Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain

被引:5
|
作者
Bonnin, Philippe [1 ]
Vitalis, Tania [2 ]
Schwendimann, Leslie [2 ]
Boutigny, Alexandre [1 ]
Mohamedi, Nassim [1 ]
Besson, Valerie C. [3 ]
Charriaut-Marlangue, Christiane [2 ]
机构
[1] Univ Paris, Hop Lariboisiere, Physiol Clin Explorat Fonctionnelles, U1148,LVTS,INSERM, F-75010 Paris, France
[2] Univ Paris, Hop Robert Debre, INSERM, U1141 NeuroDiderot, F-75019 Paris, France
[3] Univ Paris, Fac Pharm Paris, UMR S1144, Optimisat Therapeut Neuropsychopharmacol, F-75006 Paris, France
关键词
neonatal ischemia; doppler ultrasonography; collateral circulation; blood-brain barrier; somatostatin receptor; octreotide; astrocytes; ENDOTHELIAL DYSFUNCTION; CEREBRAL-ISCHEMIA; RAT; INFLAMMATION; RESPONSES; DEATH;
D O I
10.3390/cimb43010025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:301 / 312
页数:12
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