Tags

Type your tag names separated by a space and hit enter

Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats.
Pediatr Res. 2005 Apr; 57(4):481-7.PR

Abstract

Erythropoietin (Epo) plays a central role in erythropoiesis but also has neuroprotective properties. Recently, Epo-related neuroprotective studies used a hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent cause of neonatal brain injury. We report on the effects of Epo treatment given after focal stroke and its potential neuroprotective mechanisms in postnatal day 7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle cerebral artery. The experimental groups included sham operation, FCI plus vehicle, and FCI plus Epo. In the Epo-treated group, pups received a single intraperitoneal injection of 1000 U/kg 15 min after FCI or three injections of 100, 1000, or 5000 U/kg, starting at 15 min and repeated at 1 and 2 d after FCI. Epo treatment produced significant reductions in the mean infarct area and volume at 1 and 3 d after FCI, demonstrated by 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining showed a markedly reduced number of TUNEL-positive cells in the Epo-treated group when compared with the vehicle control 3 d after FCI (p<0.01). The most effective dose after FCI was 1000 U/kg for 3 d. Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-kappaB expression. In conclusion, Epo given after FCI in neonatal rats provides significant neuroprotection, mediated possibly by activation of the Janus kinase-signal transducer and activator of transcription-Bcl-xL signaling pathways.

Authors+Show Affiliations

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15718373

Citation

Sola, Augusto, et al. "Erythropoietin After Focal Cerebral Ischemia Activates the Janus Kinase-signal Transducer and Activator of Transcription Signaling Pathway and Improves Brain Injury in Postnatal Day 7 Rats." Pediatric Research, vol. 57, no. 4, 2005, pp. 481-7.
Sola A, Rogido M, Lee BH, et al. Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Pediatr Res. 2005;57(4):481-7.
Sola, A., Rogido, M., Lee, B. H., Genetta, T., & Wen, T. C. (2005). Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Pediatric Research, 57(4), 481-7.
Sola A, et al. Erythropoietin After Focal Cerebral Ischemia Activates the Janus Kinase-signal Transducer and Activator of Transcription Signaling Pathway and Improves Brain Injury in Postnatal Day 7 Rats. Pediatr Res. 2005;57(4):481-7. PubMed PMID: 15718373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. AU - Sola,Augusto, AU - Rogido,Marta, AU - Lee,Ben H, AU - Genetta,Tom, AU - Wen,Tong-Chun, Y1 - 2005/02/17/ PY - 2005/2/19/pubmed PY - 2005/9/21/medline PY - 2005/2/19/entrez SP - 481 EP - 7 JF - Pediatric research JO - Pediatr Res VL - 57 IS - 4 N2 - Erythropoietin (Epo) plays a central role in erythropoiesis but also has neuroprotective properties. Recently, Epo-related neuroprotective studies used a hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent cause of neonatal brain injury. We report on the effects of Epo treatment given after focal stroke and its potential neuroprotective mechanisms in postnatal day 7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle cerebral artery. The experimental groups included sham operation, FCI plus vehicle, and FCI plus Epo. In the Epo-treated group, pups received a single intraperitoneal injection of 1000 U/kg 15 min after FCI or three injections of 100, 1000, or 5000 U/kg, starting at 15 min and repeated at 1 and 2 d after FCI. Epo treatment produced significant reductions in the mean infarct area and volume at 1 and 3 d after FCI, demonstrated by 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining showed a markedly reduced number of TUNEL-positive cells in the Epo-treated group when compared with the vehicle control 3 d after FCI (p<0.01). The most effective dose after FCI was 1000 U/kg for 3 d. Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-kappaB expression. In conclusion, Epo given after FCI in neonatal rats provides significant neuroprotection, mediated possibly by activation of the Janus kinase-signal transducer and activator of transcription-Bcl-xL signaling pathways. SN - 0031-3998 UR - https://www.unboundmedicine.com/medline/citation/15718373/Erythropoietin_after_focal_cerebral_ischemia_activates_the_Janus_kinase_signal_transducer_and_activator_of_transcription_signaling_pathway_and_improves_brain_injury_in_postnatal_day_7_rats_ L2 - https://doi.org/10.1203/01.PDR.0000155760.88664.06 DB - PRIME DP - Unbound Medicine ER -