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Intradermal injection of icariin-HP-β-cyclodextrin improved traumatic brain injury via the trigeminal epineurium-brain dura pathway.
- Source :
-
Journal of drug targeting [J Drug Target] 2022 Jun; Vol. 30 (5), pp. 557-566. Date of Electronic Publication: 2022 Jan 24. - Publication Year :
- 2022
-
Abstract
- The lower bioavailability after oral administration limited icariin applications in central nervous system. Icariin/HP-β-cyclodextrin (HP-β-CD) inclusion complex was prepared for acute severe opening traumatic brain injury (TBI) via facial intradermal (i.d.) in the mystacial pad. After fluid percussion-induced TBI, icariin/HP-β-CD at 0.4 mg/kg i.d. preserved more neurons and oligodendrocytes than intranasal injection (i.n.) or intravenous injection via tail vein (i.v.) and decreased microglia and astrocyte activation. Icariin/HP-β-CD i.d. reduced apoptosis in cortical penumbra while i.n. and i.v. showed weak or no effects. Icariin/HP-β-CD i.d. reduced Evans blue leakage and altered CD34, ZO-1, Claudin-5, and beta-catenin expression after TBI. Moreover, icariin/HP-β-CD promoted human umbilical vein endothelial cells proliferation. Thus, Icariin/HP-β-CD i.d. improved TBI, including blood-brain barrier opening. Fluorescein 5-isothiocyanate (FITC) and 3,3'-Dioctadecyloxacarbocyanine perchlorate (DiOC18(3)) mimic HP-β-CD and icariin respectively. FITC and DiOC18(3) were similarly delivered to trigeminal epineurium, perineurium and perivascular spaces or tissues, caudal dura mater, and scattered in trigeminal fasciculus, indicating that icariin/HP-β-CD was delivered to the brain via trigeminal nerve-dura mater-brain pathways. In sum, intradermal injection in mystacial pad might deliver icariin/HP-β-CD to the brain and icariin/HP-β-CD improved acute severe opening TBI.
- Subjects :
- 2-Hydroxypropyl-beta-cyclodextrin metabolism
Brain metabolism
Dura Mater
Endothelial Cells
Flavonoids
Fluorescein-5-isothiocyanate
Humans
Injections, Intradermal
Peripheral Nerves
Solubility
Brain Injuries, Traumatic drug therapy
Brain Injuries, Traumatic metabolism
beta-Cyclodextrins metabolism
beta-Cyclodextrins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2330
- Volume :
- 30
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of drug targeting
- Publication Type :
- Academic Journal
- Accession number :
- 35023434
- Full Text :
- https://doi.org/10.1080/1061186X.2021.2023159