Premium
Contribution of poly(ADP‐ribose) polymerase (PARP) to post‐ischemic blood‐brain barrier (BBB) damage in rats
Author(s) -
Lenzsér Gábor,
Snipes James A.,
Kis Béla,
Gáspár Tamás,
Sándor Péter,
Komjáti Katalin,
Szabó Csaba,
Busija David W.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1157
Subject(s) - evans blue , occludin , extravasation , poly adp ribose polymerase , parp inhibitor , blood–brain barrier , ischemia , chemistry , tight junction , oxidative stress , infiltration (hvac) , pharmacology , endocrinology , anesthesia , medicine , pathology , biochemistry , central nervous system , enzyme , polymerase , physics , thermodynamics
The nuclear enzyme PARP is activated by oxidative stress and it plays a significant role in post‐ischemic brain injury. In our experiments we assessed the contribution of PARP activation to the BBB disruption and edema formation after cerebral ischemia‐reperfusion (I/R). In male Wistar rats global cerebral ischemia was achieved by clipping the carotid arteries and lowering arterial blood pressure for 20 min. The animals were treated with saline (S) or with the PARP inhibitor PJ‐34 (iv. 10mg/kg) before ischemia. After 48 h of reperfusion the permeability of the BBB of the cortex was determined by Evans‐blue (EB) and Na‐fluorescein (NaF) administration. The water content of the brain was measured as well. The permeability of the BBB for EB increased after I/R compared to the non‐ischemic (NI) animals but it was decreased by PARP inhibition (NI: 176±15 (n=5), S: 773±97 (n=12), PJ‐34: 479±62 (n=12) ng/mg tissue). The extravasation of NaF and brain water content showed similar changes. Since PARP has proinflammatory properties, the neutrophil infiltration of the cortex was determined (myeloperoxidase assay), which showed lower values in the treated animals. Furthermore, PJ‐34 treatment decreased the loss of the tight junction protein occludin. The inhibition of PARP activity was accompanied by reduced post‐ischemic BBB disturbance and decreased edema formation suggesting a significant role of the enzyme in the development of the vascular malfunction. NIH grants: HL‐50587, HL‐65380, HL‐77731