Dl-3-n-butylphthalide attenuates brain injury caused by cortical infarction accompanied by cranial venous drainage disturbance

Abstract

BackgroundCerebral venous disorder may have a harmful effect on ischaemic stroke; however, the underlying mechanism remains to be elucidated. Although Dl-3-n-butylphthalide is a multitarget agent for antiischaemic stroke, its neuroprotective role in brain ischaemia accompanied by brain venous disturbance remains unclear. In this study, we induced cerebral venous disturbance by the occlusion of bilateral external jugular veins (EJVs) to explore the potential mechanism of the adverse effects of cerebrovenous disorders in cerebral infarction and explore the protective effect of Dl-3-n-butylphthalide on cerebral infarction accompanied through cerebral venous disturbance.MethodsCerebral venous disturbance was induced in Sprague-Dawley rats through the permanent occlusion of bilateral EJVs, and cerebral ischaemic stroke was induced through the permanent occlusion of the right cortical branches of the middle cerebral artery. 2,3,5-triphenyltetrazolium chloride staining, MRI, Evans blue extravasation and behavioural test were performed to evaluate infarction volume, cerebral blood flow (CBF), blood–brain barrier (BBB) integrity and neurological function. Immunofluorescence staining and western blot analysis were performed to detect loss of neuron, endothelial cells, pericytes and tight junctions.ResultsBilateral EJVs occlusion did not cause cerebral infarction; however, it increased the infarction volume compared with the simple middle cerebral artery occlusion (MCAO) group, accompanied by severe neuron loss, worse neurological function, lower CBF, increased EJVs pressure, exacerbated Evans blue extravasation and brain oedema, as well as attenuated angiogenesis. Dl-3-n-butylphthalide displayed a neuroprotective effect in rats with MCAO accompanied by EJVs occlusion by reducing neuron loss, accelerating CBF restoration, promoting angiogenesis and relieving BBB damage.ConclusionBilateral EJVs occlusion did not significantly affect normal rats but aggravated brain damage in the case of ischaemic stroke. Dl-3-n-butylphthalide treatment plays a neuroprotective role in rats with MCAO accompanied by EJVs occlusion, mainly due to the promotion of CBF restoration and BBB protection.

Neuroprotective effect of Dl-3-n-butylphthalide against ischemia–reperfusion injury is mediated by ferroptosis regulation via the SLC7A11/GSH/GPX4 pathway and the attenuation of blood–brain barrier disruption

“…The results showed that the medium-dose DL-NBP alleviated MCAO-induced neurologic deficits, brain water content, and infarction area and improved nerve function and ischemic brain injury compared to the MCAO group. Previous research not only reached the same conclusion Wei et al, 2021) but also proved that BBB destruction could increase tissue swelling and lead to brain damage (Song et al, 2022). These three studies confirm the successful establishment of a model of hypoxic-ischemic brain injury but also serve as a reminder of the damage to the BBB in this injury, which has also been mentioned in other articles (Zhu et al, 2021).…”

“…Microvascular endothelial cells are the critical component of BBB, and platelet endothelial cell adhesion molecule-1 (CD31) is expressed in it. Previous research has proved that ZO-1 and occludin are essential tight junction proteins in the BBB structure, maintaining its stabilization, and their absence could destroy the BBB directly (Song et al, 2022). Co-immunostaining ZO-1 (or occludin) with CD31 could detect the integrity of the tight junction of the BBB better.…”

“…Reverse 5′-ACTCAATCACCTTCCATCGG-3′ 2D). Nissl bodies in the neurons were stained purple-blue in the cytoplasm and light blue in the nuclei (Song et al, 2022). Compared to the Sham group, the MCAO group had fewer Nissl bodies (p < 0.001, Sham vs. MCAO; Figure 2B; Supplementary Figure 1B).…”

Effects of NBP injection on the inflammatory response, oxidative stress response and vascular endothelial function in patients with ACI: A systematic review and meta-analysis

“…Studies [51,52] have shown that NBP promotes angiogenesis and improves cerebral microcirculation, which may be 1 of the mechanisms of butylphthalein treatment for ischemic stroke. Song et al [53] found in the rat model of middle cerebral artery occlusion (MCAO) that NBP plays a neuroprotective role by reducing neuron loss, accelerating cerebral blood flow (CBF) recovery, promoting angiogenesis and alleviating blood-brain barrier damage. Inflammatory reaction plays a very important role in the pathogenesis of ACI.…”

Effectiveness of butylphthalide on cerebral autoregulation in ischemic stroke patients with large artery atherosclerosis (EBCAS study): A randomized, controlled, multicenter trial

“…16 We considered that this phenomenon might be owing to the improvement of CA by butylphthalide, which keeps cerebral blood flow at a higher level and ultimately improves the prognosis of AIS patients. 17,18 In the present study, we hypothesized that butylphthalide would effectively improve CA levels in patients with AIS. Accordingly, we sought to use a randomized controlled trial to compare CA levels on day 14 after butylphthalide injection and day 90 after treatment with injection þ capsule.…”