Inhibition of poly(ADP-ribose) polymerase activity protects hippocampal cells against morphological and ultrastructural alteration evoked by ischemia-reperfusion injury
Journal Title: Folia Neuropathologica - Year 2005, Vol 43, Issue 3
Abstract
Poly(ADP-ribose) polymerase 1 (PARP-1 EC 2.4.2.30) is a nuclear enzyme that plays an important role in cell survival and death. PARP is involved in DNA repair machinery, however, massive DNA damage leads to overactivation of PARP-1 and to depletion of its substrate bNAD+ which causes cell death. Our previous study indicated that the PARP activity was significantly activated during ischemia-reperfusion injury. In this study we investigated the effect of PARP inhibitor, 3-aminobenzamide (3-AB) on intracellular organelles alteration. Gerbils were submitted to 3 and 10 min transient global ischemia followed by recirculation and survival for 1 till 7 days. The histological and electron microscopic examination indicated a pronounced protective effect of 3-AB on the swelling of astrocytes and neurons 1 day after 3 and 10 min ischemic insult. It decreased also the swelling of pericytes. 3-AB decreases evoked by ischemia swelling of mitochondria and Golgi apparatus. The significant ameliorating effect of 3-AB was also observed on the 7th day of reperfusion after 3 min ischemia and was also visible on the 1st day after 10 min ischemia. However, 7 days after prolonged 10 min ischemia almost all neurons in the CA1 hippocampal layer died and 3-AB was not able to protect these cells. In spite of that, 3-AB markedly decreased immunostaining of glial fibrillary acidic protein (GFAP), which was enhanced in the stratum: oriens, radiatum and lacunosum-moleculare at the 7th day after 10 min ischemia. These data indicated that inhibition of PARP may have a protective effect on neuronal cells affected by ischemia-reperfusion injury.
Authors and Affiliations
Robert Strosznajder, Roman Gadamski, Michał Walski
Keywords
Related Articles
- EP ID EP101936
- DOI -
- Views 86
- Downloads 0
Risks of transmission of variant Creutzfeldt-Jakob disease by blood transfusion
Variant Creutzfeldt-Jakob disease (vCJD) was first identified in 1996 in the UK, and results from human exposure to the bovine spongiform encephalopathy (BSE) agent. vCJD has subsequently been identified in 10 additional...
Plaques and tangles and the pathogenesis of Alzheimer’s disease
Since the earliest descriptions, senile plaques (SP) and neurofibrillary tangles (NFT) have been regarded as the pathological hallmarks of Alzheimer’s disease (AD). Consequently, studies of the morphology, distribution...
The role of excitotoxicity in neurodegeneration
A body of evidence suggests that the mechanisms of excitotoxic neuronal damage evoked by excessive or prolonged activation of the excitatory amino acid receptors may be involved in pathogenesis of brain damage in acute i...
Is there a spatial association between senile plaques and neurofibrillary tangles in Alzheimer’s disease?
Obective: To test the hypothesis that the clusters of senile plaques (SP) and neurofibrillary tangles (NFT) in patients with Alzheimer's disease (AD) are spatially associated as predicted by the 'Amyloid Cascade Hypoth...
Abstracts