MRI Evaluation of Axonal Remodeling After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Ischemic Stroke

Abstract

Xiaoshuan enteric-coated capsule (XSEC) is a compound Chinese medicine widely used for the treatment of ischemic stroke. Enriched environment (EE) is a rehabilitative intervention designed to facilitate physical, cognitive, and social activity after brain injury. This study aimed to assess whether the XSEC and EE combination could provide synergistic efficacy in axonal remodeling compared to that with a single treatment after ischemic stroke using magnetic resonance imaging (MRI) followed by histological analysis. Rats were subjected to permanent middle cerebral artery occlusion and treated with XSEC and EE alone or in combination for 30 days. T2weighted imaging and diffusion tensor imaging (DTI) were performed to examine the infarct volume and axonal remodeling, respectively. The co-localization of Ki67 with NG2 or CNPase was examined by immunofluorescence staining to assess oligodendrogenesis. The expressions of growth associated protein-43 (GAP-43) and growth inhibitors NogoA/Nogo receptor (NgR)/RhoA/Rho-associated kinase2 (ROCK2) were measured using western blot and qRT-PCR. The Morris water maze (MWM) was performed to evaluate the cognitive function. MRI and histological measurements indicated XSEC and EE individually benefited axonal reorganization after stroke. Notably, XSEC + EE decreased infarct volume compared with XSEC or EE monotherapy and increased ipsilateral residual volume compared with vehicle group. DTI showed XSEC + EE robustly increased fractional anisotropy while decreased axial diffusivity and radial diffusivity in the injured cortex, striatum, and external capsule. Meanwhile, diffusion tensor tractography revealed XSEC + EE elevated fiber density in the cortex and external capsule and increased fiber length in the striatum and external capsule compared with the monotherapies. These MRI measurements, confirmed by histology, showed that XSEC + EE promoted axonal restoration. Additionally, XSEC + EE amplified oligodendrogenesis, decreased the expressions

Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats

“…T2-weighted imaging (T2WI) was conducted with a fast spin-echo pulse sequence with the following parameters: repetition time (TR) = 4,400 ms, echo time (TE) = 45 ms, field of view (FOV) = 3 × 3 cm 2 ,and matrix size (MS) = 256 × 256 ( Li M Z et al, 2019 ). Infarct regions were defined by the areas with hyperintensity on T2 images ( Chan et al, 2009 ).…”

“…Hematoxylin and eosin (HE) staining was performed to identify the pathological injury of brain tissues ( n = 4 per group). The number of nerve cells was measured from three non-overlapping microscopic regions randomly selected in the peri-infarct cortex, according to the previously described method ( Li M Z et al, 2019 ). Data were presented by the average number of cells per mm 2 .…”

“…The integrated optical density (IOD) in LFB staining was analyzed with the NIS-Elements Basic Research Image Collection Analysis system (Nikon, Japan). Data were expressed as the ratio of the ipsilateral IOD to the contralateral IOD ( Li M Z et al, 2019 ).…”

Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats

“…No significant difference in infraction volume was observed between EE and SE groups in our study, which is similar to recent studies in PSCI. For example, infarct volume on day 31 after MCAO in EE group is also smaller slightly, but no statistically significant difference compared with SE group 15 . This result is also observed at 14 days after MCAO 16 , possibly due to that the neuronal death is irreversible.…”

Enriched Environment Effects on Myelination of the Central Nervous System: Role of Glial Cells

“…NG2 cells have a potential function to proliferate and differentiate into OLs. The combination treatment with Xiaoshuan enteric-coated capsule (XSEC) and EE robustly increased the number of NG2+ cells in the peri-infarct cortex and striatum of MCAO rats by immunofluorescence staining [ 56 ]. And the proliferation of NG2 cells increases in response to specific reaching training of the dominant forelimb (RT) and EE in the sensorimotor cortex at day 10 [ 57 ].…”