1. Intradermal injection of icariin-HP-β-cyclodextrin improved traumatic brain injury via the trigeminal epineurium-brain dura pathway.
- Author
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Yang W, Han YH, Wang HC, Lu CT, Yu XC, and Zhao YZ
- 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
- 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.
- Published
- 2022
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