Dl-3-n-butylphthalide promotes remyelination process in cerebral white matter in rats subjected to ischemic stroke

Cheng, Xi; Wang, Huibin; Liu, Chang; Zhong, Shanshan; Niu, Xueli; Zhang, Xiuchun; Qi, Ruiqun; Zhao, Shanshan; Zhang, Xiaoqian; Qu, Huiling; Zhao, Chuansheng

doi:10.1016/j.brainres.2019.03.017

Cited by 19 publications

(22 citation statements)

References 29 publications

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“…NBP has been shown to promote remyelination and increase the integrity of white matter after endothelin-1-induced focal permanent ischemic stroke in rats (Cheng et al, 2019). Here, we examined the effect of dl-NBP on white matter integrity in a focal transient ischemic stroke model.…”

Section: Dl-nbp Treatment Promoted the Integrity Of White Matter Aftementioning

confidence: 97%

“…In 1980, the racemic compound dl-3-n-butylphthalide (dl-NBP) was synthesized, and it resolved the problem of limited resources from plant extracts . Dl-NBP was approved by the FDA of China for the treatment of ischemic stroke in 2002 , and it has been approved by the FDA of the USA to undergo a phase II trial for the treatment of ischemic stroke (Cheng et al, 2019). It is currently used in the acute phase of ischemic stroke in clinic and is a promising therapeutic agent for ischemic stroke .…”

Section: Introductionmentioning

confidence: 99%

“…Increasing the white matter integrity (Etherton et al, 2017) and increasing the integrity of BBB (Jiang et al, 2017) contribute to the neurological functional recovery. Using an endothelin-1-induced focal permanent stroke model, Cheng et al reported that dl-NBP enhanced the remyelination process and increased white matter integrity by promoting differentiation and maturation of oligodendrocyte precursor cells in peri-lesional white matter (Cheng et al, 2019). However, it is not clear whether dl-NBP could promote white matter integrity after transient focal ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

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Dl-NBP (Dl-3-N-Butylphthalide) Treatment Promotes Neurological Functional Recovery Accompanied by the Upregulation of White Matter Integrity and HIF-1α/VEGF/Notch/Dll4 Expression

et al. 2020

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Dl-3-n-butylphthalide (dl-NBP) was approved by the FDA of China for the treatment of acute ischemic stroke. Dl-NBP has been shown to promote neurological functional recovery and enhance white matter integrity using an endothelin-1-induced focal permanent cerebral ischemia model, which could mimic those patients who have no opportunity to receive either tissue plasminogen activator (tPA) thrombolysis or endovascular therapy. However, it is not clear whether dl-NBP could promote neurological functional recovery in a focal transient cerebral ischemia model, which could mimic those patients who have the opportunity to receive either tPA thrombolysis or endovascular therapy. In this study, using a model of middle cerebral artery occlusion in mice, we aim to explore the effect of two-week dl-NBP treatment on neurological functional recovery after ischemic stroke as well as its underlying mechanism. Our results showed that dl-NBP treatment promoted functional recovery assessed by neurological scores and an adhesive remove test, and this improved the integrity of white matter after 60-min ischemia and 14-day reperfusion. In addition, dl-NBP increased the number of RECA-1 positive vessels and enhanced the expression of the tight junction protein occludin. More importantly, dl-NBP also promoted the expression of hypoxiainduced factor-1a, the vascular endothelial growth factor, Notch, and delta-like ligand 4. In conclusion, our study provides evidence that dl-NBP treatment could also promote functional recovery after focal transient ischemia stroke, and this recovery is associated with upregulated white matter integrity, microvessels, and the tight junction protein occludin. Our results suggested that, in future, dl-NBP may also be applied in clinic to promote functional recovery during the later phase of focal transient ischemic stroke.

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Section: Dl-nbp Treatment Promoted the Integrity Of White Matter Aftementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dl-NBP (Dl-3-N-Butylphthalide) Treatment Promotes Neurological Functional Recovery Accompanied by the Upregulation of White Matter Integrity and HIF-1α/VEGF/Notch/Dll4 Expression

et al. 2020

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“…It has been approved by National Medical Products Administration for the treatment of ischemic stroke in China since 2002. Previous studies have shown that NBP could have therapeutic effects on ischemic stroke through multiple mechanisms, including reducing the inflammatory response of ischemic stroke [1], attenuating microglia activation [2], decreasing the levels of cytokines such as tumor necrosis factor-alpha (TNFα), reducing blood-brain barrier (BBB) damage and brain edema [3], and promotes remyelination process [6]. Although the original cause of the brain damage induced by ICH is different from ischemic stroke, the subsequent inflammatory pathological pathways and consequent brain edema in ICH share many common characteristics with ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

L-3-n-butylphthalide attenuates inflammation and brain edema in rat intracerebral hemorrhage model

Zeng

Gong

2019

Preprint

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Background：Previous studies have shown that L-3-n-butylphthalide(NBP), which is a compound found in Apium graveolens Linn seed extracts, could have therapeutic effects on acute ischemic stroke through anti-inflammation and by reducing brain edema. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some characteristics with ischemic stroke. Methods：We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging (MRI) was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. Results： The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Conclusions：Our results suggested that NBP attenuates inflammation and brain edema in rat ICH model. Therefore, our findings also show the potential for clinical application of NBP in the treatment of ICH. Keywords: L-3-n-butylphthalide; intracerebral haemorrhage; blood-brain barrier; brain edema; anti-inflammation

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“…It has been approved by National Medical Products Administration for the treatment of ischemic stroke in China since 2002. Previous studies have shown that NBP could have a neuroprotective effect on ischemic stroke through multiple mechanisms, including reducing the inflammatory response of ischemic stroke [1], attenuating microglia activation [2], decreasing the levels of cytokines such as tumor necrosis factor-alpha (TNFα), reducing blood-brain barrier (BBB) damage and brain edema [3], and promotes remyelination process [6]. Although the original cause of the brain damage induced by ICH is different from ischemic stroke, the subsequent inflammatory pathological pathways and consequent brain edema in ICH share many common characteristics with ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

Zeng

Gong

2019

Preprint

View full text Add to dashboard Cite

Background：Previous studies have shown that L-3-n-butylphthalide(NBP), which is a compound found in Apium graveolens Linn seed extracts, could have neuroprotective effects on acute ischemic stroke through anti-inflammation and by reducing brain edema. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some characteristics with ischemic stroke. Methods：We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging (MRI) was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. Results： The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Conclusions：Our results suggested that NBP have a neuroprotective effect by reducing inflammation and brain edema in rat ICH model. Therefore, our findings also show the potential for clinical application of NBP in the treatment of ICH.

show abstract

Dl-3-n-butylphthalide promotes remyelination process in cerebral white matter in rats subjected to ischemic stroke

Cited by 19 publications

References 29 publications

Dl-NBP (Dl-3-N-Butylphthalide) Treatment Promotes Neurological Functional Recovery Accompanied by the Upregulation of White Matter Integrity and HIF-1α/VEGF/Notch/Dll4 Expression

Dl-NBP (Dl-3-N-Butylphthalide) Treatment Promotes Neurological Functional Recovery Accompanied by the Upregulation of White Matter Integrity and HIF-1α/VEGF/Notch/Dll4 Expression

L-3-n-butylphthalide attenuates inflammation and brain edema in rat intracerebral hemorrhage model

L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

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