Free-radical brain damage in MODS

Christian Holscher CHOLSCHR at MAIL.TCD.IE
Mon Sep 4 07:31:35 EST 1995


In article <a285-0209951724410001 at d26-ts0.amug.org>, a285 at amug.org (Scott
Tyler) wrote:

> It is ³known² that free radicals play a large part 
> in traumatic, vascular and cryo- brain damage.  It 
> also seems established that cytokineses, etc. in 
> multiple organ dysfunction syndrome/DIC (MODS) cross 
> the BBB and open the BBB to allow free radical access 
> to the brain.
> 
> Question:  is anyone out there studying the above 
> situation?  I have spent a day or so on MEDLARS and 
> don¹t find any articles.  Is there anywhere on the 
> Œnet I should be asking?  
> 
> G. Scott Tyler, M.D.
> a285 at amug.org


I do not know the effects of cytokines and free radicals crossing the BBB,
but it is known that free radicals such as nitric oxide are responisble
for brain damage in traumatic damage. Have a look at these reviews, they
give you the full story.

Moncada S.,Palmer R.M.J. (1992) L-arginine: Nitric oxide pathway. Int.
Soc. Appl. Cardiovasc. Biol. 2, 139:151.

Snyder S.H. (1992) Nitric oxide and neurons. Current Opinion in Neurobiol.
2, 323-327.


NO plays a role in endotoxic and anaphylactic shock as well. It appears
that the synthase that produces NO is induced in macrophages. These are
activated during immune responses and release NO as a 'chemical weapon'.
The large amount of NO released during allergic reactions not only damages
cells but also dilates blood vessels, since NO is a transmitter in blood
vessel dilation. This 'communication error' leads to sudden drop of blood
pressure.

Cytokines also appear to be toxic via a free radical process needed to
synthesize them. See the following article, it is quite broad ranging and
should give you a good idea of the mechanisms:

Rothwell N.J.,Hopkins S.J. (1995) Cytokines and the nervous system II:
actions and mechanisms of action. Trends Neurosci. 18, 130-136.

I hope they are of use to you

christian

-- 
Christian Holscher, PhD
Trinity College Dublin
Dept. Pharmacol. & Therapeutics



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