Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells After Focal Cerebral Ischemia in Spontaneously Hypertensive Rats.
Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells After Focal Cerebral Ischemia in Spontaneously Hypertensive Rats.
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DOI：
10.3727/096368916x690557
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发表时间：
2016
影响因子：
3.3
通讯作者：
Arai K
中科院分区：
文献类型：
--
作者：
Liang AC;Mandeville ET;Maki T;Shindo A;Som AT;Egawa N;Itoh K;Chuang TT;McNeish JD;Holder JC;Lok J;Lo EH;Arai K
衰老和血管合并症（如高血压）是影响大脑如何应对中风的关键辅助因素。缺血应激诱导年轻脑中的神经发生和少突胶质细胞生成。然而，目前尚不清楚这些代偿机制是否可以维持，即使在病理性高血压和老年状态。为了阐明高血压条件下卒中后与年龄相关的重塑能力，我们评估了3个月龄和12个月龄自发性高血压大鼠（SHR）短暂局灶性脑缺血后急性和亚急性期的梗死体积、行为结局以及神经发生和少突神经发生的替代标记物。苏木精-伊红染色显示，3和12月龄SHR在局灶性脑缺血后3和14天表现出相似的梗死体积。然而，与3个月大的SHR相比，12个月大的SHR的行为缺陷（神经评分评估和粘合剂去除试验）的恢复明显较少。与此同时，在第3天，12个月大的SHR的梗死边缘区或室下区附近的nestin阳性神经干/祖细胞（NSPCs）的数量低于3个月大的SHR。同样，在第3天，12个月大的SHR胼胝体中PDGF-R-α阳性少突胶质前体细胞（OPC）的数量较低。较低水平的NSPC和OPC数量伴随着较低的CREB磷酸化表达水平。到缺血后第14天，12月龄SHR的NSPC和OPC数量恢复到与3月龄SHR相似的水平。但是，即使在第14天，增殖的NSPCs（Ki 67 +nestin+细胞）和增殖的OPCs（Ki 67 +PDGF-R-α+细胞）的数量在老年大脑中仍然较低。总之，这些发现表明，即使在高血压条件下，衰老也可能降低脑卒中后神经发生和少突神经发生的代偿反应。
Aging and vascular comorbidities such as hypertension comprise critical co-factors that influence how the brain responds to stroke. Ischemic stress induces neurogenesis and oligodendrogenesis in younger brains. However, it remains unclear whether these compensatory mechanisms can be maintained even under pathologic hypertensive and aged states. To clarify the age-related remodeling capacity after stroke under hypertensive conditions, we assessed infarct volume, behavioral outcomes, and surrogate markers of neurogenesis and oligodendrogenesis in acute and sub-acute phases after transient focal cerebral ischemia in 3 month old and 12 month old spontaneously hypertensive rats (SHRs). Hematoxylin and eosin staining showed that 3 and 12 month old SHRs exhibited similar infarction volumes at both 3 and 14 days after focal cerebral ischemia. However, recovery of behavioral deficits (neurological score assessment and adhesive removal test) were significantly less in 12-month-old SHRs compared to 3-month-old SHRs. Concomitantly, numbers of nestin-positive neural stem/progenitor cells (NSPCs) near the infarct border area or subventricular zone in 12-moth-old SHRs were lower than 3-month-old SHRs at day 3. Similarly, numbers of PDGF-R-α-positive oligodendrocyte precursor cells (OPCs) in corpus callosum was lower in 12-month-old SHRs at day 3. Lower levels of NSPC and OPC numbers were accompanied by lower expression levels of CREB phosphorylation. By day 14 post-ischemia, NSPC and OPC numbers in 12-month-old SHRs recovered to similar levels as in 3-month-old SHRs. But the numbers of proliferating NSPCs (Ki67+nestin+ cells) and proliferating OPCs (Ki67+PDGF-R-α+ cells) remained lower in the older brains even at day 14. Taken together, these findings suggest that aging may also decrease post-stroke compensatory responses for neurogenesis and oligodendrogenesis even under hypertensive conditions.