalamus -- Crackin' The Brain
« Reply #16 on: Jul 22nd, 2004, 8:29pm »
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Frank...she's a CAR-what would SHE know?? LOL...
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Re: Hypothalamus -- Crackin' The Brain
« Reply #17 on: Jul 22nd, 2004, 9:41pm »
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ROFL! Tell her that Jeepster lifted the right front tire in a friendly wave and smiled like this: [O|||||||O]  Grin
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Re: Hypothalamus -- Crackin' The Brain
« Reply #18 on: Jul 22nd, 2004, 9:55pm »
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This is an interesting thread.
 
I am a non-smoker, but grew up in a smoking home, which is when my CH started 26 years ago.
 
I use a low dose calcium channel blocker with good results.
 
And, I take Lexapro and Wellbutrin.
 
Dr. Volcy said something about the Serotonin, but I didn't get it.
 
I do know that during my psych rotation, I asked why the patients got to smoke.  They said the cigarettes actually calm down the patients, especially the ones with schizophrenia.  So the cigarettes have some effect that ties in with a Serotonin imbalance??
 
I feel there is some connection with the serotonin levels.  But how????
 
Little Deb
 
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Re: Hypothalamus -- Crackin' The Brain
« Reply #19 on: Jul 23rd, 2004, 7:20am »
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I haven't had enough coffee yet this morning to totally comprehend all this.
 
My curiosity is this...it was one month after I QUIT smoking that the CH morphed, which added the 12 week hell to my already existing 4-8 days between getting clobbered.  (seeing this subset on Dr. Volcy's chart helped)
 
Of course silly me started smoking again once there was mention of brain tumor by the GP before getting the correct diagnosis, But that didn't change anything as far as the bout was concerned.  I'm sooooo confused now.
 
edit: in addition to the list above on damaged hypothalamus etc....what damage might meningitis do?  Had that at age 14 and it crossed my mind on the plane on the way to Nash.
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Re: Hypothalamus -- Crackin' The Brain
« Reply #20 on: Jul 23rd, 2004, 8:35am »
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Ya' know, after re-reading this whole thread I feel motivated to do more in-depth research. UW has a great med school library & I think I'll start pouring through the research journals to see what I can learn.
 
This thread also reinforces the importance of C.H.A.T.S. Think about it! Everything we've discussed here has been anecdotal. Imagine the power of having hundreds (or even thousands) of clusterhead's histories to go on. The ability to see statistical trends in treatment or onset or whatever ... there's gotta be something in this stuff that will lead to a cure. The only problem that I forsee is apathy. If everyone (and I mean everyone) doesn't take things seriously & keep their C.H.A.T.S information up-to-date, then the system loses its tremendous potential as a research tool.
 
Take care
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Re: Hypothalamus -- Crackin' The Brain
« Reply #21 on: Jul 23rd, 2004, 8:46am »
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You may not even need to go as far as the Medical Library Bruce. I always use this source that Floridian always recommends  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
Pubmed
 
 and I found this site as well, there is much relevant information there:
 
http://www.neurotransmitter.net/
 
 
Ozzy
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Re: Hypothalamus -- Crackin' The Brain
« Reply #22 on: Jul 23rd, 2004, 9:44am »
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Ok one more link, that I just found through the neurotransmitter.net site:
 
http://web.sfn.org/content/Publications/BrainBriefings/index.html
 
The page is called brain briefings, with several neuroscience articles that are easier to understand.
 
Ozzy
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Re: Hypothalamus -- Crackin' The Brain
« Reply #23 on: Jul 23rd, 2004, 9:44am »
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Hey Ozzy,
 
Thanks for the links. I'll have a look at both of them to see what is available.
 
I've used UW's system to access journal abstracts, but I'd like to see full articles on some of the references. Since I'm no longer at the university, I can't access the full text online ... gotta physically go there.  
 
BruceD
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Re: Hypothalamus -- Crackin' The Brain
« Reply #24 on: Jul 23rd, 2004, 10:15am »
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From my understanding, the O2 at 100% high flow rate causes the vessels in the brain to constrict. The brain only requires a certain level of O2--when that level is reached the brain vessels constrict to limit the amount of oxygen thus aborting the headache.
 
Also, interesting discussion on the hypothaolamus.  This kinda show me that DAMAGE could cause our problems as well as probably genic reason.  This might explain why some of us develop this disorder so early and others like me develope it much later in life?
 
John
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