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.
Abstract
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.
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