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The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia.
Neurosci Lett. 2006 May 08; 398(3):300-5.NL

Abstract

The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment 1, a dose of 0.2 mg/kg inhibited proteasome activity by 77% and infarct volume was reduced to 175.7+/-59.9 mm3 and 205.9+/-83.9 mm3 (1 and 2 h group, respectively; p<0.05) compared to 306.5+/-48.5 mm3 (control). Treatment at 3 h was not neuroprotective (293.0+/-40.1 mm3). After embolic MCAO, infarct volume was 167.5+/-90.7 mm3 (treatment group) and 398.9+/-141.3 mm3 (control; p=0.002). In conclusion, VELCADE treatment inhibited whole blood proteasome activity and achieved significant neuroprotection in two rat models of focal cerebral ischemia at various time points poststroke.

Authors+Show Affiliations

Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Nils.Henninger@umassmed.eduNo 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

16490315

Citation

Henninger, Nils, et al. "The Proteasome Inhibitor VELCADE Reduces Infarction in Rat Models of Focal Cerebral Ischemia." Neuroscience Letters, vol. 398, no. 3, 2006, pp. 300-5.
Henninger N, Sicard KM, Bouley J, et al. The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia. Neurosci Lett. 2006;398(3):300-5.
Henninger, N., Sicard, K. M., Bouley, J., Fisher, M., & Stagliano, N. E. (2006). The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia. Neuroscience Letters, 398(3), 300-5.
Henninger N, et al. The Proteasome Inhibitor VELCADE Reduces Infarction in Rat Models of Focal Cerebral Ischemia. Neurosci Lett. 2006 May 8;398(3):300-5. PubMed PMID: 16490315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia. AU - Henninger,Nils, AU - Sicard,Kenneth M, AU - Bouley,James, AU - Fisher,Marc, AU - Stagliano,Nancy E, Y1 - 2006/02/21/ PY - 2005/11/11/received PY - 2006/01/05/revised PY - 2006/01/09/accepted PY - 2006/2/24/pubmed PY - 2006/6/9/medline PY - 2006/2/24/entrez SP - 300 EP - 5 JF - Neuroscience letters JO - Neurosci. Lett. VL - 398 IS - 3 N2 - The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment 1, a dose of 0.2 mg/kg inhibited proteasome activity by 77% and infarct volume was reduced to 175.7+/-59.9 mm3 and 205.9+/-83.9 mm3 (1 and 2 h group, respectively; p<0.05) compared to 306.5+/-48.5 mm3 (control). Treatment at 3 h was not neuroprotective (293.0+/-40.1 mm3). After embolic MCAO, infarct volume was 167.5+/-90.7 mm3 (treatment group) and 398.9+/-141.3 mm3 (control; p=0.002). In conclusion, VELCADE treatment inhibited whole blood proteasome activity and achieved significant neuroprotection in two rat models of focal cerebral ischemia at various time points poststroke. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/16490315/The_proteasome_inhibitor_VELCADE_reduces_infarction_in_rat_models_of_focal_cerebral_ischemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(06)00027-9 DB - PRIME DP - Unbound Medicine ER -