Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain
| Autor: | Alexandre Boutigny, Leslie Schwendimann, Nassim Mohamedi, Tania Vitalis, Philippe Bonnin, Christiane Charriaut-Marlangue, Valérie C. Besson |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Male medicine.medical_specialty QH301-705.5 Ischemia Hemodynamics Brain damage Poly(ADP-ribose) Polymerase Inhibitors Blood–brain barrier neonatal ischemia Microbiology Permeability Brain Ischemia Lesion Mice Internal medicine medicine Animals collateral circulation Biology (General) Molecular Biology Stroke doppler ultrasonography business.industry Brain Ultrasonography Doppler General Medicine Phenanthrenes medicine.disease somatostatin receptor Mice Inbred C57BL medicine.anatomical_structure Endocrinology Phenotype Cerebral blood flow Animals Newborn Blood-Brain Barrier Astrocytes cardiovascular system Female Microglia medicine.symptom business octreotide Carotid Artery Internal Astrocyte |
| Zdroj: | Current Issues in Molecular Biology, Vol 43, Iss 25, Pp 301-312 (2021) Current Issues in Molecular Biology Volume 43 Issue 1 Pages 25-312 |
| ISSN: | 1467-3045 |
| Popis: | The poly(ADP-ribose) polymerase inhibitor PJ34 has recently been reported to increase cerebral blood flow, via the endothelial NO synthase, in the naive mouse brain throughout life. We addressed here the benefits of PJ34 after neonatal ischemia on hemodynamics and components of the neurovascular unit including the blood-brain barrier (BBB), microglia, and astrocytes. Nine-day-old mice were subjected to permanent MCA occlusion (pMCAo), and treated with either PBS or PJ34 (10 mg/kg). Mean blood-flow velocities (mBFV) were measured in both internal carotid arteries (ICA) and basilar trunk (BT) using Doppler-ultrasonography. BBB opening was assessed through somatostatin-receptor type-2 internalization and immunohistochemistry at 24 and 48 h. Lesion areas were measured 8 days after ischemia. In PBS-treated mice, pMCAo involved a drop in mBFV in the left ICA (p < 0.001 vs. basal), whereas mBFV remained stable in both right ICA and BT. PJ34 prevented this drop in the left ICA (NS vs. basal) and increased mBFV in the right ICA (p = 0.0038 vs. basal). No modification was observed in the BT. In contrast to PBS, BBB disruption extent and astrocyte demise were reduced in PJ34 mice only in the rostral brain at 48 h and 8 days post-pMCAo, respectively. Accordingly, 8 days after pMCAo, affected areas were reduced in the rostral brain (Bregma +0.86 and +0.14 mm), whereas total tissue loss was not reduced after PJ34 (4.0 ± 3.1%) vs. PBS (5.8 ± 3.4%). These results show that PJ34 reduced BBB permeability, astrocyte demise, and tissue loss (particularly in the rostral territories), suggesting that collateral supply mainly proceeds from the anterior ICA’s branches in the ischemic neonatal mouse brain. |
| Databáze: | OpenAIRE |
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