Melatonin In Traumatic Brain Injury

[ironjustice]

Effect of Melatonin on Intracranial Pressure and Brain Edema Following
Traumatic Brain Injury: Role of Oxidative Stresses.
Dehqan F, Khaksari M, Asadikram G, Nejafipour H, Shahrokhi N.
Arch Med Res. 2013 Apr 19.
Neuroscience Research Center, Kerman University of Medical Sciences,
Kerman, Iran.

Abstract
BACKGROUND AND AIMS: Traumatic brain injury (TBI) is one of main
causes of brain edema and intracranial pressure in (ICP). In the
clinic it is essential to limit the development of ICP after TBI. In
the present study, the effects of melatonin on these parameters at
different time points and alterations of oxidant factors as one of the
probable involved mechanisms have been evaluated.

METHODS: Albino N-Mary rats were divided into five groups of sham,
TBI, TBI + vehicle, TBI + Mel5 and TBI + Mel20. Brain injury was
induced by Marmarou method. Melatonin was injected i.p. at 1, 24, 48
and 72 h after brain trauma. Brain water and Evans blue dye contents
as well as oxidant factors were measured 72 h after TBI. ICP and
neurological scores were determined at -1, 1, 24, 48 and 72 h post-
TBI.

RESULTS: Brain water and Evans blue dye contents in melatonin-treated
groups decreased as compared to the TBI + vehicle group (p <0.001).
Veterinary coma scale (VCS) at 24, 48 and 72 h after TBI showed a
significant increase in melatonin groups (TBI + Mel5: p <0.01and TBI +
Mel20: p <0.001) in comparison to the TBI + vehicle group. ICP at 24,
48 and 72 h after TBI decreased in melatonin groups as compared to the
TBI + vehicle group (p <0.001). Superoxide dismutase and glutathione
peroxidase activities showed a significant increase, whereas
malondialdehyde level in these groups was significantly lower in
melatonin groups in comparison to the TBI + vehicle group (p <0.001).

CONCLUSION: Melatonin decreases brain edema, BBB permeability and ICP,
but increase VCS after TBI. These effects are probably due to
inhibition of oxidative stress.

Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

PMID:23608674

pii: S0188-4409(13)00079-9. doi: 10.1016/j.arcmed.2013.04.002.

---------------------

Metal chelating and hydrogen peroxide scavenging effects of
melatonin.
J Pineal Res. 2003 May;34(4):278-81.
Gulcin I, Buyukokuroglu ME, Kufrevioglu OI.
Department of Chemistry, Science and Arts Faculty,
Atatürk University, Erzurum, Turkey.
igul...@atauni.edu.tr

Antioxidant activity of a molecule is attributed to various
mechanisms such as prevention of chain initiation, binding of
transition
metal ion catalysts and decomposition of peroxides.
This study was aimed at evaluating the metal chelating and hydrogen
peroxide (H2O2) scavenging activity of melatonin.
The metal chelating and H2O2 scavenging activity increased with
increasing concentrations of melatonin (20-60 micro g/mL).
alpha-Tocopherol, butylated hydroxyanisole (BHA), and butylated
hydroxytoluene (BHT) were used as standards.
Sixty micrograms per milliliter concentration of melatonin exhibited
95% chelating effect on ferrous ions and scavenged 83% of H2O2.
On the other hand, the same concentration of alpha-tocopherol,
BHA, and BHT exhibited 58, 61, and 72% inhibition, respectively,
of the formation of the Fe2+-ferrozine complex and scavenged
48, 20, and 23%, respectively, of H2O2.
Based on these results, it is concluded that melatonin is an
effective metal chelating agent and scavenger of H2O2.
These properties may be major reasons for the melatonin's
ability to inhibit lipid peroxidation.

PMID: 12662350

---------------------

"A likely mechanism of seizure development post-TBI is
decompartmentalization of iron from extravasated hemoglobin (Hb)"

Lipoic acid pretreatment attenuates ferric chloride-induced seizures
in the
rat.
Brain Res. 2004 Aug 6;1016(2):139-44.
Meyerhoff JL, Lee JK, Rittase BW, Tsang AY, Yourick DL.
Division of Neuroscience, Walter Reed Army Institute of Research, 503
Robert
Grant Ave., Silver Spring, MD 20910-7500, USA.
james.meyerh...@na.amedd.army.mil

Traumatic brain injury (TBI) is often complicated by the occurrence
of
seizures, which adversely affect clinical outcome. The risk of
seizures
increases to the extent that the injury is associated with sub-
arachnoid
hemorrhage and hematoma. A likely mechanism of seizure development
post-TBI is
decompartmentalization of iron from extravasated hemoglobin (Hb). It
is well
known that iron can catalyze formation of reactive oxygen species
(ROS). Based
on this proposed mechanism, a descriptive model of TBI-induced
seizures, using
intracortical injection of iron salts, was developed by Willmore. We
have added
modifications to enhance the quantifiability of seizure activity and
have used
the model to examine the therapeutic efficacy of lipoic acids (ROS-
scavenging
antioxidants). Male SD rats were pretreated with alpha-lipoic acid
(ALA) and
dihydrolipoic acid (DHLA) or appropriate vehicles. Under anesthesia,
unilateral
intracortical infusions of ferric chloride were performed
stereotaxically. EEG
was recorded via extradural electrodes. EEG was sampled for 10 s of
every 60-s
interval over a 24-h period following injection of ferric chloride. We
measured
the number of seconds of epileptiform discharges or seizure activity
in every
10-s EEG sample during the 24 h. The EEGs of rats pretreated with ALA
and
DHLA exhibited 55% less seizure activity than vehicle-treated ferric
chloride-injected animals, suggesting that lipoic acids may be of use
in
preventing or attenuating TBI-induced seizures.


PMID: 15246849

Who loves ya.
Tom


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http://tinyurl.com/2r2nkh


Man Is A Herbivore!
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DEAD PEOPLE WALKING
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[John H. Gohde]

The probability of a physician administering Melatonin to a brain
injured patient is extremely remote.

When your brain is fucked, you are pretty much screwed. When you go
to conventional medicine for help you can kiss your life goodbye.

You're Science Bull, ain't fooling no one.

[ironjustice]

On Apr 26, 3:48 am, "John H. Gohde" <john.h.go...@gmail.com>
wrote:You're Science Bull, ain't fooling no one. <<

The "science bull" explains how , being physically prepared
beforehand , IE: lipoic acid , and also , administration of an iron
chelator , melatonin , after the fact , BOTH reduce the damage after a
TBI. One could conclude , if one is presented with a TBI , spilled
iron , a person could prepare for a TBI , much like lab techs who are
told to supplement lecithin / phosphatidylcholine to prepare , in the
possibility of meningitis passing to them during their lab work.

Who loves ya.
Tom

Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

> You're Science Bull, ain't fooling no one.- Hide quoted text -
>
> - Show quoted text -

[John H. Gohde]

On Apr 26, 7:50 pm, ironjustice <ironjust...@rock.com> wrote:
> On Apr 26, 3:48 am, "John H. Gohde" <john.h.go...@gmail.com>
> wrote:You're Science Bull, ain't fooling no one. <<
>
> The "science bull" explains how , being physically prepared
> beforehand  , IE: lipoic acid , and also , administration of an iron
> chelator , melatonin , after the fact , BOTH reduce the damage after a
> TBI. One could conclude , if one is presented with a TBI , spilled
> iron , a person could prepare for a TBI , much like lab techs who are
> told to supplement lecithin / phosphatidylcholine to prepare , in the
> possibility of meningitis passing to them during their lab work.

Bull!

Sorry, but unlike YOU, I intend to avoid TBI as much as possible.

YES, I try to avoid all sources of iron as much as possible,
especially the Science Bull contained in posts from ironjustice.

[ironjustice]

On Apr 26, 4:50 pm, ironjustice <ironjust...@rock.com> wrote: being
physically prepared beforehand <<

"Alpha-linolenic acid could be of therapeutic value against focal
ischemia/reperfusion injury to the brain"

Alpha-linolenic acid and riluzole treatment confer cerebral protection
and improve survival after focal brain ischemia.
Heurteaux C, Laigle C, Blondeau N, Jarretou G, Lazdunski M.
Neuroscience. 2006;137(1):241-51. Epub 2005 Nov 14.
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097, CNRS
Université de Nice Sophia Antipolis, Institut Paul Hamel, 660 Route
des Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
heur...@ipmc.cnrs.fr

Abstract
We investigated here the effects of alpha-linolenic acid and riluzole,
both activators of the 2P-domain K+ channel family TREK/TRAAK, in a
model of focal ischemia clinically relevant to stroke, not only
assessing neuronal protection, but also long term survival.
Moreover, all the drug treatments were initiated post-ischemia. Mice
were subjected to transient middle cerebral artery occlusion (1 h) and
reperfusion according to the intraluminal filament model.
Drugs were injected into the jugular vein according to three
protocols:
(i) a single dose of 4 mg/kg riluzole or 500 nmol/kg alpha-linolenic
acid at different reperfusion time;
(ii) a three-day therapy (a single dose of 2 mg/kg riluzole and 250
nmol/kg alpha-linolenic acid given 1-2, 48 and 72 h after
reperfusion);
(iii) a three-week therapy (a single dose of 2 mg/kg riluzole and 250
nmol/kg alpha-linolenic acid given once a week during three weeks
after reperfusion.
A combined treatment with 2mg/kg riluzole+250 nmol/kg alpha-linolenic
acid injected 2 h after reperfusion was also tested.
A single dose of riluzole (4 mg/kg) or alpha-linolenic acid (500 nmol/
kg) injected up to 3 h after reperfusion reduced drastically the
stroke volume by 75% and 86%, respectively.
Neurological deficits 24 h after ischemia were significantly improved
by alpha-linolenic acid500 or riluzole4 with a neurological score of
1.8 as compared with 2.5 observed in vehicle-treated mice.
Alpha-linolenic acid- and riluzole treatment were associated with a
reduction in cytopathological features of cell injury, including DNA
fragmentation and Bax expression in the cortex and the caudate
putamen.
With regard to the survival rate at 30 days, the best protections were
obtained with the alpha-linolenic acid-injection in the three-week
therapy as well as with a single dose of the combined treatment (2 mg/
kg riluzole+250 nmol/kg alpha-linolenic acid).
Palmitic acid, a saturated fatty acid that does not activate the 2P-
domain K-channel TREK/TRAAK family, did not provide any
neuroprotection.
Taken together, these data suggest that the TREK/TRAAK K-channel
family may be a promising target for neuroprotection, and that
riluzole and alpha-linolenic acid could be of therapeutic value
against focal ischemia/reperfusion injury to the brain.

PMID:16289892

Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk



> On Apr 26, 3:48 am, "John H. Gohde" <john.h.go...@gmail.com>
> wrote:You're Science Bull, ain't fooling no one. <<
>
> The "science bull" explains how , being physically prepared
> beforehand  , IE: lipoic acid , and also , administration of an iron
> chelator , melatonin , after the fact , BOTH reduce the damage after a
> TBI. One could conclude , if one is presented with a TBI , spilled
> iron , a person could prepare for a TBI , much like lab techs who are
> told to supplement lecithin / phosphatidylcholine to prepare , in the
> possibility of meningitis passing to them during their lab work.
>
> Who loves ya.
> Tom
>

> > - Show quoted text -- Hide quoted text -