Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model

Ischemic stroke, triggered by the abrupt interruption of cerebrovascular blood flow, could lead to permanent neuronal cell death. Recently, multipotent neural stem cell (NSC) grafting has emerged as potential therapy to regenerate the damaged brain tissue. However, the hostile microenvironment in...

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Main Author: Nik Salleh @ Nik Abdullah, Nik Nur Hakimah
Format: Thesis
Language:English
Published: 2023
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Online Access:http://eprints.usm.my/58813/1/08-NIK%20NUR%20HAKIMAH%20BINTI%20NIK%20SALLEH%20%40%20NIK%20ABDULLAH%20%20-%20FINAL%20THESIS%20P-SKM002419%28R%29%20-24%20pages.pdf
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spelling my.usm.eprints.58813 http://eprints.usm.my/58813/ Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model Nik Salleh @ Nik Abdullah, Nik Nur Hakimah RC31-1245 Internal medicine Ischemic stroke, triggered by the abrupt interruption of cerebrovascular blood flow, could lead to permanent neuronal cell death. Recently, multipotent neural stem cell (NSC) grafting has emerged as potential therapy to regenerate the damaged brain tissue. However, the hostile microenvironment in the ischemic brain region is challenging for the survival of transplanted cells. In this regards, NSC culture was optimized with baicalein-enriched fraction (BEF) from Oroxylum indicum- to enhance the NSC survival rate after transplantation into ischemic brain. Baicalein is one of the major flavonoids present in O. indicum and has been reported to have neuroprotective effects. In this study, BEF was successfully fractionated from the leaves of O. indicum and quantified using HPLC and its radical scavenging activity was compared to synthetic baicalein as positive control. Ischemic stroke rat model was established using endothelin-1 (ET-1) which constrict the middle cerebral artery (MCA) to induce ischemic damage in the brain. In vitro expandable NSCs were preconditioned with BEF at optimum dosage of 3.125 μg/ml for 48 hours as determined through MTT assay before the cells were transplanted into the ET-1 induced ischemic stroke rat groups. Rat behaviours and stroke severity were observed and recorded for 14 days. Improvements in stroke behaviours occurred within 14 days after the transplantation of BEF-preconditioned NSC compared to non-preconditioned NSC transplantation group. Through TTC staining, the BEF-preconditioned NSC-treated group showed significant reduced brain infarct (11.535 ± 1.44%), compared to non-preconditioned NSC-treated group (17.784 ± 2.33%) and non-treated group (23.807 ± 2.60%). In addition, BEF-preconditioned NSC-treated group also significantly reduced neuronal degradation and inflammation, while also increased blood vessel density compared to the other groups. As a conclusion, this study proved the potential of BEF extracted from O. indicum in contributing to the upregulation of NSC proliferation- and significantly improved the therapeutic potential of NSCs to repair damaged neuronal tissue- ischemic stroke rats. 2023-02 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/58813/1/08-NIK%20NUR%20HAKIMAH%20BINTI%20NIK%20SALLEH%20%40%20NIK%20ABDULLAH%20%20-%20FINAL%20THESIS%20P-SKM002419%28R%29%20-24%20pages.pdf Nik Salleh @ Nik Abdullah, Nik Nur Hakimah (2023) Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model. Masters thesis, Universiti Sains Malaysia.
institution Universiti Sains Malaysia
building Hamzah Sendut Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Sains Malaysia
content_source USM Institutional Repository
url_provider http://eprints.usm.my/
language English
topic RC31-1245 Internal medicine
spellingShingle RC31-1245 Internal medicine
Nik Salleh @ Nik Abdullah, Nik Nur Hakimah
Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model
description Ischemic stroke, triggered by the abrupt interruption of cerebrovascular blood flow, could lead to permanent neuronal cell death. Recently, multipotent neural stem cell (NSC) grafting has emerged as potential therapy to regenerate the damaged brain tissue. However, the hostile microenvironment in the ischemic brain region is challenging for the survival of transplanted cells. In this regards, NSC culture was optimized with baicalein-enriched fraction (BEF) from Oroxylum indicum- to enhance the NSC survival rate after transplantation into ischemic brain. Baicalein is one of the major flavonoids present in O. indicum and has been reported to have neuroprotective effects. In this study, BEF was successfully fractionated from the leaves of O. indicum and quantified using HPLC and its radical scavenging activity was compared to synthetic baicalein as positive control. Ischemic stroke rat model was established using endothelin-1 (ET-1) which constrict the middle cerebral artery (MCA) to induce ischemic damage in the brain. In vitro expandable NSCs were preconditioned with BEF at optimum dosage of 3.125 μg/ml for 48 hours as determined through MTT assay before the cells were transplanted into the ET-1 induced ischemic stroke rat groups. Rat behaviours and stroke severity were observed and recorded for 14 days. Improvements in stroke behaviours occurred within 14 days after the transplantation of BEF-preconditioned NSC compared to non-preconditioned NSC transplantation group. Through TTC staining, the BEF-preconditioned NSC-treated group showed significant reduced brain infarct (11.535 ± 1.44%), compared to non-preconditioned NSC-treated group (17.784 ± 2.33%) and non-treated group (23.807 ± 2.60%). In addition, BEF-preconditioned NSC-treated group also significantly reduced neuronal degradation and inflammation, while also increased blood vessel density compared to the other groups. As a conclusion, this study proved the potential of BEF extracted from O. indicum in contributing to the upregulation of NSC proliferation- and significantly improved the therapeutic potential of NSCs to repair damaged neuronal tissue- ischemic stroke rats.
format Thesis
author Nik Salleh @ Nik Abdullah, Nik Nur Hakimah
author_facet Nik Salleh @ Nik Abdullah, Nik Nur Hakimah
author_sort Nik Salleh @ Nik Abdullah, Nik Nur Hakimah
title Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model
title_short Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model
title_full Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model
title_fullStr Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model
title_full_unstemmed Therapeutic Potential of Neural Stem Cells Preconditioned with Baicalein-Enriched Fraction in Ischemic Stroke Rat Model
title_sort therapeutic potential of neural stem cells preconditioned with baicalein-enriched fraction in ischemic stroke rat model
publishDate 2023
url http://eprints.usm.my/58813/1/08-NIK%20NUR%20HAKIMAH%20BINTI%20NIK%20SALLEH%20%40%20NIK%20ABDULLAH%20%20-%20FINAL%20THESIS%20P-SKM002419%28R%29%20-24%20pages.pdf
http://eprints.usm.my/58813/
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