Dl‐3n‐butylphthalide improves traumatic brain injury recovery via inhibiting autophagy‐induced blood‐brain barrier disruption and cell apoptosis

Abstract

Blood-brain barrier (BBB) disruption and neuronal apoptosis are important pathophysiological processes after traumatic brain injury (TBI). In clinical stroke, Dl-3nbutylphthalide (Dl-NBP) has a neuroprotective effect with anti-inflammatory, anti-oxidative, anti-apoptotic and mitochondrion-protective functions. However, the effect and molecular mechanism of Dl-NBP for TBI need to be further investigated.Here, we had used an animal model of TBI and SH-SY5Y/human brain microvascular endothelial cells to explore it. We found that Dl-NBP administration exerts a neuroprotective effect in TBI/OGD and BBB disorder, which up-regulates the expression of tight junction proteins and promotes neuronal survival via inhibiting mitochondrial apoptosis. The expressions of autophagy-related proteins, including ATG7, Beclin1 and LC3II, were significantly increased after TBI/OGD, and which were reversed by Dl-NBP treatment both in vivo and in vitro. Moreover, rapamycin treatment had abolished the effect of Dl-NBP for TBI recovery. Collectively, our current studies indicate that Dl-NBP treatment improved locomotor functional recovery after TBI by inhibiting the activation of autophagy and consequently blocking the junction protein loss and neuronal apoptosis. Dl-NBP, as an anti-inflammatory and anti-oxidative drug, may act as an effective strategy for TBI recovery.Fangfang Wu and Ke Xu contributed equally to this work. | 1221WU et al.

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

“…Growing evidence has indicated that overactivated autophagy under pathological conditions can trigger cell death and BBB damage; for example, following a stroke in diabetic mice, the expression of autophagy-related proteins was increased, while that of the TJ protein occludin was decreased, and 3-MA reversed these effects ( 70 , 71 ). Wu et al reported that Dl-3n-butylphthalide can exert neuroprotective effects by inhibiting autophagy and blocking TJ protein loss ( 72 ). Our previous study also revealed that hyperglycemia increased LC3 II/I expression following cerebral I/R injury ( 34 ).…”

Healthy Serum-Derived Exosomes Improve Neurological Outcomes and Protect Blood–Brain Barrier by Inhibiting Endothelial Cell Apoptosis and Reversing Autophagy-Mediated Tight Junction Protein Reduction in Rat Stroke Model

“…Pericyte apoptosis also increases BBB permeability, which, in turn, diminishes the stability of the brain microenvironment ( Armulik et al, 2010 ; Liu S. et al, 2012 ). The biochemical compounds targeting endothelial cell and pericyte apoptosis exert promising effects on functional recovery after central nervous system injury ( Hu et al, 2017 ; Song et al, 2018 ; Wu et al, 2020 ).…”

Optical coherence tomography microscopy in experimental traumatic brain injury

“…Two days after the initial TBI, in the aged animal group, we were able to detect a decrease in the apparent lesion area which could show a delayed response in older animals compared with young ones, as already reported by other groups (Brickler, Morton, Hazy, & Theus, 2018; Kumar et al, 2013; Marker et al, 2010). Due to the fact that our OCT setups cannot discriminate individual cells within the newly form scar, our findings suggest that, at least for the acute phase of the TBI, this technique evaluates water content and not reflected patterns due to cell density, as in this period water metabolism varies faster that cellular migration or proliferation (Wu et al, 2020). When measuring the apparent OCT lesion, no difference was found between young and old animal 48 hr after the initial TBI.…”