, hypothermia, brain inflammation and antiiflammatories

[Guest guest]

Hi Sara, just came across this and thought it was interesting as it talks about increased COX-2 (proinflammatory molecule) expression in ischemic brain damage and neuroinflammation (present in autism), and how decreasing temperature and lowering COX-2 (which is what ibuprofen does!) resulted in protection of mice brains... rofecoxib is no longer on the market, interestingly it was investigated for use in Alzheimers... I am putting together a list of natural antiinflammatories that work on the same pathways as Ibuprofen - reducing cox-2 and prostaglandins, hopefully some of them could have the same effects for our kids... That is of course if the good things with ibuprofen are not simply due to removal of some chronic pain in them!!Curr Neurovasc Res. 2007 Nov;4(4):274-9.Increased

neuronal injury in transgenic mice with neuronal overexpression of

human cyclooxygenase-2 is reversed by hypothermia and rofecoxib

treatment.Xiang Z, ... Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.Cyclooxygenase-2

(COX-2) is up-regulated during ischemia. However, the role of COX-2 in

neuronal injury is still unclear. In this study we tested whether

neuronal overexpression of human COX-2 in a transgenic mouse model

potentiates neuronal injury after global ischemic insult. Further, we

tested whether the neuronal injury could be ameliorated by

intra-ischemic mild hypothermia (33-34 degrees C) alone or in

combination with diet treatment of rofecoxib, a COX-2 specific

inhibitor. Global ischemia with intra-ischemic normothermia (36-37

degrees C) resulted in significantly higher neuronal damage in the CA1

region of hippocampus of transgenic mice than in wild type controls,

confirming a deleterious role of COX-2 in ischemic neuronal damage.

Hypothermia significantly reduced neuronal damage in both transgenic

mice and wild type controls to the same extent, suggesting that the

aggravating effect of COX-2 could be largely eliminated by hypothermia.

When hypothermia was combined with rofecoxib treatment, neuronal damage

was further reduced in response to global ischemia. The results suggest

that COX-2 inhibition by prophylactic treatment with rofecoxib coupled

with hypothermia at the time of acute stroke insult could be an

effective therapeutic approach in early stages of stroke treatment in

high risk patients.PMID: 18045153 [PubMed - indexed for MEDLINE]

[Guest guest]

Wow,

thanks very much for that, Natasa. Sara x

-----Original

Message-----

From:

Autism-Biomedical-Europe

[mailto:Autism-Biomedical-Europe ] On Behalf Of natasa778

Sent: 10

February 2008

22:17

To:

Autism-Biomedical-Europe

Subject:

, hypothermia, brain inflammation and

antiiflammatories

Hi Sara, just came across this and thought it was interesting as it

talks about increased COX-2 (proinflammatory molecule) expression in ischemic

brain damage and neuroinflammation (present in autism), and how decreasing

temperature and lowering COX-2 (which is what ibuprofen does!) resulted

in protection of mice brains...

rofecoxib is no longer on the market, interestingly it was investigated for use

in Alzheimers...

I am putting together a list of natural antiinflammatories that work on the

same pathways as Ibuprofen - reducing cox-2 and prostaglandins, hopefully some

of them could have the same effects for our kids... That is of course if

the good things with ibuprofen are not simply due to removal of some chronic

pain in them!!

Curr Neurovasc Res. 2007 Nov;4(4):274-9.

Increased neuronal injury in transgenic mice with

neuronal overexpression of human cyclooxygenase-2 is reversed by

hypothermia and rofecoxib treatment.

Xiang Z, ... Department of Psychiatry, Mount Sinai School of Medicine,

New York, NY 10029, USA.

Cyclooxygenase-2 (COX-2) is up-regulated during

ischemia. However, the role of COX-2 in neuronal injury is still unclear. In

this study we tested whether neuronal overexpression

of human COX-2 in a transgenic mouse model potentiates neuronal injury

after global ischemic insult. Further, we tested whether the neuronal injury

could be ameliorated by intra-ischemic mild hypothermia (33-34 degrees C) alone

or in combination with diet treatment of rofecoxib, a COX-2 specific inhibitor.

Global ischemia with intra-ischemic normothermia (36-37 degrees C) resulted in

significantly higher neuronal damage in the CA1 region of hippocampus of

transgenic mice than in wild type controls, confirming a deleterious role of

COX-2 in ischemic neuronal damage. Hypothermia

significantly reduced neuronal damage in both transgenic mice

and wild type controls to the same extent, suggesting that the aggravating

effect of COX-2 could be largely eliminated by hypothermia. When hypothermia was combined with rofecoxib

treatment, neuronal damage was further reduced in response to

global ischemia. The results suggest that COX-2 inhibition by prophylactic

treatment with rofecoxib coupled with hypothermia at the time of acute stroke

insult could be an effective therapeutic approach in early stages of stroke

treatment in high risk patients.

PMID: 18045153 [PubMed - indexed for MEDLINE]