水腦對海馬迴之影響：以高嶺土誘發大鼠之模式

Abstract

水腦被發現會影響個體的學習能力，而目前普遍相信大腦中的海馬迴與學習及記憶有著密切的關係，因此為了探討水腦降低動物學習能力的形態學基礎，我們以高嶺土（kaolin）誘發大鼠阻塞型水腦症，探討手術後一週（急性期）和四週（慢性期）海馬迴形態學上的變化。結果顯示：大鼠顱內壓在手術後一週明顯上升，而且維持至慢性期，而腦室則隨存活週數逐漸擴大。分析個別動物同時測得的顱內壓與腦室面積估算，發現隨著腦壓增加，腦室也隨著擴張。另外，腦室擴張愈大，大腦皮質層變得愈薄，其中白質之變化尤為明顯。動物的體重增加速率也因水腦的發生而比正常組慢。巨觀下，整個海馬迴承受特別明顯的橫向擠壓。免疫組織染色顯示，不論是急性期或慢性期，海馬迴中CA1、CA3區的小膠細胞與星形神經膠細胞的數目皆增加，而表現豐富一氧化氮合成酶的細胞數目在CA區則無明顯變化。當我們以細胞內染料注射法探討海馬迴CA3區錐狀神經元整體樹突叢時發現樹突總長度在急性期時即明顯變短，這些變化集中在頂樹突；細胞所有樹突表面樹突棘的密度在急性期與慢性期都明顯降低。 綜上所述，我們目前的結果顯示阻塞型水腦壓迫除導致海馬迴發生普遍性的神經膠細胞反應外還造成其主要神經元—錐狀神經細胞的樹突叢變短且樹突棘密度降低。這些型態上的變化意味著水腦影響了海馬迴接受訊息的功能，由於錐狀神經細胞元也是海馬迴的傳出神經元，因此這些變化也改變了海馬迴的功能，這些型態學上的變化可能是水腦降低動物學習能力的基礎。

Hydrocephalus is known to affect learning, which is generally believed to be an important function of the hippocampus. To investigate the anatomic substrate of this hydrocephalus-induced deficiency, we took advantage of a kaolin-induced rat obstructive hydrocephalus model and studied its effect on hippocampus. Hippocampus was studied 1 (acute) and 4 week (chronic) following kaolin injection into cisterna magna. The intracranial pressure of animals increased significantly in acute, and persisted to chronic cases. Intracranial pressure increased as the ventricules gained in sizes. Thinning of white matter was more dramatic than gray matter as the ventriculomegaly advanced. Hippocampus appeared to be compressed more obviously in the horizontal direction based on the alteration of its shape. In both CA3 and CA1 areas, microglial and astrocytic reactions was inducted in both acute and chronic animals. The density of NOS-immunoreactive neurons in hippocampus remained low following hydrocephalus. As to the dendritic arbors of the CA3 pyramidal neurons, intracellular dye injection revealed that the total dendritic length, which was caused by a specific decrease of apical dendrites, of acute animals was significantly decreased. The density of dendritic spines on all the dendrites of this neuron both acute and chronic animals was significantly decreased. In conclusion, in addition to reactive glial responses, obstructive hydrocephalus caused the remodeling of the dendritic arbors of CA3 pyramidal neurons. The alteration of receiving structures implies changes of hippocampal input as well as output. The phenomena we observed are likely to underlie the impairment of learning reported of hydrocephalic animals.