The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats.

Ersahin M., Toklu H. Z., ERZİK C., ÇETİNEL Ş., AKAKIN D., VELİOĞLU ÖĞÜNÇ A., ...More

Journal of neurotrauma, vol.27, no.6, pp.1143-55, 2010 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 6
  • Publication Date: 2010
  • Doi Number: 10.1089/neu.2009.1210
  • Journal Name: Journal of neurotrauma
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1143-55
  • Keywords: cerebral vasospasm, ghrelin, lipid peroxidation, neuron-specific enolase, oxidative stress, subarachnoid hemorrhage, S-100 beta, NEURON-SPECIFIC ENOLASE, REMOTE ORGAN INJURY, CEREBRAL VASOSPASM, CEREBROSPINAL-FLUID, HEAD-INJURY, ISCHEMIA-REPERFUSION, RADICAL SCAVENGER, ACYLATED PEPTIDE, REACTIVE OXYGEN, PROTEIN S-100B
  • Marmara University Affiliated: Yes

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 mu g/kg/d IP) SAH groups. The rats were injected with blood (0.3mL) 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-100 beta protein, TNF-alpha, and IL-1 beta 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-100 beta, TNF-alpha, and IL-1 beta 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.