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Related Concept Videos

Ischemic Stroke l: Introduction01:15

Ischemic Stroke l: Introduction

Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...

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A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
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Network-based drug repurposing for potential stroke therapy.

Qihui Wu1,2,3, Cuilan Chen4, Weihua Liu2

  • 1Clinical Research Center, Hainan Provincial Hospital of Traditional Chinese Medicine, Hainan Medical University, Haikou 571000, China.

Computational and Structural Biotechnology Journal
|May 19, 2023
PubMed
Summary
This summary is machine-generated.

Drug repurposing identified 185 potential stroke drug candidates using a network approach. Six drugs, including cinnarizine and phenelzine, showed anti-stroke effects by reducing inflammation markers like IL-6 and COX-2.

Keywords:
Approved drugsIn vitro experimental validationNetwork-based drug repurposingStroke

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Computational Biology

Background:

  • Stroke is a leading global cause of death and disability with limited therapeutic options.
  • Drug repurposing offers a cost-effective and time-efficient strategy for identifying new stroke treatments.
  • Existing therapies for stroke are insufficient, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To computationally identify potential drug candidates for stroke by repurposing approved drugs from the DrugBank database.
  • To validate the efficacy of identified drug candidates through experimental testing.
  • To elucidate the anti-stroke mechanisms of promising drug candidates.

Main Methods:

  • Development of a drug-target network for approved drugs.
  • Application of a network-based approach for drug repurposing to identify stroke candidates.
  • Experimental validation of drug candidates using oxygen-glucose deprivation/reoxygenation (OGD/R) induced BV2 cell models.
  • Mechanism of action studies using Western blot and Olink inflammation panels.

Main Results:

  • Identified 185 potential drug candidates for stroke through computational repurposing.
  • Validated 36.8% (68 out of 185) of candidates with existing literature supporting therapeutic effects on stroke.
  • Six selected drugs, including cinnarizine and phenelzine, demonstrated significant anti-stroke activity in OGD/R induced BV2 cells.
  • Cinnarizine and phenelzine were found to exert anti-stroke effects by inhibiting Interleukin-6 (IL-6) and Cyclooxygenase-2 (COX-2) expression.

Conclusions:

  • The study presents an efficient network-based methodology for *in silico* identification of stroke drug candidates.
  • Drug repurposing via network analysis is a viable strategy for discovering novel stroke therapeutics.
  • Cinnarizine and phenelzine show promise as potential anti-stroke agents with specific anti-inflammatory mechanisms.