Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury

Abstract

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.

Thyrotropic Axis and Disorders of Consciousness in Acquired Brain Injury: A Potential Intriguing Association?

“…Although serum TSH levels are usually normal during the post-acute phase of ABI, we were unable to find a correlation between TSH and THs, suggesting a central derangement of pituitary TSH secretion ( 33 ). It is known that thyrotropic axis signaling in the brain can be disrupted by a severe damage ( 34 ), likely through mechanisms that involved both THs signaling deregulation and alterations in TRH and TSH secretion and feedbacks ( 32 , 35 ). Like other peripheral tissues, the SNC contains deiodinases, a group of enzymes that is capable of modifying the biologic activity of THs either by activating T4 (type II deiodinase, D2) or by inactivating T4 and T3 (type III deiodinase, D3), thus modulating T3 levels inside the target cells ( 32 ).…”

Metabolic disorders on cognitive dysfunction after traumatic brain injury

“…Notably, the incidence of hypothalamic-pituitary dysfunction is high after TBI. The hypothalamic-pituitary axis plays an important role in neuroendocrine function and the hypothalamic arcuate nucleus (ARC) is central to the peripheral regulation of glucose and lipid metabolism [9,10]. Hypothalamic-pituitary dysfunction affects cognitive function, especially attention, memory, and execution after TBI [11].…”

“…The ARC of the hypothalamus contains two types of neurons that regulate metabolism; namely, neuropeptide Y/agouti-related peptide neurons and pro-opiomelanocortin neurons, which can regulate glucose and lipid metabolism, respectively [9]. After brain injury, the BBB's function is destroyed and inflammatory infiltration occurs, resulting in neuronal injury in the hypothalamic region, which in turn causes a series of neurometabolic dysfunctions [10]. In addition, nonneuronal cells (e.g., microglia, astrocytes) can affect abnormal neuronal cell metabolism through a series of pathways, such as the inflammatory response, oxidative stress, and mitochondrial pathway [26].…”

Molecular and Genetic Immune Biomarkers of Primary and Immune-Therapy Induced Hypophysitis: From Laboratories to the Clinical Practice

“…The clinical relevance of APAs has been keenly discussed in previous research and APAs were widely considered a pathogenic marker of hypophysitis rather than a diagnostic tool. In fact, APAs were reported in other autoimmune disorders of the pituitary gland or in autoimmune systemic diseases, such as Sheehan’s syndrome, idiopathic growth hormone (GH) deficiency, idiopathic hyperprolactinemia, idiopathic hypopituitarism, brain traumatic injury, autoimmune polyendocrine syndromes and empty sella syndrome, but also in patients with pituitary adenomas or in healthy individuals [ 14 , 16 , 17 ]. The experimental hypophysitis of SJL/J models showed that APAs may be detected with a higher concentration in the initial days after mouse immunization and gradually reduce thereafter [ 11 ].…”

“…The experimental hypophysitis of SJL/J models showed that APAs may be detected with a higher concentration in the initial days after mouse immunization and gradually reduce thereafter [ 11 ]. For these reasons, the APAs were also considered clinically helpful for the diagnosis of acute hypophysitis in humans, but only if detected at a high concentration [ 16 ]. Recently, we proved that APAs are more prevalent in patients affected by PAH (68.4%) than in patients affected by not-secreting pituitary adenomas (22%) and in health controls (14%) [ 18 ].…”