RGD Reference Report - Cerebral endothelial expression of Robo1 affects brain infiltration of polymorphonuclear neutrophils during mouse stroke recovery. - Rat Genome Database

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Cerebral endothelial expression of Robo1 affects brain infiltration of polymorphonuclear neutrophils during mouse stroke recovery.

Authors: Gangaraju, Sandhya  Sultan, Khadeejah  Whitehead, Shawn N  Nilchi, Ladan  Slinn, Jacqueline  Li, Xuesheng  Hou, Sheng T 
Citation: Gangaraju S, etal., Neurobiol Dis. 2013 Jun;54:24-31. doi: 10.1016/j.nbd.2013.02.014. Epub 2013 Mar 5.
RGD ID: 243048431
Pubmed: PMID:23473743   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nbd.2013.02.014   (Journal Full-text)

Increased brain infiltration of polymorphonuclear neutrophils (PMNs) occurs early after stroke and is important in eliciting brain inflammatory response during stroke recovery. In order to understand the molecular mechanism of PMN entry, we investigated the expression and requirement for Slit1, a chemorepulsive guidance cue, and its cognate receptor, Robo1, in a long-term recovery mouse model of cerebral ischemia. The expression levels of Robo1 were significantly decreased bilaterally at 24h following reperfusion. Robo1 expression levels remained suppressed in the ipsilateral cortex until 28d post MCAO-reperfusion, while the levels of Robo1 in the contralateral cortex recovered to the level of sham-operated mouse by 7d reperfusion. Circulating PMNs express high levels of Slit1, but not Robo1. Influx of PMNs into the ischemic core area occurred early (24h) after cerebral ischemia, when endothelial Robo1 expression was significantly reduced in the ischemic brain, indicating that Robo1 may form a repulsive barrier to PMN entry into the brain parenchyma. Indeed, blocking Slit1 on PMNs in a transwell migration assay in combination with an antibody blocking of Robo1 on human umbilical vein endothelial cells (HUVEC) significantly increased PMN transmigration during oxygen glucose deprivation, an in vitro model of ischemia. Collectively, in the normal brain, the presence of Slit1 on PMNs, and Robo1 on cerebral endothelial cells, generated a repulsive force to prevent the infiltration of PMNs into the brain. During stroke recovery, a transient reduction in Robo1 expression on the cerebral endothelial cells allowed the uncontrolled infiltration of Slit1-expressing PMNs into the brain causing inflammatory reactions.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia disease_progressionISORobo1 (Mus musculus)243048431; 243048431 RGD 
transient cerebral ischemia disease_progressionIEP 243048431 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Robo1  (roundabout guidance receptor 1)

Genes (Mus musculus)
Robo1  (roundabout guidance receptor 1)

Genes (Homo sapiens)
ROBO1  (roundabout guidance receptor 1)


Additional Information