Nozaki K, Boccalini P, Moskowitz M A
Stroke Research Laboratory, Neurosurgery and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Neuroscience. 1992 Aug;49(3):669-80. doi: 10.1016/0306-4522(92)90235-t.
The expression of c-fos protein was examined by immunohistochemistry in serial sections of brainstem following the instillation of either autologous arterial blood (0.3 ml) or mock cerebrospinal fluid (0.3 ml) through a catheter placed in the cisterna magna, or following catheter placement alone in pentobarbital-anesthetized Sprague-Dawley rats. After injection, blood was distributed within the subarachnoid space surrounding the brainstem and in the region of the circle of Willis. c-fos protein-like immunoreactivity was present at 1 h, peaked at 2 h and decreased by 8 h. At 2 h, immunoreactivity was strongly expressed within trigeminal nucleus caudalis (lamina I, IIo), as well as within nucleus of the solitary tract, area postrema, ependyma, pia mater and arachnoid in every animal. Moderate labeling was found in parabrachial nucleus, medullary lateral reticular nucleus and central gray. Sparse labeling was present in trigeminal nucleus caudalis (lamina III-V) and trigeminal nucleus interpolaris; few or no labeled cells were detected in other parts of the trigeminal nuclear complex, thalamus, cerebral cortex, cerebellar cortex or trigeminal ganglion. The number of positive cells was not related to the volume of injectate but was related to the amount of injected blood. The density of cell labeling evoked by injecting mock cerebrospinal fluid or after catheter placement was markedly lower than after blood in all brainstem areas. The number of labeled cells was greatly reduced within trigeminal nuclear complex, parabrachial nucleus and medullary lateral reticular nucleus, but not within the nucleus of the solitary tract, area postrema or ependyma when blood was injected into adult animals in which unmyelinated C-fibers were destroyed by neonatal capsaicin treatment. Similar results were obtained after blood was instilled into the cisterna magna of rats in which meningeal afferents were chronically sectioned at the ethmoidal foramen bilaterally. We conclude that blood in the subarachnoid space is an effective stimulus for activating c-fos expression within subpopulations of brainstem neurons. Activation within trigeminal nucleus caudalis is mediated in large part by excitation of small-caliber meningeal afferents (trigeminovascular fibers), whereas c-fos expression within nucleus of the solitary tract and area postrema may reflect direct stimulation of blood or blood products, or possibly the response to autonomic activation from noxious stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
通过免疫组织化学方法，在戊巴比妥麻醉的Sprague-Dawley大鼠中，经置于大池的导管注入自体动脉血（0.3 ml）或模拟脑脊液（0.3 ml），或仅放置导管后，检测脑干连续切片中c-fos蛋白的表达。注射后，血液分布于脑干周围的蛛网膜下腔以及 Willis 环区域。c-fos蛋白样免疫反应在1小时出现，2小时达到峰值，8小时下降。在2小时时，每只动物的三叉神经尾侧核（I层、IIo层）、孤束核、最后区、室管膜、软脑膜和蛛网膜内均强烈表达免疫反应。臂旁核、延髓外侧网状核和中央灰质有中度标记。三叉神经尾侧核（III-V层）和三叉神经极间核有稀疏标记；在三叉神经核复合体、丘脑、大脑皮层、小脑皮层或三叉神经节的其他部位，未检测到或仅检测到少量标记细胞。阳性细胞数量与注射量无关，但与注入的血量有关。在所有脑干区域，注射模拟脑脊液或放置导管后引起的细胞标记密度明显低于注射血液后。当向新生辣椒素处理破坏了无髓鞘C纤维的成年动物注入血液时，三叉神经核复合体、臂旁核和延髓外侧网状核内的标记细胞数量大大减少，但孤束核、最后区或室管膜内的标记细胞数量未减少。在双侧筛孔处慢性切断脑膜传入神经的大鼠大池注入血液后，也得到了类似结果。我们得出结论，蛛网膜下腔中的血液是激活脑干神经元亚群内c-fos表达的有效刺激物。三叉神经尾侧核内的激活在很大程度上是由小口径脑膜传入神经（三叉神经血管纤维）的兴奋介导的，而孤束核和最后区内的c-fos表达可能反映了血液或血液成分的直接刺激，或者可能是对有害刺激引起的自主激活的反应。（摘要截于400字）
