Please cite this article in press as: El-Akabawy, G., El-Kholy, W., Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2014.01.003 ARTICLE IN PRESS G Model AANAT-50849; No. of Pages 10 Annals of Anatomy xxx (2014) xxx–xxx Contents lists available at ScienceDirect Annals of Anatomy j ourna l h omepage: www.elsevier.de/aanat RESEARCH ARTICLE Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats Gehan El-Akabawy ∗ , Wael El-Kholy Menoufia University, Department of Anatomy and Embryology, Faculty of Medicine, Menoufia, Egypt a r t i c l e i n f o Article history: Received 3 August 2013 Received in revised form 17 January 2014 Accepted 31 January 2014 Available online xxx Keywords: Ginger Diabetes Brain Histology Immunohistochemistry s u m m a r y Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxida- tive stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a pro- tective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. © 2014 Elsevier GmbH. All rights reserved. 1. Introduction Diabetes mellitus (DM) is one of the most common chronic metabolic disorders leading to complications in multiple organs and systems. These complications often result in either morbidity or mortality (Perkins and Bril, 2005). Diabetic encephalopathy is one of the complications that occur due to gradually developing end-organ damage in the central nervous system (Northam and Cameron, 2013). The damage could be as a result of chronically increased intracellular glucose concentration leading to several structural, neurochemical, and neurodegenerative changes in dif- ferent regions in the brain including the frontal cortex (Kumar et al., 2008), hippocampus (Pamidi and Satheesha Nayak, 2012), and cerebellum (Hernandez-Fonseca et al., 2009). These pathological changes underpin different cognitive, motor, and neuroendocrine disturbances characterizing diabetic encephalopathy (Rajashree et al., 2011). For instance, diabetes-induced cerebellar dysfunction ∗ Corresponding author. Tel.: +20 1015406365. E-mail addresses: gehanakabawy@gmail.com (G. El-Akabawy), wael elkholy71@yahoo.com (W. El-Kholy). is associated with seizure generation, motor deficits, and mem- ory impairment (Anu et al., 2010). Defects in hippocampal synaptic plasticity and transmission result in deterioration of learning and memory in diabetic patients (Shingo et al., 2012). Interestingly, accumulating recent evidence indicates that diabetes mellitus is an important risk factor for sporadic Alzheimer’s disease (AD) (Vignini et al., 2013). One of the underlying mechanisms of diabetic neuronal injury is the excessive free radical generation from the auto-oxidation of elevated intracellular glucose levels (Gradinaru et al., 2013). Indeed, several in vitro, experimental, and clinical studies have implicated oxidative stress in the pathogenesis of diabetic com- plications. Oxidative stress results in depolarization of the inner mitochondrial membrane, release of cytochrome c into the cytosol, and ultimately, induction of caspase mediated apoptosis (Gurpinar et al., 2012). Ginger (Zingiber officinale) is widely consumed as a spice for the flavoring of foods. Ginger is reported to have several beneficial pharmacological effects (hypoglycemic, insulinotropic, and hypolipidemic) in experimental animals (Shanmugam et al., 2011) and in humans (Huang et al., 2004). It has been documented that ginger or its extracts possess some pharmacological activities including analgesic (Young et al., 2005), anti-tumor (Habib et al., http://dx.doi.org/10.1016/j.aanat.2014.01.003 0940-9602/© 2014 Elsevier GmbH. All rights reserved.