Llewellyn-Smith I J, Cassam A K, Krenz N R, Krassioukov A V, Weaver L C
Cardiovascular Medicine and Centre for Neuroscience, Flinders University, South Australia, Australia.
Neuroscience. 1997 Oct;80(4):1225-35. doi: 10.1016/s0306-4522(97)00155-3.
Spinal cord injury destroys bulbospinal amino acid-containing pathways to sympathetic preganglionic neurons and severely disrupts blood pressure control, resulting in resting or postural hypotension and episodic hypertension. Almost all immunoreactivity for the excitatory amino acid L-glutamate has been reported to disappear from autonomic areas of the cord caudal to a transection, apparently depriving autonomic neurons of their major excitatory input. However, the magnitude of the neurogenic episodic hypertension after cord injury suggests that excitatory inputs to sympathetic preganglionic neurons must still be present. Moreover, the hypotension associated with high spinal injuries may reflect a enhanced role for inhibitory transmitters, such as GABA. This apparent contradiction regarding the presence of glutamate and lack of information about GABA prompted the present investigation. In rats seven days after spinal cord transection, we examined identified sympathetic preganglionic neurons caudal to the injury for the presence of synapses or direct contacts from varicosities that were immunoreactive for the amino acids, L-glutamate and GABA. Adrenal sympathetic preganglionic neurons were retrogradely labelled with cholera toxin B subunit and amino acid immunoreactivity was revealed with post-embedding immunogold labelling. In single ultrathin sections, 46% (98/212) of the synapses or direct contacts on adrenal sympathetic preganglionic neurons were immunoreactive for glutamate and 39% (83/214) were immunoreactive for GABA. Analysis of inputs with the physical disector yielded similar results for the two amino acids. The proportions of glutamatergic or GABAergic synapses on cell bodies and dendrites were similar. When alternate ultrathin sections were stained to reveal glutamate or GABA immunoreactivity, either one or the other amino acid occurred in 78.4% (116/148) of inputs; 4.1% (6/148) of inputs contained both amino acids and 17.5% (26/148) of inputs contained neither. These results demonstrate that nerve fibres immunoreactive for the neurotransmitter amino acids, glutamate and GABA, provide most of the input to sympathetic preganglionic neurons caudal to a spinal cord transection. Synapses containing glutamate and GABA could provide the anatomical substrate for the exaggerated sympathetic reflexes and the low sympathetic tone that result from spinal cord injury.
脊髓损伤会破坏通向交感神经节前神经元的含球脊髓氨基酸通路，并严重扰乱血压控制，导致静息性或体位性低血压以及发作性高血压。据报道，几乎所有对兴奋性氨基酸L-谷氨酸的免疫反应性在脊髓横断平面以下的自主神经区域消失，显然使自主神经神经元失去了主要的兴奋性输入。然而，脊髓损伤后神经源性发作性高血压的程度表明，交感神经节前神经元的兴奋性输入必定仍然存在。此外，与高位脊髓损伤相关的低血压可能反映了抑制性递质（如γ-氨基丁酸）的作用增强。关于谷氨酸的存在以及γ-氨基丁酸信息的缺乏这一明显矛盾促使了本研究。在脊髓横断7天后的大鼠中，我们检查了损伤平面以下已鉴定的交感神经节前神经元，以寻找对氨基酸L-谷氨酸和γ-氨基丁酸有免疫反应性突触或来自曲张体的直接接触。肾上腺交感神经节前神经元用霍乱毒素B亚单位进行逆行标记，并用包埋后免疫金标记显示氨基酸免疫反应性。在单个超薄切片中，肾上腺交感神经节前神经元上46%（98/212）的突触或直接接触对谷氨酸有免疫反应性，39%（83/214）对γ-氨基丁酸有免疫反应性。用物理分割器分析输入得到了两种氨基酸的相似结果。细胞体和树突上谷氨酸能或γ-氨基丁酸能突触的比例相似。当交替的超薄切片染色以显示谷氨酸或γ-氨基丁酸免疫反应性时，78.4%（116/148）的输入含有其中一种氨基酸；4.1%（6/148）的输入同时含有两种氨基酸，17.5%（26/148）的输入两种氨基酸都不含有。这些结果表明，对神经递质氨基酸谷氨酸和γ-氨基丁酸有免疫反应性的神经纤维为脊髓横断平面以下的交感神经节前神经元提供了大部分输入。含有谷氨酸和γ-氨基丁酸的突触可为脊髓损伤导致的过度交感反射和低交感神经张力提供解剖学基础。
