Traumatic brain injury (TBI) can damage the hypothalamus and cause improper activation of the growth hormone (GH) axis, leading to growth hormone deficiency (GHD). GHD is one of the most prevalent endocrinopathies following TBI in adults; however, the extent to which GHD affects juveniles remains understudied. We used postnatal day 17 rats (n = 83), which model the late infantile/toddler period, and assessed body weights, GH levels, and number of hypothalamic somatostatin neurons at acute (1, 7 days post injury (DPI)) and chronic (18, 25, 43 DPI) time points. We hypothesized that diffuse TBI would alter circulating GH levels because of damage to the hypothalamus, specifically somatostatin neurons. Data were analyzed with generalized linear and mixed effects models with fixed effects interactions between the injury and time. Despite similar growth rates over time with age, TBI rats weighed less than shams at 18 DPI (postnatal day 35; P = 0.03, standardized effect size [d] = 1.24), which is around the onset of puberty. Compared to shams, GH levels were lower in the TBI group during the acute period (P = 0.196; d = 12.3) but higher in the TBI group during the chronic period (P = 0.10; d = 52.1). Although not statistically significant, TBI-induced differences in GH had large standardized effect sizes, indicating biological significance. The mean number of hypothalamic somatostatin neurons (an inhibitor of GH) positively predicted GH levels in the hypothalamus but did not predict GH levels in the somatosensory cortex. Understanding TBI-induced alterations in the GH axis may identify therapeutic targets to improve the quality of life of pediatric survivors of TBI.

创伤性脑损伤 (TBI) 会损害下丘脑并导致生长激素 (GH) 轴激活不当，从而导致生长激素缺乏 (GHD)。GHD 是成人 TBI 后最常见的内分泌疾病之一；然而，GHD 对青少年的影响程度仍未得到充分研究。我们使用出生后第 17 天的大鼠（n = 83）作为婴儿/幼儿晚期的模型，并评估了急性损伤（损伤后 1、7 天 (DPI)）和慢性损伤时的体重、GH 水平和下丘脑生长抑素神经元的数量。 （18、25、43 DPI）时间点。我们假设弥漫性 TBI 会因为下丘脑（特别是生长抑素神经元）受损而改变循环 GH 水平。使用广义线性和混合效应模型对数据进行分析，其中损伤和时间之间存在固定效应相互作用。尽管随着年龄的增长，TBI 大鼠的生长速度相似，但在 18 DPI（出生后第 35 天；P = 0.03，标准化效应大小 [ d ] = 1.24）时，即青春期开始前后，TBI 大鼠的体重低于假大鼠。与假手术组相比，急性期 TBI 组的 GH 水平较低（P = 0.196；d  = 12.3），但慢性期 TBI 组的 GH 水平较高（P = 0.10；d  = 52.1）。尽管在统计学上不显着，但 TBI 引起的 GH 差异具有较大的标准化效应值，表明具有生物学意义。下丘脑生长抑素神经元（GH 抑制剂）的平均数量可正向预测下丘脑中的 GH 水平，但不能预测体感皮层中的 GH 水平。了解 TBI 引起的 GH 轴改变可以确定治疗靶点，以改善 TBI 儿科幸存者的生活质量。