RGD Reference Report - Inhibition of sonic hedgehog signaling aggravates brain damage associated with the down-regulation of Gli1, Ptch1 and SOD1 expression in acute ischemic stroke. - Rat Genome Database

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Inhibition of sonic hedgehog signaling aggravates brain damage associated with the down-regulation of Gli1, Ptch1 and SOD1 expression in acute ischemic stroke.

Authors: Ji, H  Miao, J  Zhang, X  Du, Y  Liu, H  Li, S  Li, L 
Citation: Ji H, etal., Neurosci Lett. 2012 Jan 6;506(1):1-6. doi: 10.1016/j.neulet.2011.11.027. Epub 2011 Nov 25.
RGD ID: 8657023
Pubmed: PMID:22133807   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neulet.2011.11.027   (Journal Full-text)

Oxidative and cytotoxic damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Recent studies have indicated that sonic hedgehog (Shh) signaling could protect neurons against oxidative stress by increasing superoxide dismutase 1 (SOD1) activity. Glioma-associated oncogene homolog 1 (Gli1) and patched-1 (Ptch1) are both components and transcriptional targets of the Shh pathway. Here, we designed this study to determine the effect of inhibition of Shh pathway on the development of cerebral ischemia injury. Male, Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO). Cyclopamine (0.18mg/kg), the classical inhibitor of Shh signaling, was stereotactic injected into the lateral cerebral ventricle immediately after pMCAO. At 24h neurological deficit was evaluated using a modified six point scale; brain water content was measured; infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC). Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), Western Blotting and activity assay were used to analyze the expression of Gli1, Ptch1 and SOD1. Compared with Vehicle group, cyclopamine down-regulated Gli1, Ptch1 and SOD1 in pMCAO-affected brain tissue (P<0.05), and increased infarct volume (P<0.05), brain water content (P<0.05) and behavioral deficits (P<0.05). Collectively, the present results suggest that inhibition of Shh signaling pathway exacerbated rat ischemic damage caused by pMCAO, which may be correlated with down-regulated expression of Gli1, Ptch1 and SOD1.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
middle cerebral artery infarction  ISOSod1 (Rattus norvegicus)8657023; 8657023mRNA and protein:increased expression:cerebral cortex (rat)RGD 
middle cerebral artery infarction  IEP 8657023mRNA and protein:increased expression:cerebral cortex (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Genes (Mus musculus)
Sod1  (superoxide dismutase 1, soluble)

Genes (Homo sapiens)
SOD1  (superoxide dismutase 1)


Additional Information