Eskandari Ramin, Harris Carolyn A, McAllister James P
Division of Pediatric Neurosurgery, Department of Neurosurgery, University of Utah, 175 North Medical Drive, Salt Lake City, UT 84132, USA.
Childs Nerv Syst. 2011 Dec;27(12):2067-76. doi: 10.1007/s00381-011-1552-4. Epub 2011 Aug 17.
Reactive astrocytosis has been implicated in injury and recovery patterns associated with hydrocephalus. To investigate temporal changes in astrogliosis during the early progression of hydrocephalus, after shunting, and after long-term ventriculomegaly, glial fibrillary protein (GFAP) levels were analyzed in a feline model.
Obstructive hydrocephalus was induced in 10-day-old kittens by intracisternal injections of 25% kaolin. Acute non-shunted animals were killed 15 days post-kaolin injection to represent the pre-shunt condition. Shunt-treated animals received ventriculoperitoneal shunts 15 days post-injection and were killed 10 or 60 days later to represent short- and long-term recovery periods. Chronic untreated animals had Ommaya reservoirs implanted 15 days post-kaolin, which were tapped intermittently until they were killed 60 days later. Ventriculomegaly was monitored by neuroimaging before and after shunting and at death. RNA and total protein from primary visual cortex were analyzed by Northern and Western blotting.
GFAP RNA and protein levels for acute and chronic non-shunted hydrocephalic animals were 77% and 247% (p < 0.01) and 659% (p < 0.05) and 871% (p < 0.05) higher than controls, respectively. Shunted animals with short-term recovery demonstrated a mismatch in GFAP levels, with RNA expression decreasing 26% and protein increasing 335% (p < 0.01). Shunted animals with a long-term recovery exhibited GFAP RNA and protein levels 201% and 357% above normal, respectively.
These results indicate that a reactive astrocytic response continues to rise dramatically in chronic hydrocephalus, suggesting ongoing gliosis and potential damage. Shunting partially ameliorates the continuation of astrogliosis, but does not completely reverse this inflammatory reaction even after a long recovery.
反应性星形细胞增生与脑积水相关的损伤和恢复模式有关。为了研究脑积水早期进展过程中、分流术后以及长期脑室扩大后星形胶质细胞增生的时间变化，在猫模型中分析了胶质纤维酸性蛋白（GFAP）水平。
通过脑池内注射25%高岭土在10日龄小猫中诱导梗阻性脑积水。在注射高岭土15天后处死急性未分流动物以代表分流前状态。分流治疗的动物在注射后15天接受脑室腹腔分流，并在10或60天后处死以代表短期和长期恢复期。慢性未治疗动物在高岭土注射15天后植入Ommaya储液器，间歇性抽取脑脊液直至60天后处死。在分流前后和死亡时通过神经影像学监测脑室扩大情况。通过Northern和Western印迹法分析初级视觉皮层的RNA和总蛋白。
急性和慢性未分流脑积水动物的GFAP RNA和蛋白水平分别比对照组高77%和247%（p<0.01）以及659%（p<0.05）和871%（p<0.05）。短期恢复的分流动物GFAP水平不匹配，RNA表达下降26%，而蛋白增加335%（p<0.01）。长期恢复的分流动物的GFAP RNA和蛋白水平分别比正常水平高201%和357%。
这些结果表明，在慢性脑积水中反应性星形细胞反应持续急剧上升，提示持续的胶质细胞增生和潜在损伤。分流可部分改善星形胶质细胞增生的持续情况，但即使经过长时间恢复也不能完全逆转这种炎症反应。
