Abstract
Ethnopharmacological relevance
Buyang
Huanwu Decoction (BHD) is a common traditional Chinese medicine formula
that has been used for the treating post-stroke disability for
centuries. Nevertheless, the impact of BHD on internal capsule injury
following stroke remains unknown and warrants further investigation.
Aim of the study
This study aimed to assess the efficacy of BHD on post-stroke internal capsule integrity by using an in vivo
magnetic resonance imaging (MRI) technique and further explore the
potential mechanisms by which BHD facilitates internal capsule
reorganization after ischemic stroke.
Materials and methods
Male
Sprague-Dawley rats were subjected to permanent occlusion of the middle
cerebral artery (MCAO) to induce focal cerebral ischemia. BHD was
intragastrically administered at doses of 16.6 g/kg and 8.3 g/kg to rats
once daily for 30 consecutive days. Subsequently, an automated Digi
gait system was utilized to assess the motor function. MRI examinations,
including T2 relaxometry mapping and diffusion tensor imaging (DTI),
were conducted to detect structural alterations in the internal capsule.
Moreover, diffusion tractography was performed to evaluate internal
capsule remodeling. Pearson correlation analysis was conducted between
the gait and MRI parameters. Additionally, luxol fast blue (LFB)
staining was performed for pathological assessment of the internal
capsule. Double immunofluorescence staining was carried out to evaluate
remyelination and Notch signaling activation in the injured internal
capsule.
Results
The
gait analysis revealed that BHD treatment significantly decreased
stance time while elevating swing time, stride length, and paw area of
the MCAO rats. T2 mapping indicated obvious infarction and an elevated
T2 value, and DTI detected reduced fractional anisotropy but increased
radial diffusivity in the internal capsule following MCAO. LFB staining
further confirmed demyelination in the injured internal capsule.
However, BHD interventions effectively reversed these MRI abnormalities
and demyelination, and improved fiber density and length of the internal
capsule. Notably, the gait performances were strongly correlated to the
T2 value, fiber density, and fiber length of the internal capsule.
Particularly, BHD treatments facilitated oligodendrogenesis in the
internal capsule by elevating the numbers of Ki67/NG2, Ki67/Oligo2, and
Ki67/CNPase positive cells. Furthermore, BHD effectively inhibited the
activation of Notch signaling in the oligodendrocyte precursor cells
(OPCs), as evidenced by reduced numbers of NG2/Notch1, NG2/NICD, and
NG2/Hes5 positive cells.
Conclusion
The
present study demonstrated that BHD could promote post-stroke motor
recovery by alleviating structural damage to the internal capsule and
facilitating internal capsule reorganization. Notably, BHD treatment
enhanced oligodendrogenesis and subsequent remyelination by inhibiting
Notch signaling activation in the OPCs.
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