Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology following Blast Exposure

Abstract

Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects. An established rodent model of blast neurotrauma was used to induce mild blast-induced neurotrauma. Adipose tissue, blood, and brain samples were collected at one and three months following a single blast exposure. Adipose tissue and blood were evaluated for changes in ACTH, adiponectin, C-reactive protein, glial fibrillary acidic protein, interleukin (IL)-1b, and leptin. The hypothalamus was evaluated for injury using immunohistochemical techniques. The results demonstrated that the weight of the blast animals was significantly less, compared with the sham group. The slower rate of increase in their weight was associated with changes in ACTH, IL-1b, and leptin levels. Further, histological analysis indicated elevated levels of cleaved caspase-3 positive cells within the hypothalamus. The data suggest that long-term outcomes of brain injury occurring from blast exposure include dysfunction of the hypothalamus, which leads to compromised hormonal function, elevated biological stress-related hormones, and subsequent adipose tissue remodeling.

Enduring deficits in memory and neuronal pathology after blast-induced traumatic brain injury

“…Numerous pathological outcomes have been identified in relation to BINT. Neurochemical alterations/imbalance, oxidative stress, mitochondrial dysfunction and BBB disruption have been identified to be important pathological events that are involved at acute stages following BINT 3 4 5 6 7 8 9 10 11 12 13 14 15 21 22 23 . However, the long-term effects on various pathological markers and associated cognitive deficits are currently unclear.…”

“…The majority of reports have shown loss of neuronal populations, while also showing an increase in astrogliosis 3 4 5 6 7 8 9 10 11 12 . The limited number of magnetic resonance imaging studies combined with histopathological data have shown the vulnerability of oligodendrocytes and endothelial cells following BINT 13 14 15 . In conjunction with molecular changes, behavioral abnormalities such as memory impairment and anxiety have been widely demonstrated in acute pre-clinical studies 11 16 17 .…”

“Operator syndrome”: A unique constellation of medical and behavioral health-care needs of military special operation forces

“…TBI has a powerful dysregulating effect on the endocrine system 19 and particularly TBI secondary to blast-wave exposure. 20 It is believed that overactivity of the "hypothalamic-pituitary-adrenal" axis, through acute or chronic stress, disrupts the hormonal interaction (including gonadal and thyroid axes) between this region of the brain and the adrenal gland. This increases the secretion of cortisol and norepinephrine, leading to insomnia or sleep disruption.…”

Diffuse traumatic brain injury affects chronic corticosterone function in the rat

“…As such, TBI survivors can present with deficiencies in one or more hormones, including corticotropins, growth hormones, thyrotropins, and gonadotropins ( 20 ). The variation of hormones disrupted could be based on the type (blast, diffuse, penetrating), mechanics (direction/force of impact) or dynamics (single, repetitive) of the injury, as well as pre-existing conditions (genetic predisposition) ( 23 , 24 , 25 , 26 , 27 , 28 ). Recent longitudinal studies support the idea that a severe injury is more likely to result in chronic endocrine dysfunction, as opposed to a mild injury; however, endocrine dysfunction manifests across the brain injury severity spectrum ( 15 ).…”