Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

Abstract

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

• Authors: Zong-Yong Zhang, Ming Jiang, Jie Fang, Ming-Feng Yang, Shuai Zhang, Yan-Xin Yin, Da-Wei Li, Lei-Lei Mao, Xiao-Yan Fu, Ya-Jun Hou, Xiao-Ting Fu, Cun-Dong Fan, Bao-Liang Sun
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 54 Issue 1 Pg. 1-14 (01 2017) ISSN: 1559-1182 [Electronic] United States
• PMID: 26708209 (Publication Type: Journal Article)

Chemical References

• Inflammation Mediators
• Neuroprotective Agents
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Curcumin

Topics

• Animals
• Blood-Brain Barrier (drug effects, metabolism)
• Curcumin (administration & dosage, metabolism)
• Dose-Response Relationship, Drug
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Lactic Acid (administration & dosage, metabolism)
• Male
• Mortality (trends)
• Nanoparticles (administration & dosage, metabolism)
• Neuroprotective Agents (administration & dosage, metabolism)
• Oxidative Stress (drug effects, physiology)
• Polyglycolic Acid (administration & dosage, metabolism)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Subarachnoid Hemorrhage (drug therapy, metabolism, mortality)