Filgrastim Protects the Cerebellar Cortex Against TNF-α/Bax Enhanced Apoptosis After Aluminum Toxicity in Albino Rats. Histological and Immunohistochemical Study

Abstract

Introduction: Aluminum (Al) is a strong toxicant affecting the brain neurons. Filgrastim can be a promising protective drug.Aim of the Work: Evaluation of the neuro-alleviating role of Filgrastim on the Aluminum-induced neuronal toxicity in the cerebellar cortex.Material and Methods: Thirty-two adult male albino rats were used in this study. The rats were divided into sets; group I (control group): rats received no drugs. Group II (Aluminum Chloride group): rats received AlCl3 at a dose of (150 mg/kg/bw; orally) dissolved in normal saline for 21 days, group III (Filgrastim +AlCl3 group): rats were trated with aluminum chloride (AlCl3) as in group II for 21 days, and were injected subcutaneously with Filgrastim at a dose of (40 μg/kg/day) for three days before AlCl3 and continued for another 21 days with AlCl3 (Filgrastim was injected 30 minutes before AlCl3). Following fixation, skulls were opened and the cerebellar cortex samples were directly handled for light and electron microscopic examination.Results: The results of this study lead to the conclusion that Filgrastim protects the cerebellar cortex against aluminum toxicity. The histological observations showed that group II revealed extensive cerebellar cortex affection with vacuolated apoptotic cells and degenerated nerve fibers. Calbindin immunoreactivity showed a significant down-regulation (P<0.05) in Purkinje cells, while Bax and TNF-α immunoreactivity were significantly up-regulated (P < 0.05) in all layers of the cerebellar cortex. Filgrastim pre-treatment in group III improved all these histological, immunohistochemical, and ultrastructural parameters.Conclusion: The results showed that Filgrastim can protect the cerebellar cortex from the toxic effect of Aluminium through anti-inflammatory and anti-apoptotic mechanisms.