Schmidt R H, Kasik S A, Bhatnagar R K
Brain Res. 1980 Jun 2;191(1):173-90. doi: 10.1016/0006-8993(80)90321-2.
Rat pups were injected intracisternally with 20, 40 or 80 microgram of 6-hydroxydopamine (6-OHDA) at various ages over the first 12 postnatal days in order to determine the critical period of the noradrenergic regenerative-sprouting response in the cerebellum. Twenty-four hours after the treatment NE fibers in the cerebellum had become extensively degenerated. NE levels were reduced by greater than 90-95% and histofluorescence microscopy revealed an absence of innervation except for lesioned axon stumps in the basal white matter and peduncles. The 80 microgram dose produced considerable cellular degeneration in the locus coeruleus and no regenerative growth was seen to follow this treatment. Following the two lower doses, however, regenerative growth did occur. This was maximal in those rats treated closest to birth and declined progressively to become insignificant in rats which were treated on postnatal days 5-12, depending upon the cerebellar subregion. This decline in regenerative potential paralleled the time course for development of NE levels in control cerebella. For this reason the mechanism(s) controlling noradrenergic developmental and regenerative growth in the cerebellum appear to be similar. Such regenerative growth may thus be a useful model for the study of developmental growth of locus coeruleus axons. Contrary to the cerebellar projection, regenerative growth of the forebrain noradrenergic projection was not detected until the rats were between 7 and 12 days old at the time of treatment. This regeneration in the cerebral cortex was preceded by incomplete initial destruction of NE fibers there, in apparent similarity to regenerative growth described to occur in the adult rat forebrain.
在出生后的头12天内，于不同年龄给新生大鼠脑池内注射20、40或80微克的6-羟基多巴胺（6-OHDA），以确定小脑去甲肾上腺素能再生芽生反应的关键期。治疗后24小时，小脑中的去甲肾上腺素（NE）纤维已广泛变性。NE水平降低了90%-95%以上，组织荧光显微镜检查显示除了基底白质和脚中的受损轴突残端外，没有神经支配。80微克剂量在蓝斑产生了相当程度的细胞变性，且此剂量处理后未见再生生长。然而，给予两个较低剂量后，确实发生了再生生长。在最接近出生时接受治疗的大鼠中，这种再生生长最为明显，并逐渐下降，在出生后第5-12天接受治疗的大鼠中，根据小脑亚区的不同，再生生长变得不明显。这种再生潜能的下降与对照小脑中NE水平的发育时间进程平行。因此，控制小脑中去甲肾上腺素能发育和再生生长的机制似乎相似。这样的再生生长可能是研究蓝斑轴突发育生长的一个有用模型。与小脑投射相反，直到治疗时大鼠在7至12日龄之间，才检测到前脑去甲肾上腺素能投射的再生生长。大脑皮质中的这种再生之前，该部位的NE纤维有不完全的初始破坏，这明显类似于成年大鼠前脑中描述的再生生长。
