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VOL. 9, ISSUE 1 (2024)
Calcium signaling: A pharmacological approach in remote ischemic preconditioning against cerebral vascular dementia
Authors
Sandeep Goyal, Rakesh Chawla, Vijender Kumar, Payal Mittal, Mohd Hanifa
Abstract
Dementia is the world’s most prevalent neurodegenerative disease,
affecting over 50 million people worldwide and estimated to rise affect upto
152 million people by 2050. vascular dementia (VD) is the second most prominent
form of dementia. Vascular dementia (VD), in which cognitive decline is
attributed to some form of vascular injury, typically ischaemic, is the second
most common cause of dementia in Western societies. It is believed that
vascular dementia is a distinct clinical and pathological entity from
Alzheimer’s dementia, Lewy body dementia, or frontotemporal dementia, even if
aspects of vascular disease may be present in these conditions. Vascular
dementia is caused by ischaemic insults such as haemorrhage and hyperfusion
that trigger neurodegeneration by depriving nerve cells of oxygen and glucose.
There are two types of vascular dementia. Multi-infarct dementia (MID) and
small vessel dementia SVD). MID is considered the most common form of vascular
dementia (VD), a primary cause of dementia second to Alzheimer's disease (AD).
That is characterized by multiple lesions and infarction of small arteries in
the cerebral gray-white matter. SVD primarily distresses the small perforating
arteries, being defined as vessels with less than 50 µm diameters, also defined
as “all the vessels within the brain parenchyma plus the vessels with a
diameter less than 500 µm in the leptomeningeal space” supplying the deep brain
structures, general increased arterial stiffness is associated with an
increased white matter lesion burden. Ischemia/reperfusion (I/R, restoration of
blood flow) injury is a major consequence of cardiac arrest period and
resuscitation. However, short duration of cerebral ischemia (less than 10 min)
can lead to neuronal death within the brain especially in the hippocampus and
causes learning and memory deficits. Following I/R, there are three important
threats: excitotoxicity, oxidative/nitrosative stress and neuroinflammation.
Under normal physiological conditions, integrate neural signals, inhibit Ca2+-mediated
excitation, contribute to information processing, and structurally and
functionally bridge neurons and vascular endothelial cells. Incase of I/R
injury, due to oxidative stress and mitochondrial dysfunction, the calcium
influx increases and thereby calcium overload to activate the caspases and
downregulation of eNOS to produce endothelial dysfunction and vascular
dementia. Remote ischemic pre-conditioning (RIPC) work by reduced the oxidative
stress and regulating the various transduction pathways such as PI3K/Akt
pathway, PKC pathway, TLR- 4 pathway. The mechanism involves in
pre-conditioning also include inhibition of autophagy and apoptosis, improvement
of mitochondrial permeability transition, and attenuation of endoplasmic
reticulum stress and also the activation of opioid receptors prevent
endothelial dysfunction. Literature survey suggests the role of calcium
signalling in I/R, IPC and RIPC. NCX plays an important role in the maintenance
of Ca2+ homeostasis and is detected in the plasma membrane of most
cells, including neurons and glia. Na+/Ca2+ exchanger
(Sodium/calcium exchanger or NCX) by regulating the homeostasis of Na+
and Ca2+, plays a key role in the evolution of ischemic neuronal
damage. This review suggests that the pivotal role of NCX inhibition in
neuroprotection against cerebral ischemia reperfusion injury and thereby
vascular dementia.
Pages:15-21
How to cite this article:
Sandeep Goyal, Rakesh Chawla, Vijender Kumar, Payal Mittal, Mohd Hanifa "Calcium signaling: A pharmacological approach in remote ischemic preconditioning against cerebral vascular dementia". International Journal of Pharmaceutical Science and Research, Vol 9, Issue 1, 2024, Pages 15-21
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