The blood-brain barrier (BBB) is a protective structure that helps maintaining the homeostasis in cerebral microenvironment by limiting the passage of molecules into the brain. BBB is formed by closely conjugated endothelial cells, with astrocytic endfeet surrounded and extracellular matrix (ECM) consolidated. Numerous neurological diseases can cause disturbance of BBB, leading to brain edema and neurological dysfunctions. The low-density lipoprotein (LDL) receptor–related protein 1 (LRP-1), a member of the LDL receptor gene family, is involved in a lot of important processes in the brain under both physiological and pathological conditions. As a membrane receptor, LRP-1 interacts with a variety of ligands and mediates the internalization of several important substances. LRP-1 is found responsible for inducing the opening of BBB following ischemic attack. It has also been reported that LRP-1 regulates several tight junction proteins and mediates the clearance of major ECM-degrading proteinases. In this review, we briefly discussed the role of LRP-1 in regulating BBB integrity by modulating tight junction proteins, endothelial cells and the remodeling of ECM.

Lipid droplets (LDs), serving as the convergence point of energy metabolism and multiple signaling pathways, have garnered increasing attention in recent years. Different cell types within the central nervous system (CNS) can regulate energy metabolism to generate or degrade LDs in response to diverse pathological stimuli. This article provides a comprehensive review on the composition of LDs in CNS, their generation and degradation processes, their interaction mechanisms with mitochondria, the distribution among different cell types, and the roles played by these cells—particularly microglia and astrocytes—in various prevalent neurological disorders. Additionally, we also emphasize the paradoxical role of LDs in post-cerebral ischemia inflammation and explore potential underlying mechanisms, aiming to identify novel therapeutic targets for this disease.

Caveolin-1 is the principal marker of caveolae in endothelial cells. It plays an important role in physiological and pathological conditions of the blood-brain barrier and serves as a mediator in drug delivery through the blood-brain barrier. Caveolin-1 is related to the diminished expression of tight junction-associated proteins and metabolic pinocytosis vesicles when the blood-brain barrier is destroyed by outside invaders or malignant stimulus. The permeability of the blood-brain barrier, regulated by types of drugs or physical irradiation, is connected with drug transportation with the participation of caveolin-1. Caveolin-1, which serves as a platform or medium for signal transduction, cooperates with several signal molecules by forming a complex. Silencing of caveolin-1 and disruption of caveolae can attenuate or remove pathological damage and even engender the opposite effects in the blood-brain barrier. This review considers the role of caveolin-1 in the blood-brain barrier that may have profound implications for central nervous system disease and drug delivery through the blood-brain barrier.

High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine-like activity, is involved in several neurological diseases by mediating inflammatory response. In this study, a lateral head rotation device was used to establish a rat diffuse axonal injury (DAI) model. The dynamic expression of HMGB1, apoptosis-associated proteins, and proinflammatory cytokines were detected by Western blot, and neuronal apoptosis was observed by TUNEL staining. The extracellular release of HMGB1 and the accumulation ofβ-APP were observed by immunofluorescence and immunohistochemistry, respectively. The brain injury was indicated by modified neurological severity score (mNSS), brain water content (BWC), and the extravasation of Evans blue. We showed that HMGB1 level obviously decreased within 48 h after DAI, accompanied by neuronal apoptosis, the activation of caspases 3 and 9, and the phosphorylation of BCL-2. Inhibiting HMGB1 with glycyrrhizic acid (GL) can suppress the activation of apoptosis-associated proteins and inhibit the expression of proinflammatory cytokines, which ameliorated motor and cognitive deficits, reduced neuronal apoptosis, and protected the integrity of blood brain barrier (BBB) and axonal injury after experimental DAI in rats. Thus, HMGB1 may be involved in the inflammatory response after DAI, and inhibition of HMGB1 release with GL can notably alleviate the brain injury after DAI.

Early brain injury (EBI) plays a key role in determining the prognosis of patients suffering from subarachnoid hemorrhage (SAH). Resveratrol, a natural polyphenol, serves a neuroprotection function on EBI after SAH. However, the potential mechanism of resveratrol on EBI remains to be elucidated. Akt, also known as protein kinase B, and mammalian target of rapamycin (mTOR), the downstream protein of Akt, play key roles in cell survival and apoptosis, cell cycle regulation, and cellular protein homeostasis. In the present study, we examined the effect of resveratrol on EBI and their potential relationship with the Akt/mTOR pathway, autophagy, and apoptosis. Rats received intraperitoneal administration of resveratrol or vehicle immediately after establishing SAH model. We found that mortality and brain edema were significantly lower, whereas the neurological score was higher for resveratrol-treated rats. HE staining showed that resveratrol significantly reduced the neuronal pyknosis and swelling in the resveratrol-treated rats compared with SAH rats. The results were assessed by western blot, reverse transcription-PCR , and immunohistochemistry and immunofluorescence at 24 h after injury to determine changes in the expression of the Akt/mTOR signaling pathway, autophagy, and apoptosis proteins. Western blot analysis showed that the expression of beclin-1, LC3-II, LC3-II/LC3-I, and Bcl-2 was increased in resveratrol-treated rats, whereas the expression of p-Akt, p-mTOR, p62, cleaved caspase-3, caspase-9, and Bcl-2-associated X protein was decreased. Immunohistochemistry analysis of beclin-1, LC3-B treated with resveratrol alone or in combination with 3-methyladenine (autophagy inhibitor) suggested that resveratrol induced the autophagy process and the inhibitor blocked the occurrence of autophagy, and also increased the number of terminal deoxynucleotidyl transferase-mediated digoxigenin-DUTP-biotin nick-end labeling (+) cells. Taken together, these findings indicate that resveratrol exerts neuroprotective effects on EBI after SAH by regulating autophagy and apoptosis mediated by the Akt/mTOR pathway.