Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology following Blast Exposure.
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)-1β, 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-1β, 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.
1 School of Biomedical Engineering and Sciences, Virginia Tech , Blacksburg, Virginia.
Pamela J
PJ
VandeVord
1 School of Biomedical Engineering and Sciences, Virginia Tech , Blacksburg, Virginia.
Venkata Siva Sai Sujith
VS
Sajja
1 School of Biomedical Engineering and Sciences, Virginia Tech , Blacksburg, Virginia.
Evon
E
Ereifej
1 School of Biomedical Engineering and Sciences, Virginia Tech , Blacksburg, Virginia.
Amy
A
Hermundstad
1 School of Biomedical Engineering and Sciences, Virginia Tech , Blacksburg, Virginia.
Shijie
S
Mao
2 Research Services, John D. Dingell VA Medical Center , Detroit, Michigan.
Timothy J
TJ
Hadden
D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001753:Blast Injuries / Q000150:complications*; D001835:Body Weight; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D004700:Endocrine System Diseases / Q000209:etiology / Q000378:metabolism*; D007027:Hypothalamic Diseases / Q000209:etiology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D052242:Adiponectin; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D020738:Leptin; D000324:Adrenocorticotropic Hormone
+6 adipose tissue; ACTH; adiponectin; blast; hypothalamus; leptin