Effects of <i>Xiaoshuan</i> Enteric-Coated Capsule on White and Gray Matter Injury Evaluated by Diffusion Tensor Imaging in Ischemic Stroke

Zhang, Jian; Chen, Shengpan; Shi, Weili; Li, Man-Zhong; Zhan, Yuan; Yang, Le; Zou, Haiyan; Lei, Jianfeng; Chai, Xiangping; Gao, Kuo; Liu, Junjie; Wang, Wei; Wang, Yong; Zhao, Hui

doi:10.1177/0963689718802755

Cited by 8 publications

(4 citation statements)

References 49 publications

(65 reference statements)

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“…Arterial spin labeling (ASL) could detect CBF (Zhang et al, 2016 , 2019 ). The relative CBF value (rCBF) of the periinfarct cortex or striatum was the ipsilateral CBF value divided by the contralateral CBF value (Yang et al, 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes

Lin

et al. 2023

Front. Cell. Neurosci.

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2,3,5,6-Tetramethylpyrazine (TMP) as an active ingredient extracted from a traditional Chinese herbal medicine Ligusticum chuanxiong Hort. has been proved to penetrate blood-brain barrier (BBB) and show neuroprotective effects on cerebral ischemia. However, whether TMP could regulate astrocytic reactivity to facilitate neurovascular restoration in the subacute ischemic stroke needs to be urgently verified. In this research, permanent occlusion of the middle cerebral artery (MCAO) model was conducted and TMP (10, 20, 40 mg/kg) was intraperitoneally administrated to rats once daily for 2 weeks. Neurological function was evaluated by motor deficit score (MDS). Magnetic resonance imaging (MRI) was implemented to analyze tissue injury and cerebral blood flow (CBF). Magnetic resonance angiography (MRA) was applied to exhibit vascular signals. Transmission electron microscopy (TEM) was performed to detect the neurovascular unit (NVU) ultrastructure. Haematoxylin and eosin (HE) staining was utilized to evaluate cerebral histopathological lesions. The neurogenesis, angiogenesis, A1/A2 reactivity, aquaporin 4 (AQP4) and connexin 43 (Cx43) of astrocytes were observed with immunofluorescent staining. Then FGF2/PI3K/AKT signals were measured by western blot. Findings revealed TMP ameliorated neurological functional recovery, preserved NVU integrity, and enhanced endogenous neurogenesis and angiogenesis of rats with subacute ischemia. Shifting A1 to A2 reactivity, suppressing excessive AQP4 and Cx43 expression of astrocytes, and activating FGF2/PI3K/AKT pathway might be potential mechanisms of promoting neurovascular restoration with TMP after ischemic stroke.

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Section: Methodsmentioning

confidence: 99%

Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes

Lin

et al. 2023

Front. Cell. Neurosci.

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“…ASL raw data and CBF maps were obtained by Paravision version 5.1 software. The CBF values (mL/100 g/min) of the bilateral peri-infarct cortex, external capsule, and internal capsule were acquired based on our previous method ( Zhang et al, 2016 ; Zhang et al, 2019 ). The relative CBF (rCBF) was the ratio of the ipsilateral CBF to the contralateral CBF.…”

Section: Methodsmentioning

confidence: 99%

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

Feng

Lei

et al. 2022

Front. Pharmacol.

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Ischemic stroke elicits white matter injury typically signed by axonal disintegration and demyelination; thus, the development of white matter reorganization is needed. 2,3,5,6-Tetramethylpyrazine (TMP) is widely used to treat ischemic stroke. This study was aimed to investigate whether TMP could protect the white matter and promote axonal repair after cerebral ischemia. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with TMP (10, 20, 40 mg/kg) intraperitoneally for 14 days. The motor function related to gait was evaluated by the gait analysis system. Multiparametric magnetic resonance imaging (MRI) was conducted to noninvasively identify gray-white matter structural integrity, axonal reorganization, and cerebral blood flow (CBF), followed by histological analysis. The expressions of axonal growth-associated protein 43 (GAP-43), synaptophysin (SYN), axonal growth-inhibitory signals, and guidance factors were measured by Western blot. Our results showed TMP reduced infarct volume, relieved gray-white matter damage, promoted axonal remodeling, and restored CBF along the peri-infarct cortex, external capsule, and internal capsule. These MRI findings were confirmed by histopathological data. Moreover, motor function, especially gait impairment, was improved by TMP treatment. Notably, TMP upregulated GAP-43 and SYN and enhanced axonal guidance cues such as Netrin-1/DCC and Slit-2/Robo-1 but downregulated intrinsic growth-inhibitory signals NogoA/NgR/RhoA/ROCK-2. Taken together, our data indicated that TMP facilitated poststroke axonal remodeling and motor functional recovery. Moreover, our findings suggested that TMP restored local CBF, augmented guidance cues, and restrained intrinsic growth-inhibitory signals, all of which might improve the intracerebral microenvironment of ischemic areas and then benefit white matter remodeling.

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“…The recovery of axonal integrity at 72 h and 1 week after stroke onset on ambroxol animals is consistent with previous reports of FA return to baseline after 3 weeks if no permanent damage occurs to the axons. 36 , 84 …”

Section: Discussionmentioning

confidence: 99%

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

Patzwaldt

Berezhnoy

Ionescu

et al. 2023

Brain Communications

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Ambroxol is a well-known mucolytic expectorant, which has gained much attention in Amyotrophic lateral sclerosis, Parkinson’s and Gaucher’s disease. A specific focus has been placed on Ambroxol’s glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson’s disease. However, Ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that Ambroxol could have a direct impact on neuronal rescue if administered directly after ischemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, edema, white matter integrity, resting state functional magnetic resonance imaging and behavior for one month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex-vivo nuclear magnetic resonance spectroscopy. Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic edema, reduced white matter degeneration, reduced necrosis, improved behavioral outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post stroke proposes several metabolites that are capable of minimizing post-ischemic damage and that presented prominent shifts during Ambroxol treatment in comparison to controls. Taking everything together, we propose that Ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of Ambroxol administration following stroke onset reduced ischemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.

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Effects of Xiaoshuan Enteric-Coated Capsule on White and Gray Matter Injury Evaluated by Diffusion Tensor Imaging in Ischemic Stroke

Cited by 8 publications

References 49 publications

Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes

Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes

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

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

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