Magnesium sulphate & Sodium sulphate prevent Brain Damage following Stroke

[Guest guest]

The cerebrovascular disease research group's main objective is to increase our

understanding of the mechanisms involved in neuronal death (brain damage)

following stroke/cerebral ischaemia, in order to develop treatments to reduce

damage.

 

http://www.cnnd.uwa.edu.au/teams/teamcvdl/cvdl.htm

 

Stroke occurs when there is a reduced blood supply to the brain, resulting in a

lack of oxygen and nutrients to neurons.

 

Stroke can occur when there is a reduced blood supply to the entire brain (eg.

cardiac arrest, heart bypass surgery, subarachnoid haemorrhage, closed head

injury, perinatal hypoxia) or when there is a reduced blood supply to a specific

region of the brain, usually as a result of a blockage in brain artery

(thrombo-embolic stroke).

 

The brain damage following a stroke can result in death, coma or more commonly

neurological deficits that affect speech, vision, memory, coordination and

movement. There is no totally effective treatment to prevent the brain damage

and subsequent neurological deficits that occur following stroke.

 

In Australia and all western countries stroke is the third most common cause of

death and the single leading cause of disability. Stroke affects 55,000 - 65,000

Australians every year. Approximately 40,000 people suffer a thrombo-embolic

stroke and 1,500 a subarachnoid haemorrhage.

 

Head injury resulting in an estimated 10,000 - 20,000 people suffering moderate

to severe brain damage annually, is the leading cause of death and disability in

Australians under the age of fifty. Based on figures from the United States a

further 2,000 - 3,000 Australians suffer some form of brain damage associated

with cardiac arrest and cardiac bypass surgery each year. Two - four full-term

newborn infants suffer asphyxia/hypoxia at or shortly before birth. The

estimated direct and indirect cost of stroke to the Australian community is over

2 billion dollars annually.

 

Currently, available treatment options for inhibiting neuronal death following

stroke, have serious clinical limitations since they need to be administered

within minutes, to a few hours, after the stroke has occurred.

 

Due to the inevitable delays in obtaining medical attention, few patients

receive these treatments early enough to be effective. A large proportion of the

neuronal death that occurs following a stroke develops over many hours to a few

days, which unfortunately can not be inhibited by available drugs. However,

since the neuronal death is delayed, it may provide a wider therapeutic window

which would allow drugs to be administered several hours after the stroke.

 

The exact mechanisms leading to delayed neuronal death are unknown. Therefore,

understanding the cellular and molecular mechanisms involved in delayed neuronal

death will enable a more rational approach for developing drugs to inhibit

neuronal loss following stroke and hence improve patient outcome.

 

To study neuronal death we are using in vivo and in vitro models of stroke. We

use two in vivo rodent models of stroke. In the global model we induce stroke by

reducing blood supply to the entire brain, which results in a uniform and

consistent neuronal loss to a specific region in the brain. The focal model we

induce stroke by reducing blood supply to localised area in the brain, which

results in neuronal loss to that region. In our in vitro model of stroke, we

culture neurons and incubate them in medium deficient in oxygen and other

nutrients in order to mimic conditions that occur during stroke in vivo.

 

 

 

Magnesium sulphate and sodium sulphate can prevent brain damage following stroke

 

Recent work in our laboratory by Dr Andrew Miles using our in vivo global model

of stroke has demonstrated that there is an optimal dose of magnesium sulphate

that provides maximum protection against stroke. Low and high doses of magnesium

sulphate provide no or little protection against brain damage following stroke.

Dr Miles also showed that magnesium sulphate when administered up to 24 hours

following a stroke could prevent brain damage in rats. A surprising and novel

finding from this work was showing that sodium sulphate could also prevent brain

damage following stroke. To our knowledge, no previous study has shown or

considered a potential neuroprotective role for sulphate.

 

The neuroprotective action of magnesium in the global mode of stroke suggested

to us that magnesium sulphate and sodium sulphate could also prevent brain

damage associated with the more common form of stroke (thrombo-embolic stroke; Å

40,000 cases/year) which results from a blockage to a artery supplying blood to

a specific region of the brain. To evaluate the efficacy of magnesium sulphate

and sodium sulphate in preventing brain damage following thrombo-embolic stroke,

Dr Richard Stacey established the focal model of stroke in our laboratory. The

focal stroke experiments showed that magnesium sulphate or sodium sulphate could

reduce brain damage by 55 - 65%. We are currently determining if magnesium

sulphate or sodium sulphate can reduce brain damage when given many hours (4 - 8

hrs) after this form of stroke.

 

 

 

Investigating genes expressed in the brain following stroke in the rat

 

Genes are expressed by all cells and code for proteins that control many

cellular functions including cell division and maturation, biochemical pathways

and cell death. It has been shown that following stroke changes in the

expression of genes occurs in the brain, and by blocking new gene expression,

brain damage can be reduced. Identifying genes that are expressed in the brain

following stroke and responsible for neuronal death may provide therapeutic

targets to reduce brain damage. Ms Bernadette Majda has been investigating the

expression of genes in the brain following stroke (global) in our rat model.

Gene expression was examined 6 hours after stroke induction and 12 genes have

been isolated. Ten of the genes correspond known genes, while two genes appear

to be novel. Ms Majda and Dr Stacey have also shown that two of these genes,

heat shock protein 86 and one of the novel genes are also expressed following

focal cerebral ischaemia.

 

Further characterisation of genes expressed following stroke will determine if

genes expressed following global cerebral ischaemia are expressed following

focal ischaemia. The time course of gene expression will be determined and the

cell type(s) expressing genes in the brain identified.

 

Characterisation of novel gene(s) will involve isolating and sequencing the

full-length gene and determine its expression profile in other tissues.

 

 

 

Investigation of the role of genes in neuronal survival using our in vitro model

of stroke

 

The role of these genes in neuronal death will be evaluated using our in vitro

model of stroke. This will involve blocking the expression of the gene in

neurons and subjected the neurons to stroke-like conditions. If neuronal cell

death is reduced by the inhibition of the gene this is strong evidence that the

gene is involved in promoting brain damage following stroke. We are currently

determining if genes expressed during cerebral ischaemia/stroke are expressed in

our in vitro model of simulated ischaemia/stroke.

 

 

 

Investigation of the role of TNF in neuronal death using our in vitro model of

stroke

 

Nick Williamson investigated the role of tumour necrosis factor alpha (TNF) in

neuronal death following in vitro ischaemia/stroke. It is not known if TNF,

which is increased following cerebral ischaemia, is neurotoxic or

neuroprotective during ischaemia. In addition, little is known about the

differential role that the two different TNF receptors play in neuronal

death/survival following stroke.

 

Mr Williamson showed that TNF has no detrimental effects on normal neurons and

can protect neurons when present in neuronal cultures during in vitro ischaemia.

In contrast, it was found that TNF provides no neuroprotection when present in

neuronal cultures before or after ischaemia only. Similar results were obtained

with TNF when neuronal cultures were subjected to the ischaemia-like insults of

glucose deprivation and glutamate cytotoxicity. These results suggest that

neuroprotection in the presence of TNF is mediated via post-translational (gene

expression independent) changes occurring within neurons induced by constant TNF

receptor activation. Once TNFs removed, neuroprotection is lost. We have also

detected TNF receptor upregulation after in vitro ischaemia using

immunocytochemistry.

 

 

 

Awards and Achievements

 

Dr Richard Stacey; Student prize, 20th Symposium of West Australian

Neuroscience, 1999.

 

Mr Neville Knuckey, awarded Doctorate of Medicine, University of Western

Australia, 1999.

 

Mr Neville Knuckey awarded by the University of Western Australia the title of

Clinical Associate Professor.

 

Mr Nick Williamson, awarded Honours Degree (IIA), Murdoch University, 1999.

_________________

JoAnn Guest

mrsjoguest

DietaryTipsForHBP

http://www.geocities.com/mrsjoguest

 

 

 

 

 

 

 

The complete " Whole Body " Health line consists of the " AIM GARDEN TRIO "

Ask About Health Professional Support Series: AIM Barleygreen

 

" Wisdom of the Past, Food of the Future "

 

http://www.geocities.com/mrsjoguest/AIM.html

 

PLEASE READ THIS IMPORTANT DISCLAIMER

We have made every effort to ensure that the information included in these pages

is accurate. However, we make no guarantees nor can we assume any responsibility

for the accuracy, completeness, or usefulness of any information, product, or

process discussed.

 

 

 

 

 

 

 

 

 

Finance Tax Center - File online. File on time.