Department of Neurology, Maastricht University Medical Center, Oxfordlaan 10, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Neurobiol Dis. 2011 Sep;43(3):625-34. doi: 10.1016/j.nbd.2011.05.011. Epub 2011 May 23.
Vascular cognitive impairment has been related to dysfunction of the central cholinergic system. Studies exploring the putative relationship between vascular cognitive impairment and cholinergic dysfunction have largely been aimed at symptomatic cholinergic treatment rather than focusing on etiological and pathological factors. The present study characterizes chronic responses of the cholinergic system to focal cerebral infarction. Two separate experiments investigated changes in receptor responsiveness versus changes in cell number after photothrombotic infarction of the frontal cortex in rat brain. First, we conducted pharmacological magnetic resonance imaging (phMRI) together with pilocarpine injection to assess relative cerebral blood volume (CBV) responses related to cholinergic muscarinic receptor activation. PhMRI was conducted at 1 and 3 weeks after photothrombotic infarction of either the left or right frontal cortex. Second, stereological assessment was performed on choline acetyltransferase (ChAT)-immunostained sections to determine cholinergic cell body count in several basal forebrain nuclei at 4 weeks after infarction. Significant reductions in relative CBV responses were observed both inside the ischemic area at 1 and 3 weeks, and in areas distant from the lesion at 3 weeks after right-sided frontal cortical infarction. In contrast, cholinergic cell number remained unchanged. These results demonstrate that cholinergic receptor responsiveness may be significantly altered following cerebral infarction, while projecting cholinergic cells are preserved.
血管性认知障碍与中枢胆碱能系统功能障碍有关。探索血管性认知障碍与胆碱能功能障碍之间潜在关系的研究主要集中在对症胆碱能治疗上，而不是关注病因和病理因素。本研究描述了局灶性脑梗死对胆碱能系统的慢性反应。两项独立的实验研究了光血栓性大脑皮质梗死大鼠大脑中受体反应性与细胞数量变化之间的关系。首先，我们进行了药理学磁共振成像（phMRI）和毛果芸香碱注射，以评估与胆碱能毒蕈碱受体激活相关的相对脑血容量（CBV）反应。phMRI 在光血栓性左或右大脑皮质梗死 1 周和 3 周后进行。其次，在梗死 4 周后，对胆碱乙酰转移酶（ChAT）免疫染色切片进行立体学评估，以确定几个基底前脑核中的胆碱能细胞体计数。在梗死 1 周和 3 周时，在缺血区域内以及在右侧大脑皮质梗死 3 周时，远离病变区域内，均观察到相对 CBV 反应明显降低。相比之下，胆碱能细胞数量保持不变。这些结果表明，脑梗死后胆碱能受体反应性可能发生显著改变，而投射胆碱能细胞则保持不变。
