Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study

Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute...

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Main Authors: Christiana Anastasiadou, Anastasios Papapetrou, George Galyfos, Kostas Vekrellis, Patroklos Katafygiotis, Andreas Lazaris, George Geroulakos, Angelos Megalopoulos, Christos Liapis, Nikolaos Kostomitsopoulos, John Kakisis
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Language:English
Published: MDPI AG 2025-04-01
Series:Neurology International
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Online Access:https://www.mdpi.com/2035-8377/17/5/69
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author Christiana Anastasiadou
Anastasios Papapetrou
George Galyfos
Kostas Vekrellis
Patroklos Katafygiotis
Andreas Lazaris
George Geroulakos
Angelos Megalopoulos
Christos Liapis
Nikolaos Kostomitsopoulos
John Kakisis
author_facet Christiana Anastasiadou
Anastasios Papapetrou
George Galyfos
Kostas Vekrellis
Patroklos Katafygiotis
Andreas Lazaris
George Geroulakos
Angelos Megalopoulos
Christos Liapis
Nikolaos Kostomitsopoulos
John Kakisis
author_sort Christiana Anastasiadou
collection DOAJ
description Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke. Materials and Methods: Twelve-week-old rats were randomly assigned to four groups, each containing six rats: a cilostazol group, an aspirin group, an aspirin plus cilostazol group, and a control group. Each substance was administered for four weeks. Permanent brain ischemia was induced over 2 h using intraluminal middle cerebral artery occlusion. A neurologic examination was conducted, followed by euthanasia and histological examination of the CA1 hippocampal region. The hematoxylin and eosin stain was used to assess the total number of intact neuronal cell bodies and pyknotic nuclei, an indicator of early irreversible neuronal injury. Results: In the ipsilateral hippocampus, monotherapy with either aspirin or cilostazol significantly reduced pyknotic nuclei compared with the control group (<i>p</i> = 0.0016 and <i>p</i> = 0.0165, respectively). However, combination therapy showed no significant difference from the controls (<i>p</i> = 0.2375). In the contralateral hippocampus, cilostazol monotherapy demonstrated significantly reduced pyknotic nuclei (<i>p</i> = 0.0098), whereas aspirin monotherapy and combination therapy did not (<i>p</i> = 0.1009 and <i>p</i> = 0.9999, respectively). A cumulative analysis of both hemispheres revealed that monotherapy with aspirin or cilostazol markedly reduced injury markers (<i>p</i> = 0.0002 and <i>p</i> = 0.0001, respectively), whereas combined therapy revealed no significant benefit (<i>p</i> = 0.1984). A neurological assessment indicated that the most severe deficits were in the combination therapy group. Conclusions: To the best of our knowledge, this is the first study to compare acute histopathological changes in the affected and unaffected hippocampus after a stroke in a rat model. Dual antiplatelet therapy resulted in worse outcomes (histopathological and neurological) than monotherapy.
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spelling doaj-art-df0ca1e01bcc4341a568e9c59b2d33112025-08-20T03:14:39ZengMDPI AGNeurology International2035-83772025-04-011756910.3390/neurolint17050069Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research StudyChristiana Anastasiadou0Anastasios Papapetrou1George Galyfos2Kostas Vekrellis3Patroklos Katafygiotis4Andreas Lazaris5George Geroulakos6Angelos Megalopoulos7Christos Liapis8Nikolaos Kostomitsopoulos9John Kakisis10Department of Vascular Surgery, “George Papanikolaou” General Hospital of Thessaloniki, 570 10 Exochi, GreeceDepartment of Vascular Surgery, “KAT” General Hospital of Athens, 145 61 Kifisia, GreeceVascular Unit, First Department of Propedeutic Surgery, National and Kapodistrian University of Athens, 157 72 Athens, GreeceClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, 115 27 Athens, GreeceIndependent Researcher, 157 72 Athens, GreeceDepartment of Vascular Surgery, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 157 72 Athens, GreeceDepartment of Vascular Surgery, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 157 72 Athens, GreeceDepartment of Vascular Surgery, “George Papanikolaou” General Hospital of Thessaloniki, 570 10 Exochi, GreeceDepartment of Vascular Surgery, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 157 72 Athens, GreeceClinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, 115 27 Athens, GreeceDepartment of Vascular Surgery, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 157 72 Athens, GreeceObjective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke. Materials and Methods: Twelve-week-old rats were randomly assigned to four groups, each containing six rats: a cilostazol group, an aspirin group, an aspirin plus cilostazol group, and a control group. Each substance was administered for four weeks. Permanent brain ischemia was induced over 2 h using intraluminal middle cerebral artery occlusion. A neurologic examination was conducted, followed by euthanasia and histological examination of the CA1 hippocampal region. The hematoxylin and eosin stain was used to assess the total number of intact neuronal cell bodies and pyknotic nuclei, an indicator of early irreversible neuronal injury. Results: In the ipsilateral hippocampus, monotherapy with either aspirin or cilostazol significantly reduced pyknotic nuclei compared with the control group (<i>p</i> = 0.0016 and <i>p</i> = 0.0165, respectively). However, combination therapy showed no significant difference from the controls (<i>p</i> = 0.2375). In the contralateral hippocampus, cilostazol monotherapy demonstrated significantly reduced pyknotic nuclei (<i>p</i> = 0.0098), whereas aspirin monotherapy and combination therapy did not (<i>p</i> = 0.1009 and <i>p</i> = 0.9999, respectively). A cumulative analysis of both hemispheres revealed that monotherapy with aspirin or cilostazol markedly reduced injury markers (<i>p</i> = 0.0002 and <i>p</i> = 0.0001, respectively), whereas combined therapy revealed no significant benefit (<i>p</i> = 0.1984). A neurological assessment indicated that the most severe deficits were in the combination therapy group. Conclusions: To the best of our knowledge, this is the first study to compare acute histopathological changes in the affected and unaffected hippocampus after a stroke in a rat model. Dual antiplatelet therapy resulted in worse outcomes (histopathological and neurological) than monotherapy.https://www.mdpi.com/2035-8377/17/5/69cilostazolaspirinstrokeMCAO modelhippocampusdiaschisis
spellingShingle Christiana Anastasiadou
Anastasios Papapetrou
George Galyfos
Kostas Vekrellis
Patroklos Katafygiotis
Andreas Lazaris
George Geroulakos
Angelos Megalopoulos
Christos Liapis
Nikolaos Kostomitsopoulos
John Kakisis
Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
Neurology International
cilostazol
aspirin
stroke
MCAO model
hippocampus
diaschisis
title Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
title_full Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
title_fullStr Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
title_full_unstemmed Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
title_short Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
title_sort effect of cilostazol and aspirin during hyperacute stroke phase in rats an experimental research study
topic cilostazol
aspirin
stroke
MCAO model
hippocampus
diaschisis
url https://www.mdpi.com/2035-8377/17/5/69
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