Leger P L, Bonnin P, Moretti R, Tanaka S, Duranteau J, Renolleau S, Baud O, Charriaut-Marlangue C
Universitx00E9; Paris Diderot, Sorbonne Paris Citx00E9;, INSERM UMR 1141, Paris, France.
Cerebrovasc Dis. 2016;41(1-2):40-9. doi: 10.1159/000441663. Epub 2015 Nov 25.
The development of collateral circulation is proposed as an inherent compensatory mechanism to restore impaired blood perfusion after ischemia, at least in the penumbra. We have studied the dynamic macro- and microcirculation after ischemia-reperfusion in the juvenile rat brain and evaluated the impact of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow.
Fourteen-day-old (P14) rats were subjected to ischemia-reperfusion and treated with either PBS or 7-nitroindazole (7-NI, an nNOS inhibitor, 25 mg/kg). Arterial blood flow (BF) was measured using 2D-color-coded pulsed ultrasound imaging. Laser speckle contrast (LSC) imaging and sidestream dark-field videomicroscopy were used to measure cortical and microvascular BF, respectively.
In basal conditions, 7-NI reduced BF in the internal carotids (by ∼ 25%) and cortical (by ∼ 30%) BF, as compared to PBS. During ischemia, the increased mean BF velocity in the basilar trunk after both PBS and 7-NI demonstrated the establishment of collateral support and patency. Upon re-flow, BF immediately recovered to basal values in the internal carotid arteries under both conditions. The 7-NI group showed increased collateral flow in the penumbral tissue during early re-flow compared to PBS, as shown with both LSC imaging and side-stream dark-field videomicroscopy. The proportion of perfused capillaries was significantly increased under 7-NI as compared to PBS when given before ischemia (67.0 ± 3.9 vs. 46.8 ± 8.8, p < 0.01). Perfused capillaries (63.1 ± 17.7 vs. 81.1 ± 20.7, p < 0.001) and the BF index (2.4 ± 0.6 vs. 1.3 ± 0.1, p < 0.001) significantly increased under 7-NI given at the re-flow onset.
Collateral support in the penumbra is initiated during ischemia, and may be increased during early re-flow by neuronal NOS inhibition (given in pre- and post-treatment), which may preserve brain tissue in juvenile rats.
侧支循环的发展被认为是一种内在的代偿机制，用于在缺血后恢复受损的血液灌注，至少在半暗带区域是这样。我们研究了幼鼠大脑缺血再灌注后的动态宏观和微观循环，并评估了神经元型一氧化氮合酶（nNOS）抑制对侧支血流的影响。
对14日龄（P14）大鼠进行缺血再灌注，并分别用磷酸盐缓冲液（PBS）或7-硝基吲唑（7-NI，一种nNOS抑制剂，25mg/kg）进行处理。使用二维彩色编码脉冲超声成像测量动脉血流量（BF）。激光散斑对比（LSC）成像和侧流暗视野视频显微镜分别用于测量皮质和微血管血流量。
在基础状态下，与PBS相比，7-NI使颈内动脉血流量（降低约25%）和皮质血流量（降低约30%）减少。在缺血期间，PBS和7-NI处理后基底干平均血流速度增加，表明侧支支持和通畅性的建立。再灌注时，两种情况下颈内动脉血流量立即恢复到基础值。如LSC成像和侧流暗视野视频显微镜所示，与PBS相比，7-NI组在早期再灌注期间半暗带组织中的侧支血流增加。在缺血前给予7-NI时，与PBS相比，灌注毛细血管的比例显著增加（67.0±3.9对46.8±8.8，p<0.01）。在再灌注开始时给予7-NI时，灌注毛细血管（63.1±17.7对81.1±20.7，p<0.001）和血流指数（2.4±0.6对1.3±0.1，p<0.001）显著增加。
半暗带区域的侧支支持在缺血期间启动，并且在早期再灌注期间可能通过神经元型一氧化氮合酶抑制（预处理和后处理时给予）而增加，这可能保护幼鼠的脑组织。
