Evaluation of cytoprotective effects of cannabidiol on neuroinflammation and neurogenesis process in rat offsprings

Abstract

Natural compounds include complex chemical compounds that exist in plants, animals and microbes. Due to their broad spectrum of pharmacological and biochemical actions, they have been widely used to treat multifactorial diseases, including cancer. In addition, their demonstrated neuroprotective properties strongly support their use in the treatment of neurological diseases. The present study investigated the effect of cannabidiol (CBD), which can easily cross the placental barrier and is known to have anti-inflammatory effects, on fetal neuroinflammation and neurogenesis in a systemic inflammation model during pregnancy. Herein, 12 weeks adult pregnant rats (n = 30) were randomly divided into 5 groups with 6 rats in each group as follows: Control, LPS (lipopolysaccharide, i.p.), LPS+CBD 5 mg/kg (i.p.), LPS+CBD10 mg/kg (i.p.) and LPS+CBD30 mg/kg (i.p.). After the injections, blood samples of rats were collected, fetuses and placentas were taken by hysterectomy. Histopathological analysis, immunohistochemical staining, ELISA and immunoblotting analysis were performed to investigate neuroinflammatory and neurogenesis parameters in fetal brain and placenta tissues. Our findings indicated that CBD administration importantly suppressed the inflammatory process in the rat fetal brain by decreasing interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and diminishing nuclear factor kappa B (NF-κB) activation. Moreover, CBD inhibited lipopolysaccharide (LPS)-induced increasing levels of neuroinflammation-associated proteins, including glial fibrillary acidic protein (GFAP), S100B and cAMP-response element binding protein (CREB). These results suggest that CBD usage in pregnancy with inflammation conditions may be an effective therapeutic option for preventing conditions that may cause neuroinflammation in the fetal brain and adversely affect neurogenesis.