The effects of repeat traumatic brain injury on the pituitary in adolescent rats

Abstract

Adolescents are one of the highest groups at risk for sustaining both traumatic brain injury (TBI) and repeat TBI (RTBI). Consequences of endocrine dysfunction following TBI have been routinely explored in adults, but studies in adolescents are limited, and show an incidence rate of endocrine dysfunction in 16-61% in patients, 1-5 years after injury. Similar to in adults, the most commonly affected axis is growth hormone (GH) and insulin-like growth hormone 1 (IGF-1). Despite TBI being the primary cause of morbidity and mortality among the pediatric population, there are currently no experimental studies specifically addressing the occurrence of pituitary dysfunction in adolescents. The present study investigated whether a sham, single injury or four repeat injuries (24 h interval) delivered to adolescent rats resulted in disruption of the GH/IGF-1 axis. Circulating levels of basal GH and IGF-1 were measured at baseline, 24 h, 72 h, 1 week, and 1 month after injury, and vascular permeability of the pituitary gland was quantified via Evans Blue dye extravasation. Changes in weight and length of animals were measured as a potential consequence of GH and IGF-1 disruption. The results from the current study demonstrate that RTBI results in significant acute and chronic decreases in circulation of GH and IGF-1, reduction in weight gain and growth, and an increase in Evans Blue dye extravasation in the pituitary compared with sham and single injury animals. RTBI causes significant disruption of the GH/IGF-1 axis that may ultimately affect normal cognitive and physical development during adolescence.

FIG. 1.

Location and diagram of the pituitary gland. The pituitary is located in the third ventricle in the sella turcica and is connected to the hypothalamus via the infundibular stalk. Area inside circle shows portal vessels and axons from the hypothalamus enter the pituitary through the infundibular stalk. Forces sustained during traumatic brain injury (TBI) causes ischemia as a result of compression from swelling within the sella turcica and shearing of vessels and axons leading to loss of input from the hypothalamus.

FIG. 2.

Changes in the growth hormone/insulin-like growth hormone 1 (GH/IGF-1) axis after injury. (A) Average (±SEM) changes in circulating GH at baseline and at 24 h, 72 h, 1 week, and 1 month after single or repeat injury. *p<0.05 (B) Average (±SEM) changes in circulating IGF-1 at baseline and at 24 h, 72 h, 1 week, and 1 month after single or repeat injury. *p<0.05

FIG. 3.

Repeat traumatic brain injury (RTBI) induced increase in Evans Blue dye extravasation in the pituitary gland. Graph show the average (±SEM) change in Evans Blue dye permeability in the pituitary gland 24 h after sham, single, or repeat injury. *p<0.05