Evidence map›Paper›PMID 26550694›Full record

ArticleNeurobiology of disease2016

Recombinant Slit2 attenuates neuroinflammation after surgical brain injury by inhibiting peripheral immune cell infiltration via Robo1-srGAP1 pathway in a rat model.

Prativa Sherchan, Lei Huang, Yuechun Wang, Onat Akyol, Jiping Tang, John H Zhang

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. SLIT2 as a key regulator and therapeutic target in liver injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  7. Unraveling Axon Guidance during Axotomy and Regeneration.International journal of molecular sciences · 2021
    Review
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  12. The Activation of Phosphatidylserine/CD36/TGF-Oxidative medicine and cellular longevity · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Surgically-induced brain injury: where are we now?Chinese neurosurgical journal · 2019
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Prativa SherchanDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, U.S.A.
Lei HuangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, U.S.A.; Department of Anesthesiology, Loma Linda University, CA 92354, U.S.A.
Yuechun WangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, U.S.A.
Onat AkyolDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, U.S.A.
Jiping TangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, U.S.A.
John H ZhangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, U.S.A.; Department of Anesthesiology, Loma Linda University, CA 92354, U.S.A.; Department of Neurosurgery, Loma Linda University, CA 92354, U.S.A.. Electronic address: johnzhang3910@yahoo.com.
Loma Linda University · US

Funding

Crotalus Snake Venom Preconditioning to Prevent Surgical Brain InjuryR01NS084921 · NINDS · LOMA LINDA UNIVERSITY · PI ZHANG, JOHN H · 2014 to 2018
$1.7M
NINDS NIH HHS R01 NS084921
6 · The paper itself

Abstract

background and purposePeripheral immune cell infiltration to the brain tissue at the perisurgical site can promote neuroinflammation after surgical brain injury (SBI). Slit2, an extracellular matrix protein, has been reported to reduce leukocyte migration. This study evaluated the effect of recombinant Slit2 and the role of its receptor roundabout1 (Robo1) and its downstream mediator Slit-Robo GTPase activating protein 1 (srGAP1)-Cdc42 on peripheral immune cell infiltration after SBI in a rat model.

methodsOne hundred and fifty-three adult male Sprague-Dawley rats (280-350 g) were used. Partial resection of right frontal lobe was performed to induce SBI. Slit2 siRNA was administered by intracerebroventricular injection 24h before SBI. Recombinant Slit2 was injected intraperitoneally 1h before SBI. Recombinant Robo1 used as a decoy receptor was co-administered with recombinant Slit2. srGAP1 siRNA was administered by intracerebroventricular injection 24h before SBI. Post-assessments included brain water content measurement, neurological tests, ELISA, Western blot, immunohistochemistry, and Cdc42 activity assay.

resultsEndogenous Slit2 was increased after SBI. Robo1 was expressed by peripheral immune cells. Endogenous Slit2 knockdown worsened brain edema after SBI. Recombinant Slit2 administration reduced brain edema, neurological deficits, and pro-inflammatory cytokines after SBI. Recombinant Slit2 reduced peripheral immune cell markers cluster of differentiation 45 (CD45) and myeloperoxidase (MPO), as well as Cdc42 activity in the perisurgical brain tissue which was reversed by recombinant Robo1 co-administration and srGAP1 siRNA.

conclusionsRecombinant Slit2 improved outcomes by reducing neuroinflammation after SBI, possibly by decreasing peripheral immune cell infiltration to the perisurgical site through Robo1-srGAP1 mediated inhibition of Cdc42 activity. These results suggest that Slit2 may be beneficial to reduce SBI-induced neuroinflammation.

Indexed as

AnimalsBrain EdemaBrain InjuriesDisease Models, AnimalFrontal LobeGene Knockdown TechniquesGenetic TherapyGTPase-Activating ProteinsInfusions, IntraventricularIntercellular Signaling Peptides and ProteinsIntraoperative ComplicationsMaleNerve Tissue ProteinsRats, Sprague-DawleyReceptors, ImmunologicRecombinant ProteinsGTPase-Activating ProteinsIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsReceptors, ImmunologicRecombinant ProteinsRoundabout ProteinsSlit Homolog 2 ProteintGAP1 protein, ratBrain edemaCdc42NeuroinflammationPeripheral immune cell infiltrationRobo1Slit2srGAP1Surgical brain injury

Identifiers

PMID26550694
PMCPMC4688150
OpenAlexW2193253393

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.