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NATIONAL SCIENCE DAY
JACOB INSTITUTE OF BIOMEDICAL AND BIOENGINEERING
SAM HIGGINBOTTOM UNIVERSITY OF AGRICULTURE,
TECHNOLOGY & SCIENCES
NEUROPROTECTION
AGAINST CEREBRAL
ISCHEMIA
MAULSHREE
18MSCBT002
M.SC. BIOTECHNOLOGY
MCE-JIBB
SHUATS
KNOWING STROKE
 A stroke or cerebrovascular accident is a serious and fatal medical condition that occur
when the blood supply to part of the brain is severely reduced or cut off, depriving brain
tissues of oxygen and nutrients.
 The part of the affected brain dies and can no longer function.
 The dead area that results from stroke is known as an infarct. Without prompt medical
treatment, the area of brain cells surrounding the infarct will also die.
 Worldwide, stroke is the commonest cause of mortality after coronary artery disease. The
lifetime risk of stroke after 55 years of age is 1 in 5 for women and 1 in 6 for men.
 The crude prevalence of stroke ranged from 44.29 to 559/100,000 persons in different parts
of the country during the past decade. These values were higher than those of high-income
countries.
 This indicated a 26 per cent increase in global stroke deaths during the past two decades.
RISK FACTORS
• Most stroke risk factors are lifestyle related,
so everyone has the power to reduce their
risk of having a stroke.
• Risk factors should be considered together
to understand the overall risk of stroke.
• Some stroke risk factors, such as gender,
age and family history, can’t be controlled.
• Lifestyle factors that increase your risk of
stroke include high blood pressure,
smoking, diabetes, high blood cholesterol
levels, heavy drinking, high salt and high fat
diet and lack of exercise.
• Someone who has already experienced a
stroke is at increased risk of having another
TYPES OF STROKE
MECHANISMS OF ISCHEMIC CELL INJURY AND DEATH
EMERGRNCY TREATMENTS FOR STROKE
• Emergency treatment with medications. Therapy with clot-busting drugs must start.
Intravenous injection of tissue plasminogen activator (tPA). Also called alteplase, is considered the
gold standard treatment for ischemic stroke. An injection of tPA is usually given through a vein in
the arm. This potent clot-busting drug ideally is given within three hours.
Like tPA, Pifithrin-α (PFTα) was discovered as a specific inhibitor of signaling by the tumor
suppressor protein p53.
• Emergency endovascular procedures. Procedures performed directly inside the blocked blood
vessel.
Medications delivered directly to the brain. A long, thin tube (catheter)are inserted through an
artery.
Removing the clot with a stent retriever. For larger clots.
• There are other methods also like surgical clipping, coiling, etc.
• Warfrin ( anti-platelet drug) for hemorrhagic stroke.
NEUROPROTECTION
• Despite advances in treatment and after decades of research , there is still
little that can be done to prevent stroke-related brain damage.
• The concept of neuroprotection is a source of considerable interest in order to
establish novel therapies.
• P53 is a promising target for stroke therapy, as it is rapidly upregulated in
ischemic brain tissue where it initiates apoptosis.
• Neuroprotection often deals with finding suitable compounds that have the
ability to inhibit molecular mediators of cell death pathway.
PHYTOCHEMICALS AS NEUROPROTACTANTS
• Phytochemicals are widely explored for there therapeutic potentials.
• Emerging findings suggest that extracts of the Indian ayurvedic herb Withania
somnifera have the ability to target multiple pathophysiological processes
involved in stroke including oxidative stress, inflammation and apoptotic cell
death.
• Many phytochemicals compounds of this plant have been reported to show
inhibitory effects against ischemic cascade.
• As to structure-based drug design, molecular docking is the most commonly
used method.
• There are many compounds, but molecular docking of some screened ligands
and pifithrin ( reported inhibitor ) against p53 protein was performed by
Autodock software tool.
• It helps to identify or find out the best matching between the ligands and the
macromolecules & also to find out which of the ligand has the lowest binding
energy and has more hydrogen bonding with the receptor.
• Withaferin A and Withanolide A are a better inhibitor of p53-mediated apoptosis
than pifithrin and can be treated as future neuroprotectant .
• It can be developed into therapeutic drug for treating cerebral ischemia.
• These therapeutic drugs can be studied by carrying out molecular biology
experimentations in animal model of cerebral ischemia.
SCIENCE FOR THE
PEOPLE AND PEOPLE FOR
THE SCIENCE.
BIOTECHNOLOGY IS
EVERYWHERE.
MEDICINE AND DRUG
DESIGNING

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Neuroprotection against cerebral ischemia

  • 1. NATIONAL SCIENCE DAY JACOB INSTITUTE OF BIOMEDICAL AND BIOENGINEERING SAM HIGGINBOTTOM UNIVERSITY OF AGRICULTURE, TECHNOLOGY & SCIENCES
  • 3. KNOWING STROKE  A stroke or cerebrovascular accident is a serious and fatal medical condition that occur when the blood supply to part of the brain is severely reduced or cut off, depriving brain tissues of oxygen and nutrients.  The part of the affected brain dies and can no longer function.  The dead area that results from stroke is known as an infarct. Without prompt medical treatment, the area of brain cells surrounding the infarct will also die.  Worldwide, stroke is the commonest cause of mortality after coronary artery disease. The lifetime risk of stroke after 55 years of age is 1 in 5 for women and 1 in 6 for men.  The crude prevalence of stroke ranged from 44.29 to 559/100,000 persons in different parts of the country during the past decade. These values were higher than those of high-income countries.  This indicated a 26 per cent increase in global stroke deaths during the past two decades.
  • 4. RISK FACTORS • Most stroke risk factors are lifestyle related, so everyone has the power to reduce their risk of having a stroke. • Risk factors should be considered together to understand the overall risk of stroke. • Some stroke risk factors, such as gender, age and family history, can’t be controlled. • Lifestyle factors that increase your risk of stroke include high blood pressure, smoking, diabetes, high blood cholesterol levels, heavy drinking, high salt and high fat diet and lack of exercise. • Someone who has already experienced a stroke is at increased risk of having another
  • 6. MECHANISMS OF ISCHEMIC CELL INJURY AND DEATH
  • 7.
  • 8. EMERGRNCY TREATMENTS FOR STROKE • Emergency treatment with medications. Therapy with clot-busting drugs must start. Intravenous injection of tissue plasminogen activator (tPA). Also called alteplase, is considered the gold standard treatment for ischemic stroke. An injection of tPA is usually given through a vein in the arm. This potent clot-busting drug ideally is given within three hours. Like tPA, Pifithrin-α (PFTα) was discovered as a specific inhibitor of signaling by the tumor suppressor protein p53. • Emergency endovascular procedures. Procedures performed directly inside the blocked blood vessel. Medications delivered directly to the brain. A long, thin tube (catheter)are inserted through an artery. Removing the clot with a stent retriever. For larger clots. • There are other methods also like surgical clipping, coiling, etc. • Warfrin ( anti-platelet drug) for hemorrhagic stroke.
  • 9. NEUROPROTECTION • Despite advances in treatment and after decades of research , there is still little that can be done to prevent stroke-related brain damage. • The concept of neuroprotection is a source of considerable interest in order to establish novel therapies. • P53 is a promising target for stroke therapy, as it is rapidly upregulated in ischemic brain tissue where it initiates apoptosis. • Neuroprotection often deals with finding suitable compounds that have the ability to inhibit molecular mediators of cell death pathway.
  • 10. PHYTOCHEMICALS AS NEUROPROTACTANTS • Phytochemicals are widely explored for there therapeutic potentials. • Emerging findings suggest that extracts of the Indian ayurvedic herb Withania somnifera have the ability to target multiple pathophysiological processes involved in stroke including oxidative stress, inflammation and apoptotic cell death. • Many phytochemicals compounds of this plant have been reported to show inhibitory effects against ischemic cascade. • As to structure-based drug design, molecular docking is the most commonly used method.
  • 11. • There are many compounds, but molecular docking of some screened ligands and pifithrin ( reported inhibitor ) against p53 protein was performed by Autodock software tool. • It helps to identify or find out the best matching between the ligands and the macromolecules & also to find out which of the ligand has the lowest binding energy and has more hydrogen bonding with the receptor. • Withaferin A and Withanolide A are a better inhibitor of p53-mediated apoptosis than pifithrin and can be treated as future neuroprotectant . • It can be developed into therapeutic drug for treating cerebral ischemia. • These therapeutic drugs can be studied by carrying out molecular biology experimentations in animal model of cerebral ischemia.
  • 12. SCIENCE FOR THE PEOPLE AND PEOPLE FOR THE SCIENCE. BIOTECHNOLOGY IS EVERYWHERE. MEDICINE AND DRUG DESIGNING