Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury.
Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury.
复制标题
横向液体冲击损伤后海马 CA3 对低水平红藻氨酸的脆弱性增加。
DOI：
10.1089/089771503765355496
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发表时间：
2003
影响因子：
4.2
通讯作者：
Hovda,DavidA
中科院分区：
文献类型：
--
作者：
Zanier,ElisaRoncati;Lee,StefanM;Vespa,PaulM;Giza,ChristopherC;Hovda,DavidA
本研究旨在确定低剂量的谷氨酸类似物海人酸（KA）诱导的神经元活动的继发性增加是否加剧了海马区的解剖损伤 轻微的侧向液压冲击脑损伤在LFP损伤的大鼠（n= 16）中，在创伤后1h腹腔内注射KA（9 mg/kg）。CA 3、CA 4和肺门神经元丢失 通过二维细胞计数对7天时的区域进行定量。通过测量局部葡萄糖代谢率（lCMRglc）评估KA注射后15分钟的海马激活。以下 LFP + KA组同侧CA 3、CA 4和肺门神经元的数量分别比未处理大鼠（n= 3）减少62.7%、75.7%和52.1%。这些CA 3和CA 4神经元计数 与LFP +生理盐水组（n= 5）和假手术+ KA组（n= 9）相比也显著降低。用于评定行为性癫痫发作严重程度的中位Racine评分在LFP + KA中为4分 假手术+ KA组为2例（p< 0.015），提示损伤后癫痫发作阈值降低。LFP + KA后CA 3的lCMRglc为121.8 ± 2.0（平均值± SE）， 71.5对侧± 5.4（p< 0.0012）。在CA 3，CA 4和门区的[14 C]氨基异丁酸测量的血脑屏障通透性没有发现变化。我们的结论是 LFP后1 h低水平KA的存在显著增加海马激活的程度，并诱导同侧CA 3和CA 4锥体神经元的显著损失。神经元兴奋 细胞脆弱性的时间可以触发或放大功能受损但可能存活的组织中的继发性损伤的循环。
This study was designed to determine whether a secondary increase in neuronal activity induced by a low dose of kainic acid (KA), a glutamate analogue, exacerbates the anatomical damage in hippocampal regions following a mild lateral fluid percussion (LFP) brain injury. KA (9 mg/kg) was injected intraperitoneally in LFP-injured rats (n= 16) 1 h post-trauma. The neuronal loss in the CA3, CA4, and hilar regions at 7 days was quantified by two-dimensional cell counts. Hippocampal activation 15 min following KA injection was assessed by measuring local glucose metabolic rates (lCMRglc). Following LFP + KA, the ipsilateral side exhibited a 62.7%, 75.7%, and 52.1% decrease in the number of CA3, CA4 and hilar neurons, respectively, compared to naive rats (n= 3). These CA3 and CA4 neuronal counts were also significantly decreased compared to LFP + saline (n= 5) and sham + KA (n= 9) groups. The median Racine Score, used to rate the severity of behavioral seizures, was 4 in LFP + KA and 2 in sham + KA groups (p< 0.015), suggesting a reduction in seizure threshold following injury. lCMRglc in CA3 following LFP + KA was 121.8 ± 2.0 (mean ± SE) ipsilaterally and 71.5 ± 5.4 contralaterally (p< 0.0012). No changes were found in the BBB permeability as measured by [14C]aminoisobutyric acid in CA3, CA4, and hilar regions. We conclude that the presence of low-level KA 1 h after LFP dramatically increases the extent of hippocampal activation and induces a striking loss of ipsilateral CA3 and CA4 pyramidal neurons. Neuronal excitation during a time of cellular vulnerability may trigger or amplify the cycle of secondary damage in functionally impaired, but potentially viable, tissue.