Abstract: synthase, statins have been contemplated in

Abstract:

Treatment with
statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) decreases the
risk of ischemic stroke between patients with increased risk of vascular disease.
Current experimental abstracts point to neuroprotective properties of statins
in acute cerebral ischemia. There is an established fact in between
bioavailability of nitric oxide and the activity of statins and  ischemic stroke. On account of their
capability to up-regulate nitric oxide synthase, statins have been contemplated
in the therapy of a number of the central nervous system disorders, including
cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, tumors, and
trauma. It has been asserted that they restrain inflammatory response and
secondary injury after acute ischemia.

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Key
words:

statins, Alzheimer’s disease, stroke,
multiple sclerosis, neuroprotection

 

INTRODUCTION

Statins
have, at present, the promising ability to accommodate a new therapeutic goal
for multitudinal neurological diseases. It is well full-fledged that statins
decrease cholesterol levels and anticipate coronary heart disease. Moreover,
attestations proposed that statins have supplementary possessions such as
endothelial protection via action on the nitric oxide synthase system in
addition to antioxidant, anti-inflammatory and anti-platelet effects. These possessions
might have potential therapeutic association not only in stroke but also in neurological
disorders such as Alzheimer disease, Parkinson’s disease, multiple sclerosis
and primary brain tumors. The
principal mechanism of action of statins is based on the inhibition of
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus the
restriction of the enzyme in the biosynthesis of cholesterol. That results in
the growth in a number and activity of low density lipoprotein (LDL) receptors,
and decrease in this cholesterol fraction in the plasma as a consequence 1

 

Apart from cholesterol-dependent
mechanisms of action, statins also precisely up-regulate endothelial nitric oxide
synthase (eNOS, also titiled NOS3 or NOS III) expression, independent of
cholesterol levels 2, 3.

 

 

STATINS
AND STROKE

 

Statins decreases strokes
of various etiology by a array of mechanisms, containing modulation of
precerebral atherothrombosis in the aorta and the carotid artery and therefore
anticipating plaque division and artery-toartery thromboembolism by restricting
coagulation at its various levels, degenerating tissue factor, innovation of
prothrombin to thrombin activity 4.

 

Vaughan et al. 5
have shown in experimental models of ischemic stroke that statin therapy decreases
the size of brain infarct and ameliorate neurologic after effect by direct
up-regulation of brain endothelial NO synthase. Additional to that, the
anti-inflammatory actions of statins probably contribute to neuroprotection and
stroke prevention.

 

The Pravastatin
Lipids and Atherosclerosis in the Carotids II (PLACII) study also established a
cognent decline in carotid intimal-medial thickness in pravastatin-treated
patients. The impact of statin treatment on aortic atherosclerosis has not been
broadly analysed 5. Decrease in stroke incidence by statins like pravastatin,
simvastatin 6 and lovastatin were also accustomed in short-term clinical
studies 7.

 

In the experiment
conducted by The Large Prospective Studies Collaboration Group, there was no correlation
between cholesterol and stroke. However, they did not categorize between
ischemic and hemorrhagic stroke 8. Cucchiara et al. 8 have shown that the
opposing effects of cholesterol on ischemic versus hemorrhagic stroke risk may
confuse efforts to compare cholesterol levels with stroke except stroke type (
i.e. hemorrhagic vs. ischemic) is taken into account.

 

In the Cholesterol
and Recurrent Events (CARE) Trial, the pravastatin group had a 31% lower
incidenceof all strokes, even though again the incidence of lethal strokes was
about the same. Summarizing, there was no increase in the rate of hemorrhagic
stroke 9.

 

On Comparisons of
statins, Laufs et al. 10 have showed the results that eshtablish that
rosuvastatin is at least as effective as simvastatin and atorvastatin and
provided better protection than lovastatin and mevastatin in the mouse middle
cerebral artery (MCA) stroke model.

 

STATINS AND AZD

 

In 2013, as many as 5
million Americans were living with Alzheimer’s disease 11. By 2050, this
number is calculated to reach to 14 million, a almost three-fold increase 11.
Increased lev­els of ?-amyloid and apolipoprotein E have been found to be
affliated with AD 12-14. Inclusion to that, atherosclerosis and elevated
levels of plasma total cholesterol or triglyceride and low-density lipoprotein
cholesterol (LDL-C) exasperated the symptoms of AD.

 

According
to a current study, Alzheimer’s is evoked by a lower intake in omega-3 fatty acids,
found in fish 15. The study farther explicated that cholesterol esters are a
common pool for fatty acids in plasma. Inpoint of fact, it is found that there
are considerably lower numbers of fatty acids, phospholipids and esterified cholesterol
in the CSF of accustomed Alzheimer’s subjects 16.

 

Dr. Seneff also
asserted that lower levels of fatty acids are found in the CSF in patients with
Alzheimer’s. In point of fact, it was bring into being that about Alzheimer’s
patients have less that 20% of the concentration of fatty acids in CSF compared
to non-Alzheimer’s patients 17. Taling into account
that statins can additionally reduce this number by lowering the carry capacity
of fats by cholesterol, it should be made alert that statins can possibly pose
a threat to provoking Alzheimer’s rather than preventing it.

 

Follow-up studies
in humans have currently suggested that patients getting statin therapy have a
reduced incidence of dementia. Cholesterol lowering with statins may have
potential therapeutic benefit in AD. Simvastatin has been shown to decrease plasma
levels of apoE in patients with senile AD, though cerebrospinal fluid levels of
apoE were not significantly replaced18,19.