Biomedical subjects

T A Day

Publications and source records attributed to T A Day.

At least 19 recordsLinked to original sources

PubMed2006

Imaging of oral cavity cancer.

Despite many advances in surgical techniques, technology, radiation therapy, and chemotherapy, survival rates for head and neck cancer (HNCa) have not improved significantly in decades, with many patients being diagnosed at advanced disease stages. Adequate assessment of oral cavity malignancies is critical for appropriate planning of surgical, radiation, and chemotherapy treatment. Imaging modalities used to evaluate the oral cavity include plain radiography (panoramic radiography and intraoral radiography), nuclear medicine scintigraphy, ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). This review describes these imaging techniques and their utility, primarily CT and MRI.

Humans↗

PubMed2006

Role of calcium influx through voltage-operated calcium channels and of calcium mobilization in the physiology of Schistosoma mansoni muscle contractions.

We tested the hypothesis that voltage-operated Ca2+ channels mediate an extracellular Ca2+ influx in muscle fibres from the human parasite Schistosoma mansoni and, along with Ca2+ mobilization from the sarcoplasmic reticulum, contribute to muscle contraction. Indeed, whole-cell voltage clamp revealed voltage-gated inward currents carried by divalent ions with a peak current elicited by steps to +20 mV (from a holding potential of -70 mV). Depolarization of the fibres by elevated extracellular K+ elicited contractions that were completely dependent on extracellular Ca2+ and inhibited by nicardipine (half inhibition at 4.1 microM). However these contractions were not very sensitive to other classical blockers of voltage-gated Ca2+ channels, indicating that the schistosome muscle channels have an atypical pharmacology when compared to their mammalian counterparts. Futhermore, the contraction induced by 5 mM caffeine was inhibited after depletion of the sarcoplasmic reticulum either with thapsigargin (10 microM) or ryanodine (10 microM). These data suggest that voltage-operated Ca2+ channels do contribute to S. mansoni contraction as does the mobilization of stored Ca2+, despite the small volume of sarcoplasmic reticulum in schistosome smooth muscles.

Animals↗

PubMed2006

FasL gene therapy: a new therapeutic modality for head and neck cancer.

In this study, we investigated the in vitro and in vivo efficacy of Fas ligand (FasL) gene therapy for the treatment of head and neck cancer. Three head and neck squamous cell carcinoma (HNSCC) cell lines (SCC-1, SCC-12, and SCC-14a) were treated with the Fas agonist CH-11, a monoclonal antibody to the Fas receptor, or with a replication-incompetent adenovirus (AdGFPFasL) expressing a modified murine Fas ligand gene fused to green fluorescent protein (GFP). A replication-incompetent adenovirus containing the GFP gene alone was used as a control for viral transduction toxicity (AdGFP). Cell death was quantified using a tetrazolium-based (MTS) assay. Cells were analyzed by flow cytometry to determine the expression of adenoviral and Fas receptors on the surface of the cells. Our results showed that the head and neck cancer cell lines are resistant to cell death induction when treated with the anti-Fas monoclonal antibody CH-11. This resistance can be overcome with AdGFPFasL, which was able to induce cell death in all three cell lines. Apoptosis induction was demonstrated using Western blotting by evaluating poly(ADP-ribose) polymerase, and caspase 9 cleavages. In addition, intratumoral injections of AdGFPFasL into SCC-14a xenografts induced significant growth suppression of tumors, indicating that FasL gene therapy may provide a new efficient therapeutic modality for HNSCC that is worthy of a clinical trial.

Adenoviridae↗

PubMed2005

Neuropeptide signalling systems in flatworms.

Two distinct families of neuropeptides are known to endow platyhelminth nervous systems - the FMRFamide-like peptides (FLPs) and the neuropeptide Fs (NPFs). Flatworm FLPs are structurally simple, each 4-6 amino acids in length with a carboxy terminal aromatic-hydrophobic-Arg-Phe-amide motif. Thus far, four distinct flatworm FLPs have been characterized, with only one of these from a parasite. They have a widespread distribution within the central and peripheral nervous system of every flatworm examined, including neurones serving the attachment organs, the somatic musculature and the reproductive system. The only physiological role that has been identified for flatworm FLPs is myoexcitation. Flatworm NPFs are believed to be invertebrate homologues of the vertebrate neuropeptide Y (NPY) family of peptides. Flatworm NPFs are 36-39 amino acids in length and are characterized by a caboxy terminal GRPRFamide signature and conserved tyrosine residues at positions 10 and 17 from the carboxy terminal. Like FLPs, NPF occurs throughout flatworm nervous systems, although less is known about its biological role. While there is some evidence for a myoexcitatory action in cestodes and flukes, more compelling physiological data indicate that flatworm NPF inhibits cAMP levels in a manner that is characteristic of NPY action in vertebrates. The widespread expression of these neuropeptides in flatworm parasites highlights the potential of these signalling systems to yield new targets for novel anthelmintics. Although platyhelminth FLP and NPF receptors await identification, other molecules that play pivotal roles in neuropeptide signalling have been uncovered. These enzymes, involved in the biosynthesis and processing of flatworm neuropeptides, have recently been described and offer other distinct and attractive targets for therapeutic interference.

Animals↗

PubMed2004

Effect of naloxone-precipitated morphine withdrawal on c-fos expression in rat corticotropin-releasing hormone neurons in the paraventricular hypothalamus and extended amygdala.

Morphine withdrawal is characterized by physical symptoms and a negative affective state. The 41 amino acid polypeptide corticotropin-releasing hormone (CRH) is hypothesized to mediate, in part, both the negative affective state and the physical withdrawal syndrome. Here, by means of dual-immunohistochemical methodology, we examined the co-expression of the c-Fos protein and CRH following naloxone-precipitated morphine withdrawal. Rats were treated with slow-release morphine 50 mg/kg (subcutaneous, s.c.) or vehicle every 48 h for 5 days, then withdrawn with naloxone 5 mg/kg (s.c.) or saline 48 h after the final morphine injection. Two hours after withdrawal rats were perfused transcardially and their brains were removed and processed for immunohistochemistry. We found that naloxone-precipitated withdrawal of morphine-dependent rats increased c-Fos immunoreactivity (IR) in CRH positive neurons in the paraventricular hypothalamus. Withdrawal of morphine-dependent rats also increased c-Fos-IR in the central amygdala and bed nucleus of the stria terminalis, however these were in CRH negative neurons.

Amygdala↗

PubMed2004

A critical role for the parabrachial nucleus in generating central nervous system responses elicited by a systemic immune challenge.

Using Fos immunolabelling as a marker of neuronal activation, we investigated the role of the parabrachial nucleus in generating central neuronal responses to the systemic administration of the proinflammatory cytokine interleukin-1beta (1 microg/kg, i.a.). Relative to intact animals, parabrachial nucleus lesions significantly reduced the number of Fos-positive cells observed in the central amygdala (CeA), the bed nucleus of the stria terminalis (BNST), and the ventrolateral medulla (VLM) after systemic interleukin-1beta. In a subsequent experiment in which animals received parabrachial-directed deposits of a retrograde tracer, it was found that many neurons located in the nucleus tractus solitarius (NTS) and the VLM neurons were both retrogradely labelled and Fos-positive after interleukin-1beta administration. These results suggest that the parabrachial nucleus plays a critical role in interleukin-1beta-induced Fos expression in CeA, BNST and VLM neurons and that neurons of the NTS and VLM may serve to trigger or at least influence changes in parabrachial nucleus activity that follows systemic interleukin-1beta administration.

Animals↗

PubMed2004

Endoscopic ultrasonography in the diagnosis and staging of neoplasms of the head and neck.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive and highly accurate method of detecting mediastinal lymph-node metastases in gastrointestinal and lung cancer. Little information is available regarding the use of EUS-FNA to stage tumors in the head and neck region. This study reports experience with EUS in the diagnosis and staging of these tumors and their mediastinal spread. PATIENTS AND METHODS: The records of patients who underwent EUS for diagnosis and/or staging of head and neck tumors were reviewed. Referral criteria were suspected invasion of the esophagus by a lower-neck mass on cervical computed tomography (CT) or magnetic resonance imaging (MRI), or mediastinal lymphadenopathy > 10 mm on a chest CT. RESULTS: Thirty-two patients (23 men, nine women; mean age 65 years, range 44 - 80) were referred and underwent 35 EUS examinations. In one patient, EUS was not possible due to a benign esophageal stricture. In 17 patients with suspected esophageal invasion on CT scans, EUS demonstrated invasion of the esophagus in four cases and of the pleura in one; 12 tumors showed no visible invasion of adjacent structures. The other 17 examinations were carried out for suspected mediastinal metastatic disease. In eight cases, EUS-FNA confirmed metastatic disease, whereas only benign changes were shown in the other nine cases. EUS-FNA also provided the first tissue diagnosis in two primary tumors and identified malignancy in one patient with no CT suspicion of positive mediastinal lymph nodes. EUS avoided the need for more invasive investigations in all patients with mediastinal lymphadenopathy, and it changed the management in 12 of the 17 patients (71 %) with suspected esophageal invasion and in eight of the 17 patients (47 %) with suspected mediastinal disease. CONCLUSIONS: EUS with FNA provides a viable approach to the diagnosis and staging of tumors in the head and neck region when there is a suggestion of esophageal invasion on CT or MRI, or enlarged mediastinal lymph nodes. EUS with FNA may avoid the need for mediastinoscopy or other more invasive techniques for staging of these neoplasms.

Adult↗

PubMed2004

Differential involvement of rat medial prefrontal cortex dopamine receptors in modulation of hypothalamic-pituitary-adrenal axis responses to different stressors.

Recent investigations have implicated the medial prefrontal cortex (mPFC) in modulation of subcortical pathways that contribute to the generation of behavioural, autonomic and endocrine responses to stress. However, little is known of the mechanisms involved. One of the key neurotransmitters involved in mPFC function is dopamine, and we therefore aimed, in this investigation, to examine the role of mPFC dopamine in response to stress in Wistar rats. In this regard, we infused dopamine antagonists SCH23390 or sulpiride into the mPFC via retrodialysis. We then examined changes in numbers of cells expressing the c-fos immediate-early gene protein product, Fos, in subcortical neuronal populations associated with regulation of hypothalamic-pituitary-adrenal (HPA) axis stress responses in response to either of two stressors; systemic injection of interleukin-1 beta, or air puff. The D1 antagonist, SCH23390, and the D2 antagonist, sulpiride, both attenuated expression of Fos in the medial parvocellular hypothalamic paraventricular nucleus (mpPVN) corticotropin-releasing factor cells at the apex of the HPA axis, as well as in most extra-hypothalamic brain regions examined in response to interleukin-1 beta. By contrast, SCH23390 failed to affect Fos expression in response to air puff in any brain region examined, while sulpiride resulted in an attenuation of the air puff-induced response in only the mpPVN and the bed nucleus of the stria terminalis. These results indicate that the mPFC differentially processes the response to different stressors and that the two types of dopamine receptor may have different roles.

Adrenocorticotropic Hormone↗

PubMed2003

Descending pathways from the paraventricular nucleus contribute to the recruitment of brainstem nuclei following a systemic immune challenge.

Hypothalamic nuclei, particularly the paraventricular nuclei (PVN), are important brain sites responsible for central nervous system responses during an immune challenge. The brainstem catecholamine cells of the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM) have been shown to play critical roles in relaying systemic immune signals to the PVN. However, whilst it is well recognised that PVN divisions also innervate the NTS and VLM, it is not known whether descending PVN pathways can modulate the recruitment of brainstem cells during an immune challenge. Using systemic administration of the proinflammatory cytokine interleukin-1beta, in combination with Fos immunolabelling, we firstly investigated the effect of PVN lesions on NTS and VLM catecholamine and non-catecholamine cell responses. We found that ibotenic acid lesions of the PVN significantly reduced numbers of Fos-positive non-catecholamine, noradrenergic and adrenergic cells observable in the VLM and NTS after interleukin-1beta administration. We then investigated the origins of descending inputs to the VLM and NTS, activated by systemic interleukin-1beta, by mapping the distribution of Fos-positive retrogradely-labelled cells in divisions of the PVN after iontophoretically depositing choleratoxin-b subunit into the NTS or VLM one week prior to interleukin-1beta administration. We found that, after either NTS or VLM deposits, the majority of retrogradely-labelled Fos-positive cells activated by interleukin-1beta were localised in the medial and lateral parvocellular PVN divisions. Retrogradely-labelled Fos-positive cells were also observed in the NTS after VLM deposits, and in the VLM after NTS tracer deposits, suggesting reciprocal communication between these two nuclei after systemic interleukin-1beta. Thus the present study shows that the PVN has the capacity to modulate NTS and VLM responses after an immune challenge and that these may result from descending projections arising in the medial and lateral PVN divisions. These findings suggest that central nervous system responses to an immune challenge are likely to involve complex reciprocal connections between the PVN and the brainstem as well as between brainstem nuclei themselves.

Animals↗

PubMed2003

Systemic apomorphine alters HPA axis responses to interleukin-1 beta administration but not sound stress.

Apomorphine is a dopamine receptor agonist that was recently licensed for the treatment of erectile dysfunction. However, although sexual activity can be stressful, there has been little investigation into whether treatments for erectile dysfunction affect stress responses. We have examined whether a single dose of apomorphine, sufficient to produce penile erections (50 microg/kg, i.a.), can alter basal or stress-induced plasma ACTH levels, or activity of central pathways thought to control the hypothalamic-pituitary-adrenal axis in rats. An immune challenge (interleukin-1 beta, 1 microg/kg, i.a.) was used as a physical stressor while sound stress (100 dB white noise, 30 min) was used as a psychological stressor. Intravascular administration of apomorphine had no effect on basal ACTH levels but did substantially increase the number of Fos-positive amygdala and nucleus tractus solitarius catecholamine cells. Administration of apomorphine prior to immune challenge augmented the normal ACTH response to this stressor at 90 min and there was a corresponding increase in the number of Fos-positive paraventricular nucleus corticotropin-releasing factor cells, paraventricular nucleus oxytocin cells and nucleus tractus solitarius catecholamine cells. However, apomorphine treatment did not alter ACTH or Fos responses to sound stress. These data suggest that erection-inducing levels of apomorphine interfere with hypothalamic-pituitary-adrenal axis inhibitory feedback mechanisms in response to a physical stressor, but have no effect on the response to a psychological stressor. Consequently, it is likely that apomorphine acts on a hypothalamic-pituitary-adrenal axis control pathway that is unique to physical stressors. A candidate for this site of action is the nucleus tractus solitarius catecholamine cell population and, in particular, A2 noradrenergic neurons.

Adrenocorticotropic Hormone↗

PubMed2003

Medial prefrontal cortex suppression of the hypothalamic-pituitary-adrenal axis response to a physical stressor, systemic delivery of interleukin-1beta.

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.

Adrenocorticotropic Hormone↗

PubMed2003

Organization of the musculature of schistosome cercariae.

Phalloidin-fluorescein isothiocyanate staining of filamentous actin was used to identify muscle systems within the cercariae of Schistosoma mansoni. Examination of labeled cercariae by confocal scanning laser microscopy revealed distinct organizational levels of myofiber arrangements within the body wall, anterior cone, acetabulum, and esophagus. The body wall throughout showed a typical latticelike arrangement of outer circular and inner longitudinal myofibers, with an additional innermost layer of diagonal fibers in the anterior portion of the body. Circular and longitudinal fibers were also evident in the anterior organ and esophagus and, to some extent, the ventral acetabulum. Most striking was the striation of the cercarial tail musculature.

Animals↗

PubMed2002

Opposing roles for medial and central amygdala in the initiation of noradrenergic cell responses to a psychological stressor.

Psychological stressors trigger the activation of medullary noradrenergic cells, an effect that has been shown to depend upon yet-to-be-identified structures located higher in the brain. To test whether the amygdala is important in this regard, we examined the effects of amygdala lesions on noradrenergic cell responses to restraint, and also looked at whether any amygdala cells that respond to restraint project directly to the medulla. Ibotenic acid lesions of the medial amygdala completely abolished restraint-induced Fos expression in A1 and A2 noradrenergic cells. In contrast, lesions of the central amygdala actually facilitated noradrenergic cell responses to restraint. Tracer deposits in the dorsomedial (but not ventrolateral) medulla retrogradely labelled many cells in the central nucleus of the amygdala, but none of these cells expressed Fos in response to restraint. These data suggest for the first time that the medial amygdala is critical to the activation of medullary noradrenergic cells by a psychological stressor whereas the central nucleus exerts an opposing, inhibitory influence upon noradrenergic cell recruitment. The initiation of noradrenergic cell responses by the medial amygdala does not involve a direct projection to the medulla. Accordingly, a relay through some other structure, such as the hypothalamic paraventricular nucleus, warrants careful consideration.

Amygdala↗

PubMed2001

Influence of solar ultraviolet-B radiation on Antarctic terrestrial plants: results from a 4-year field study.

We examined the influence of solar ultraviolet-B radiation (UV-B; 280-315 nm) on the performance of Antarctic vascular plants (Colobanthus quitensis and Deschampsia antarctica) by placing filters that either absorbed or transmitted most solar UV-B over tundra along the Antarctic Peninsula for four consecutive growing seasons. The difference in biologically effective UV-B levels between our treatments was 65%, which was similar to the enhancement in ambient UV-B levels that appeared attributable to ozone depletion during the first 2 months of the growing season (November and December) at our site (62%). In both species, exposure to UV-B reduced vegetative growth, primarily through slower leaf elongation rates that led to shorter fully expanded leaves. In C. quitensis, exposure to UV-B also led to reductions in leaf longevity, branch production, cushion diameter growth, aboveground biomass, and thickness of the non-green cushion base and litter layer. Exposure to UV-B accelerated the development of reproductive structures and increased the number of panicles (D. antarctica) and capsules (C. quitensis) that reached maturity per unit of ground surface area covered by mother plants. However, this effect was offset by a tendency for these panicles and capsules to produce fewer spikelets and seeds. Ultimately, UV-B exposure did not effect the numbers of spikelets or seeds produced per unit of ground surface area. While seeds from plants exposed to UV-B tended to be lighter, germination rates were similar between UV-B treatments. The relative reductions in leaf elongation rates in D. antarctica attributable to UV-B exposure increased from the first (23%) through the fourth (43%) growing season, and relative reductions in leaf longevity in C. quitensis tended to increase from the first (9%) through the fourth (19%) growing season, suggesting that UV-B growth responses tended to be cumulative over successive years.

Antarctic Regions↗

PubMed2001

Stability and reproductive fitness of Schistosoma mansoni isolates with decreased sensitivity to praziquantel.

These studies are focused on schistosomes derived from human infections not cured by three successive doses of praziquantel that also produced infections in mice that were significantly more difficult to cure than infections with control worms. Half (three of six) of these isolates retained their decreased response to praziquantel after multiple passages through the life-cycle in the absence of therapeutic pressure. Two of the isolates, including the one initially least sensitive to praziquantel; reverted, to a sensitivity not significantly different from controls. For example, the EE6 isolate initially required 680 mg/kg praziquantel to affect a 50% reduction in worm load in murine infections, but after only six passages through the life cycle over 5 years this was reduced to 113 mg/kg, not different from control infections. The stability of some of the isolates and the reversion of others indicates that the biological or genetic factors conferring decreased praziquantel response varies among the isolates. The three isolates that retained decreased sensitivity to praziquantel all showed compromises in reproductive fitness in the laboratory, expressed most frequently as a decreased cercarial production from snails infected with those isolates compared to controls. For example, the total cercarial production of snails infected with the EE10 isolate was only 57% that of controls. The reversion of some of the isolates to a praziquantel sensitive state and the decreased reproductive fitness of those that did not revert suggest that there is some biological cost associated with the relative praziquantel insensitivity of these worms, which could help limit the impact of such isolates in the field. Infections with the less sensitive isolates also produced significantly less circulating schistosomal antigen in mice, suggesting that a decrease in the host immune response elicited by these worms could be one of the factors contributing to the diminished praziquantel efficacy.

Animals↗

PubMed2001

Peripheral withdrawal recruits distinct central nuclei in morphine-dependent rats.

This study examined if brain pathways in morphine-dependent rats are activated by opioid withdrawal precipitated outside the central nervous system. Withdrawal precipitated with a peripherally acting quaternary opioid antagonist (naloxone methiodide) increased Fos expression but caused a more restricted pattern of neuronal activation than systemic withdrawal (precipitated with naloxone which enters the brain). There was no effect on locus coeruleus and significantly smaller increases in Fos neurons were produced in most other areas. However in the ventrolateral medulla (A1/C1 catecholamine neurons), nucleus of the solitary tract (A2/C2 catecholamine neurons), lateral parabrachial nucleus, supramamillary nucleus, bed nucleus of the stria terminalis, accumbens core and medial prefrontal cortex no differences in the withdrawal treatments were detected. We have shown that peripheral opioid withdrawal can affect central nervous system pathways.

Animals↗

PubMed2001

Skull base reconstruction and rehabilitation.

This article separates skull base reconstruction into the surgical procedures available for immediate reconstruction of a small base defect and the secondary rehabilitative procedures that may be performed at a later date, usually for functional or cosmetic needs.

Bone Transplantation↗

PubMed2001

Medullary neurones regulate hypothalamic corticotropin-releasing factor cell responses to an emotional stressor.

Hypothalamic-pituitary-adrenal axis activation is a hallmark of the stress response. In the case of physical stressors, there is considerable evidence that medullary catecholamine neurones are critical to the activation of the paraventricular nucleus corticotropin-releasing factor cells that constitute the apex of the hypothalamic-pituitary-adrenal axis. In contrast, it has been thought that hypothalamic-pituitary-adrenal axis responses to emotional stressors do not involve brainstem neurones. To investigate this issue we have mapped patterns of restraint-induced neuronal c-fos expression in intact animals and in animals prepared with either paraventricular nucleus-directed injections of a retrograde tracer, lesions of paraventricular nucleus catecholamine terminals, or lesions of the medulla corresponding to the A1 or A2 noradrenergic cell groups. Restraint-induced patterns of neuronal activation within the medulla of intact animals were very similar to those previously reported in response to physical stressors, including the fact that most stressor-responsive, paraventricular nucleus-projecting cells were certainly catecholaminergic and probably noradrenergic. Despite this, the destruction of paraventricular nucleus catecholamine terminals with 6-hydroxydopamine did not alter corticotropin-releasing factor cell responses to restraint. However, animals with ibotenic acid lesions encompassing either the A1 or A2 noradrenergic cell groups displayed significantly suppressed corticotropin-releasing factor cell responses to restraint. Notably, these medullary lesions also suppressed neuronal responses in the medial amygdala, an area that is now considered critical to hypothalamic-pituitary-adrenal axis responses to emotional stressors and that is also known to display a significant increase in noradrenaline turnover during restraint. We conclude that medullary neurones influence corticotropin-releasing factor cell responses to emotional stressors via a multisynaptic pathway that may involve a noradrenergic input to the medial amygdala. These results overturn the idea that hypothalamic-pituitary-adrenal axis response to emotional stressors can occur independently of the brainstem.

Adrenocorticotropic Hormone↗