Effect of a water-soluble form of dihydroquercetin on age-dependent LPS-induced gliovascular remodeling of the substantia nigra in rats

Abstract

Background. The molecular and cellular mechanisms of action of the water-soluble form of dihydroquercetin (DHA-VF) on neurogliovascular units, age-related disturbances of intrasystem connections that may underlie neuroinflammatory and neurodegenerative diseases, remain unclear.The aim: to study structural changes of microcirculatory vessels and functional responses of micro- and astroglial cells in the substantia nigra of young and old rats in response to intranigral injection of lipopolysaccharide (LPS) and subsequent oral administration of DHA-VF.Methods. Young (250-320 g) and old (390-450 g) Wistar rats were injected with 2 μL LPS solution at a concentration of 0.01 μL/mL (experimental group; n=24) or 2 μL sterile physiological solution (control group; n=12) into the substantia nigra area of the brain using a stereotaxic device. Half of the animals in the experimental groups (6 animals of each age group) were given 2 ml of a solution containing DHA-VF at a concentration of 3 mg/mL daily by gavage with a probe. After 8 weeks, the animals were decapitated and cryostat sections were obtained for histochemical (FITC-labeled tomato lectin) and immunohistochemical (antibodies against GFAP and CD-11β) staining of vascular endothelium and glial cells, respectively. Results. 8 weeks after LPS administration to old rats in the CS, a significant excess of areas occupied by cell bodies and processes of microglial and astroglial cells as well as the number of vessels at standard sites was found compared to both young animals exposed to similar exposure and old control animals. Oral administration of DHA-VF to rats significantly reduced LPS-induced glial activation in young and old animals. In addition, administration of DHA-VF to old animals reduced the intensity of LPS-induced microvascular remodeling of the CS. Conclusions. LPS administration in the rat CS induces neuroinflammation and vascular angiogenesis, which are maximally expressed in old animals. Administration of DHA-VF for 8 weeks significantly reduced these LPS-induced changes.