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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Diindolylmethane Ameliorates Ischemic Stroke-Induced Brain Injury by Peripheral and Central Mechanisms

Author(s): Kakarla Ramakrishna, Sushil Kumar Singh and Sairam Krishnamurthy*

Volume 19, Issue 5, 2022

Published on: 28 November, 2022

Page: [462 - 475] Pages: 14

DOI: 10.2174/1567202620666221116161128

Price: $65

Abstract

Introduction: Diindolylmethane (DIM), a major acid condensation product of Indole-3- carbinol, is known to inhibit platelet aggregation and thrombosis. The drugs with antiplatelet and antithrombotic activities are used to treat ischemic stroke.

Objective: The present study investigated the role of DIM on platelet aggregation inhibitory properties in middle cerebral artery occluded (MCAO) rats.

Methods: DIM (12.5, 25, and 50 mg/kg) was orally administered to MCAO rats for 3 days. Platelet aggregation, platelet cyclic adenosine monophosphate (cAMP), reactive oxygen species (ROS), hydrogen peroxide (H2O2), and serum cyclooxygenase (COX-1), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2), and inflammatory markers were estimated. Further brain structural and functional recovery was evaluated by measuring cerebral blood flow, neurological deficits, brain infarction, blood-brain barrier (BBB) leakage, brain water content, and histological abnormalities.

Results: DIM significantly ameliorated adenosine diphosphate (ADP), collagen, thrombin, and arachidonic acid-induced platelet aggregation by inhibiting COX-1, TXB2, and PGE2 and elevating cAMP. Further, DIM also alleviated platelet-mediated oxidative stress (ROS and H2O2) and reduced the serum inflammatory markers, tumor necrosis factor-α (TNF-α) and interleukin -6 (IL-6), and increased anti-inflammatory cytokine, IL-10, in MCAO rats.

Conclusion: DIM treatment confers neuroprotection in MCAO rats by inhibition of platelet aggregation, platelet-mediated oxidative stress, and inflammation. Correspondingly, DIM improved cerebral blood flow and reduced neurological deficits, brain infarction, BBB leakage, brain water content, and histopathological abnormalities indicating the preservation of brain structural integrity. Thus, the present study provided preclinical evidence of DIM neuroprotection against ischemic stroke.

Keywords: Diindolylmethane, MCAO, platelet aggregation, inflammation, brain infarction, neuroprotection.

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