Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats

Gábor Lenzsér, Béla Kis, James A. Snipes, Tamás Gáspár, Péter Sándor, Katalin Komjáti, Csaba Szabo, David W. Busija

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays a significant role in postischemic brain injury. We assessed the contribution of PARP activation to the blood-brain barrier (BBB) disruption and edema formation after ischemia-reperfusion. In male Wistar rats, global cerebral ischemia was achieved by occluding the carotid arteries and lowering arterial blood pressure for 20 mins. The animals were treated with saline or with the PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl (PJ34); (10 mg/kg, i.v.) before ischemia. After 40 mins, 24, and 48 h of reperfusion, the permeability of the cortical BBB was determined after Evans Blue (EB) and Na-fluorescein (NaF) administration. The water content of the brain was also measured. The permeability of the BBB for EB increased after ischemia-reperfusion compared with the nonischemic animals after 24 and 48 h reperfusion but PARP inhibition attenuated this increase at 48 h (nonischemic: 170±9, saline: 760±95, PJ34: 472±61 ng/mg tissue). The extravasation of NaF showed similar changes and PJ34 post-treatment attenuated the permeability increase even at 24 h. PARP inhibition decreased the brain edema seen at 48 h. Because PARP has proinflammatory properties, the neutrophil infiltration of the cortex was determined, which showed lower values after PJ34 treatment. Furthermore, PJ34 treatment decreased the loss of the tight junction protein occludin at 24 and 48 h. The inhibition of PARP activity accompanied by reduced post-ischemic BBB disturbance and decreased edema formation suggests a significant role of this enzyme in the development of cerebral vascular malfunction.

Original languageEnglish (US)
Pages (from-to)1318-1326
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue number7
DOIs
StatePublished - Jul 27 2007
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
Blood-Brain Barrier
Reperfusion
Permeability
Evans Blue
Ischemia
Fluorescein
Edema
Occludin
Tight Junction Proteins
Neutrophil Infiltration
Brain Edema
Enzymes
Brain Ischemia
Carotid Arteries
Brain Injuries
Blood Vessels
Wistar Rats
Arterial Pressure
Oxidative Stress

Keywords

  • Blood-brain barrier
  • Brain edema
  • Ischemia-reperfusion
  • Occludin
  • PJ34
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Lenzsér, G., Kis, B., Snipes, J. A., Gáspár, T., Sándor, P., Komjáti, K., ... Busija, D. W. (2007). Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats. Journal of Cerebral Blood Flow and Metabolism, 27(7), 1318-1326. https://doi.org/10.1038/sj.jcbfm.9600437

Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats. / Lenzsér, Gábor; Kis, Béla; Snipes, James A.; Gáspár, Tamás; Sándor, Péter; Komjáti, Katalin; Szabo, Csaba; Busija, David W.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. 7, 27.07.2007, p. 1318-1326.

Research output: Contribution to journalArticle

Lenzsér, G, Kis, B, Snipes, JA, Gáspár, T, Sándor, P, Komjáti, K, Szabo, C & Busija, DW 2007, 'Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats', Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 7, pp. 1318-1326. https://doi.org/10.1038/sj.jcbfm.9600437
Lenzsér, Gábor ; Kis, Béla ; Snipes, James A. ; Gáspár, Tamás ; Sándor, Péter ; Komjáti, Katalin ; Szabo, Csaba ; Busija, David W. / Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats. In: Journal of Cerebral Blood Flow and Metabolism. 2007 ; Vol. 27, No. 7. pp. 1318-1326.
@article{f04e54191b2b42a39e0fa183cfc2c137,
title = "Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats",
abstract = "The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays a significant role in postischemic brain injury. We assessed the contribution of PARP activation to the blood-brain barrier (BBB) disruption and edema formation after ischemia-reperfusion. In male Wistar rats, global cerebral ischemia was achieved by occluding the carotid arteries and lowering arterial blood pressure for 20 mins. The animals were treated with saline or with the PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl (PJ34); (10 mg/kg, i.v.) before ischemia. After 40 mins, 24, and 48 h of reperfusion, the permeability of the cortical BBB was determined after Evans Blue (EB) and Na-fluorescein (NaF) administration. The water content of the brain was also measured. The permeability of the BBB for EB increased after ischemia-reperfusion compared with the nonischemic animals after 24 and 48 h reperfusion but PARP inhibition attenuated this increase at 48 h (nonischemic: 170±9, saline: 760±95, PJ34: 472±61 ng/mg tissue). The extravasation of NaF showed similar changes and PJ34 post-treatment attenuated the permeability increase even at 24 h. PARP inhibition decreased the brain edema seen at 48 h. Because PARP has proinflammatory properties, the neutrophil infiltration of the cortex was determined, which showed lower values after PJ34 treatment. Furthermore, PJ34 treatment decreased the loss of the tight junction protein occludin at 24 and 48 h. The inhibition of PARP activity accompanied by reduced post-ischemic BBB disturbance and decreased edema formation suggests a significant role of this enzyme in the development of cerebral vascular malfunction.",
keywords = "Blood-brain barrier, Brain edema, Ischemia-reperfusion, Occludin, PJ34, Poly(ADP-ribose) polymerase",
author = "G{\'a}bor Lenzs{\'e}r and B{\'e}la Kis and Snipes, {James A.} and Tam{\'a}s G{\'a}sp{\'a}r and P{\'e}ter S{\'a}ndor and Katalin Komj{\'a}ti and Csaba Szabo and Busija, {David W.}",
year = "2007",
month = "7",
day = "27",
doi = "10.1038/sj.jcbfm.9600437",
language = "English (US)",
volume = "27",
pages = "1318--1326",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats

AU - Lenzsér, Gábor

AU - Kis, Béla

AU - Snipes, James A.

AU - Gáspár, Tamás

AU - Sándor, Péter

AU - Komjáti, Katalin

AU - Szabo, Csaba

AU - Busija, David W.

PY - 2007/7/27

Y1 - 2007/7/27

N2 - The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays a significant role in postischemic brain injury. We assessed the contribution of PARP activation to the blood-brain barrier (BBB) disruption and edema formation after ischemia-reperfusion. In male Wistar rats, global cerebral ischemia was achieved by occluding the carotid arteries and lowering arterial blood pressure for 20 mins. The animals were treated with saline or with the PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl (PJ34); (10 mg/kg, i.v.) before ischemia. After 40 mins, 24, and 48 h of reperfusion, the permeability of the cortical BBB was determined after Evans Blue (EB) and Na-fluorescein (NaF) administration. The water content of the brain was also measured. The permeability of the BBB for EB increased after ischemia-reperfusion compared with the nonischemic animals after 24 and 48 h reperfusion but PARP inhibition attenuated this increase at 48 h (nonischemic: 170±9, saline: 760±95, PJ34: 472±61 ng/mg tissue). The extravasation of NaF showed similar changes and PJ34 post-treatment attenuated the permeability increase even at 24 h. PARP inhibition decreased the brain edema seen at 48 h. Because PARP has proinflammatory properties, the neutrophil infiltration of the cortex was determined, which showed lower values after PJ34 treatment. Furthermore, PJ34 treatment decreased the loss of the tight junction protein occludin at 24 and 48 h. The inhibition of PARP activity accompanied by reduced post-ischemic BBB disturbance and decreased edema formation suggests a significant role of this enzyme in the development of cerebral vascular malfunction.

AB - The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays a significant role in postischemic brain injury. We assessed the contribution of PARP activation to the blood-brain barrier (BBB) disruption and edema formation after ischemia-reperfusion. In male Wistar rats, global cerebral ischemia was achieved by occluding the carotid arteries and lowering arterial blood pressure for 20 mins. The animals were treated with saline or with the PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl (PJ34); (10 mg/kg, i.v.) before ischemia. After 40 mins, 24, and 48 h of reperfusion, the permeability of the cortical BBB was determined after Evans Blue (EB) and Na-fluorescein (NaF) administration. The water content of the brain was also measured. The permeability of the BBB for EB increased after ischemia-reperfusion compared with the nonischemic animals after 24 and 48 h reperfusion but PARP inhibition attenuated this increase at 48 h (nonischemic: 170±9, saline: 760±95, PJ34: 472±61 ng/mg tissue). The extravasation of NaF showed similar changes and PJ34 post-treatment attenuated the permeability increase even at 24 h. PARP inhibition decreased the brain edema seen at 48 h. Because PARP has proinflammatory properties, the neutrophil infiltration of the cortex was determined, which showed lower values after PJ34 treatment. Furthermore, PJ34 treatment decreased the loss of the tight junction protein occludin at 24 and 48 h. The inhibition of PARP activity accompanied by reduced post-ischemic BBB disturbance and decreased edema formation suggests a significant role of this enzyme in the development of cerebral vascular malfunction.

KW - Blood-brain barrier

KW - Brain edema

KW - Ischemia-reperfusion

KW - Occludin

KW - PJ34

KW - Poly(ADP-ribose) polymerase

UR - http://www.scopus.com/inward/record.url?scp=34250792144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250792144&partnerID=8YFLogxK

U2 - 10.1038/sj.jcbfm.9600437

DO - 10.1038/sj.jcbfm.9600437

M3 - Article

C2 - 17213862

AN - SCOPUS:34250792144

VL - 27

SP - 1318

EP - 1326

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 7

ER -