Department of Medical Biology, Medical Faculty, Erciyes University, 38030 Kayseri, Turkey.
Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38030 Kayseri, Turkey.
Int J Mol Sci. 2022 Dec 10;23(24):15699. doi: 10.3390/ijms232415699.
Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic-pituitary-adrenal (HPA) axis either by primary injury to the hypothalamic-hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic-pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (, , , , and ) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.
创伤性脑损伤（TBI）是一个全球性的重大健康问题，影响了数百万人，并导致死亡或永久性损伤。TBI 通过对下丘脑-垂体区域的原发性损伤或通过继发性血管损伤、脑和/或垂体水肿、血管痉挛和炎症来影响下丘脑-垂体-肾上腺（HPA）轴。TBI 后的神经内分泌功能障碍已在所有下丘脑-垂体轴中得到临床描述。我们通过使用皮质控制冲击（CCI）模型在大鼠中建立了轻度 TBI（mTBI）。在 TBI 后急性（24 小时）和慢性（30 天）组中收集下丘脑、垂体和肾上腺，并研究了与自噬（、、、和）和凋亡（原半胱天冬酶-3、裂解半胱天冬酶-3）相关的转录本和蛋白。TBI 后，下丘脑、垂体和肾上腺中的自噬相关转录本减少，但这并未反映在自噬相关蛋白水平上。相反，在急性期肾上腺和慢性期垂体中，与凋亡相关的蛋白标志物增加。TBI 应激诱导 HPA 轴中自噬相关转录本的变化，而不改变其蛋白水平。相比之下，在急性期肾上腺和慢性期垂体中，与凋亡相关的蛋白标志物增加。这可能导致通过下丘脑、垂体和肾上腺的通讯受损。这可能解释了慢性期中凋亡和炎症增加导致的永久性垂体损伤。这些结果有助于阐明 TBI 后发生的内分泌功能障碍（如垂体和肾上腺功能不全）的机制。尽管肾上腺未直接受到 TBI 的影响，但我们建议在 TBI 后急性期不应忽视肾上腺与下丘脑和垂体的作用。
