The Anti-Inflammatory and Neuroprotective Effects of Ghrelin in Subarachnoid Hemorrhage-Induced Oxidative Brain Damage in Rats

Abstract

To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)-induced brain injury, Wistar albino rats (n = 54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 μg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100β protein, TNF-α, and IL-1β levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na⁺-K⁺-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood–brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na⁺-K⁺-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100β, TNF-α, and IL-1β in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.