title: 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.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. zongyongzhanghust@163.com.
authors.forename: Zong-Yong
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Biomedical Research Center of Tongji University Suzhou Institute, 215101, Suzhou, Jiangsu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Yang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Biomedical Research Center of Tongji University Suzhou Institute, 215101, Suzhou, Jiangsu, China.
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Yin
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Fu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Hou
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Fu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. tsmc_nks@tsmc.edu.cn.
authors.forename: Cun-Dong
authors.initials: CD
authors.lastname: Fan
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. blsun88@163.com.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Sun
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D009026:Mortality / Q000639:trends; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality
chemical_list: D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin
keywords: Apoptosis; Blood–brain barrier; Early brain injury; Nano-curcumin; Oxidative stress; Subarachnoid hemorrhage