This review summarizes the present advance of effects of stress on hippocampal structure and function and the role of hippocampus in feedback regulation of thalamic-pituitary-adrenocortical (HPA) axis during stress. It shows that stress can affect hippocampal structure and function, on the other hand, the hippocampus can also suppress the stress reaction through the feedback regulation of HPA axis, but chronic stress can attenuate this regulation, then significantly impair its structure and function.
Animals ; Hippocampus/physiopathology* ; Humans ; Hypothalamo-Hypophyseal System/physiology* ; Pituitary-Adrenal System/physiology* ; Stress, Physiological/physiopathology*

Traumatic brain injury (TBI) remains a complicated and urgent disease in our modernized cities. It becomes now a public health disease. We have got more and more patients in Neurosurgery Intensive Care Unit following motor vehicle accidents and others causes. TBI brings multiple disorders, from the primary injury to secondary injury. The body received the disturbances in the brain, in the hypothalamo-pituitary-adrenocortical (HPA) axis, in the gastric mucosa, in the immune and neuroendocrine systems. The mortality of TBI is more than 50 000 deaths / year, the third of the mortality of all injuries. Cushing ulcer is one of the severe complications of TBI and its mortality rate is more than 50%. Many studies have improved the management of TBI and the associated complications to give patients a better outcome. Furthers studies need to be done based on the similar methodology to clarify the different steps of the HPA axis and the neuroendocrine change associated. The aim of the present review is to assess the clinical and endocrinal features of hypopituitarism and stress ulcer following TBI.
Brain Injuries ; complications ; physiopathology ; Humans ; Hypopituitarism ; etiology ; Hypothalamo-Hypophyseal System ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Stomach Ulcer ; etiology

BACKGROUNDTraumatic brain injury (TBI) is a heterogeneous condition that can lead to critical LLLness-related corticosteroid insufficiency (CIRCI) causing a high mortality and morbidity. Glucocorticoids were widely used in the clinical management of TBI, but their benefit has been challenged in some studies and their efficacy, especially for treating CIRCI in TBI patients, remains unclear.

METHODSWe conducted a meta-analysis of published data to determine if the controversy is related to clinical dosing and timing of glucocorticoids (GCs) application. We analyzed published reports in four databases (MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and CBMdisc). The published data were stratified into not only low- and high-dose GCs group but also short- and long-term GCs group to compare their effectiveness in improving TBI outcomes.

RESULTSWe totally identified 16 reports. For low-dose patients, the pooled relative risks (RRs) for two clinical outcomes of death or a combination of death and severe disability were 0.95 (95% confidence interval (CI): 0.80 to 1.13) and 0.95 (95% CI: 0.83 to 1.09), respectively. The risks for infection and gastrointestinal bleeding were 0.85 (95% CI: 0.50 to 1.45) and 0.64 (95% CI: 0.15 to 2.70), respectively. For high-dose group, the pooled RR of death is 1.14 (95% CI: 1.06 to 1.21). The pooled RRs for infection and gastrointestinal bleeding for the high-dose patients were 1.04 (95% CI: 0.93 to 1.15) and 1.26 (95% CI: 0.92 to 1.75), respectively. For long-term use group, the pooled RRs for two clinical outcomes of death or a combination of death and severe disability were 0.98 (95% CI: 0.87 to 1.12) and 1.00 (95% CI: 0.90 to 1.11), respectively. The risks for infection and gastrointestinal bleeding were 0.88 (95% CI: 0.71 to 1.11) and 0.96 (95% CI: 0.35 to 2.66), respectively. For short-term use group, the pooled RR of death is 1.15 (95% CI: 1.07 to 1.23), and importantly the effects on infections were beneficial in terms of TBI patients suffering from CIRCI.

CONCLUSIONSThis meta-analysis suggests an increased risk of death for TBI patients on a high dose and short term of glucocorticoids compared with those on a low dose and long term, for whom a trend towards clinical improvement is evident. In addition, stress-does of GCs further decrease the pneumonia incidence in TBI patients suffering from CIRCI. A large-scale multicenter randomized controlled trial is warranted for testing (1) the efficacy of stress-dose GCs treatment in the sub-acute phase of TBI (4-21 days after initial trauma), when CIRCI is most likely to occur; (2) the hypothesis that stress-dose GCs could boost patients' stress function and ensure survival.

Adrenal Cortex Hormones ; deficiency ; Brain Injuries ; drug therapy ; mortality ; physiopathology ; Critical Illness ; Glucocorticoids ; therapeutic use ; Humans ; Hypothalamo-Hypophyseal System ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Time Factors

High-altitude hypoxia can induce physiological dysfunction and mountain sickness, but the underlying mechanism is not fully understood. Corticotrophin-releasing factor (CRF) and CRF type-i receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors. We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time- and dose-dependent manner, impaired or improved learning and memory, and anxiety-like behavioral change. Meanwhile, hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems, including suppression of growth and development, as well as inhibition of reproductive, metabolic and immune functions. In contrast, the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitude-hypoxia challenge, suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interactions between the genes and environment. All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction. This review extends these findings.
Altitude ; Animals ; Brain ; physiopathology ; Corticotropin-Releasing Hormone ; metabolism ; Hypothalamo-Hypophyseal System ; physiopathology ; Hypoxia ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Receptors, Corticotropin-Releasing Hormone ; metabolism ; Tibet

Stress or neuroendocrine response usually occurs soon after trauma, which is central to the maintenance of post-traumatic homeostasis. Immune inflammatory response has been recognized to be a key element both in the pathogenesis of post-traumatic complications and in tissue repair. Despite the existence of multiple and intricate interconnected neuroendocrine pathways, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system have been considered to be the most important in trauma. Although the short-term and appropriate activation of these stress responses is vital to the host's adaptation, prolonged duration and exaggerative magnitude of their activity leads to deleterious effects on immune function in trauma, causing immune dissonance. The overall appropriate and controlled activation and termination of the neuroendocrine responses that mediate the necessary physiological functions involved in maintaining and restoring homeostasis in the event of trauma are of critical importance. This review will describe the effects of some important neuroendocrine responses on immune system. Present evidences indicate that the neuroendocrine and immune systems form a cohesive and integrated early host response to trauma, and identify areas for further research to fully elucidate the regulatory role of neuroendocrine system in trauma.
Humans ; Hypothalamo-Hypophyseal System ; physiology ; Immune System ; physiology ; Parasympathetic Nervous System ; physiology ; Pituitary-Adrenal System ; physiology ; Stress Disorders, Post-Traumatic ; immunology ; physiopathology ; Sympathetic Nervous System ; physiology

The hypothesis 'whether subjects with attention-deficit/ hyperactivity disorder (ADHD), who showed under-reactivity of the hypothalamic-pituitary-adrenal (HPA) axis to stress, would make more commission errors in attention tasks', was examined. Forty-three boys, with ADHD, who visited the psychiatric outpatient clinic, at Kangbuk Samsung Hospital, were the subjects of this study. Both pre- and post-test morning saliva samples were collected from the patients at the Korean Educational Development Institute-Wechsler Intelligence Scale for Children (KEDI-WISC), and Tests of Variables of Attention (T.O.V.A.) performed. The Standard scores of the T.O.V.A were compared between the patients with decreases, or increases, in the salivary cortisol levels after the test. Decreases, or increases in the salivary cortisol levels after the test were shown in 28 and 15 patients, respectively. The patients with decreased cortisol levels after the test tended to make more commission errors in compared with those with increased cortisol levels. The patients with the decreased cortisol levels after test had more omission errors in the first quarter of the test, and more commission errors in the second half of the test compared to those with the increased cotisol levels. Subjects who show decreased salivary cortisol levels after stress make more commission errors in attention tests. This suggests that the blunted HPA axis response to stress is related to the impulsivity in patients with ADHD.
Attention ; Attention Deficit Disorder with Hyperactivity/*physiopathology/psychology ; Child ; Human ; Hydrocortisone/analysis ; Hypothalamo-Hypophyseal System/*physiopathology ; Intelligence ; Male ; Pituitary-Adrenal System/*physiopathology ; Saliva/chemistry

OBJECTIVETo study the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD).

METHODSOne hundred and twenty-eight boys with ADHD at ages of 6 to 14 years were enrolled. The diagnosis and grouping of ADHD were based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): ADHD-predominantly inattention type (ADHD-I, n=44), ADHD-predominantly hyperactive impulsivetype (ADHD-HI, n=32) and ADHD-combined type (ADHD-C, n=52). Thirty healthy boys served as the control group. Plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were measured by automatic particle enzyme immunoassay and electrochemiluminescence respectively at 8:00 am. The intelligence level was tested by Raven's standard progressive matrices.

RESULTSThe children with ADHD had lower IQ score (84.5 + or - 11.3) than the control group (94.6 + or - 12.4) (p<0.01). There were significant differences in the IQ score among the three ADHD subgroups (p<0.01). The IQ score in the ADHD-I and the ADHD-C groups was significantly lower than that in the control group. The mean plasma cortisol level in the ADHD group (226.5 + or - 129.1 nmol/L) was significantly lower than that in the control group (384.5 + or - 141.4 nmol/L) (p<0.01). The three ADHD subgroups showed significantly decreased plasma cortisol level compared with the control group (p<0.01). The plasma level of cortisol was the lowest in the ADHD-HI group (154.4 + or - 71.6 nmol/L), followed by the ADHD I group (219.4 + or - 117.7 nmol/L) and the ADHD-C group (258.3 + or - 136.4 nmol/L). There were no significant differences in plasma concentration of ACTH between ADHD and control children.

CONCLUSIONSIn the non-stress state, the HPA axis may be dysfunctional in children with ADHD, which may be attributed to the under reactivity of the HPA axis. Lower plasma cortisol has fewer impacts on the cognitive-behavior function, but it may closely be related to attention deficit, hyperactivity and impulsive behaviors.

Adolescent ; Adrenocorticotropic Hormone ; blood ; Attention Deficit Disorder with Hyperactivity ; physiopathology ; Child ; Electroencephalography ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; physiopathology ; Intelligence ; Male ; Pituitary-Adrenal System ; physiopathology

OBJECTIVETo study the effect of intrahepatic cholestasis of pregnancy (ICP) on the functions of the hypothalamic-pituitary-adrenocortical (HPA) axis and adrenal cortex in normal neonates.

METHODSDemographic characteristics, prenatal anxiety and depression, and perceived stress during delivery were investigated in 32 ICP women and 32 controls. The cord blood levels of cortisal, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate (DHEAS) were measured by the radioimmunity technique in normal neonates immediately after birth.

RESULTSThe scores of prenatal anxiety and depression in ICP women were significantly higher than those in controls (p<0.05 and p<0.01, respectively). There were no significant differences in the perceived stress during delivery between the two groups. The cord blood levels of cortisol and ACTH in neonates from ICP women were significantly lower (p<0.01), while the DHEAS level was significantly higher (p<0.01) than in neonates from controls. The DHEAS/ACTH ratio was significantly higher (p<0.01), while the cortisol/DHEAS ratio was significantly lower in the ICP group (p<0.01) than in the control group. The glycocholic acid level in ICP women was positively correlated with the DHEAS level in neonatal cord blood (r=0.47, p<0.01).

CONCLUSIONSThere may be a dissociation between cortisol and DHEAS in neonates with normal birth outcome from ICP women. ICP may result in a decreased responsiveness of HPA axis and an increased secretion of DHEAS by adrenal cortex in these neonates. This suggests that there might be dysfunction of the fetal zones of the adrenal cortex.

Adrenal Cortex ; physiopathology ; Adrenocorticotropic Hormone ; blood ; Adult ; Cholestasis, Intrahepatic ; physiopathology ; Dehydroepiandrosterone Sulfate ; blood ; Female ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; physiopathology ; Infant, Newborn ; Pituitary-Adrenal System ; physiopathology ; Pregnancy ; Pregnancy Complications ; physiopathology

OBJECTIVETo observe the therapeutic effect of acupuncture on kinetic insufficiency of kidney-qi and to study on the mechanism.

METHODSForty-four healthy professional sportsmen were randomly divided into an acupuncture group and a control group. They trained for 4 weeksq with regular detection. In the latter 2 weeks, the acupuncture group received scalp and body-acupuncture.

RESULTSThree weeks later, signs of insufficiency of kidney-qi appeared in most of the sportsmen in the two groups. Two weeks after treatment, in the acupuncture group the signs improved, and testosterone (T) and estradiol (E2) levels increased (P < 0.05); the symptoms did not significantly improve and the T and EZ levels decreased in the control group (P < 0.05).

CONCLUSIONAcupuncture therapy can regulate excitatory and inhibitory functions of the nervous system, improve symptoms of kinetic insufficiency of kidney-qi, and has regulative and repairing action on the sexual glands and adrenal gland.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Fatigue ; therapy ; Humans ; Hypothalamo-Hypophyseal System ; physiopathology ; Male ; Pituitary-Adrenal System ; physiopathology ; Qi ; Sports Medicine

Depression and insomnia are intimately related. Depressed patients usually manifest sleep discontinuity and early awakening, reduced or no slow wave sleep (SWS) and shortened latency of rapid eye movement (REM) sleep. These sleep abnormalities are very similar to those caused by over activated hypothalamic-pituitary-adrenal (HPA) axis with stress. Therefore, the animal models developed by post-traumatic stress disorder or chronic unpredictable mild stress could be used to evaluate drugs which have effects of both anti-depression and improvement of sleep quality, and to provide a more reliable platform for further studis on the mechanisms of depression and accompanied insomnia. This review mainly focuses on the typical features of sleep disturbance of depression, possible pathophysiological mechanisms, establishment of animal stress models and analysis of their abnormal sleep characteristics.
Animals ; Chronic Disease ; Depression ; physiopathology ; Depressive Disorder ; physiopathology ; Disease Models, Animal ; Humans ; Hypothalamo-Hypophyseal System ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Sleep ; physiology ; Sleep Initiation and Maintenance Disorders ; physiopathology ; Sleep, REM ; Stress Disorders, Post-Traumatic ; physiopathology ; Stress, Psychological ; physiopathology