Dataset Information

Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study.

ABSTRACT: The onset of hepatic encephalopathy (HE) in liver failure is associated with high mortality; the underlying mechanism is undecided. Here we report that in an acute liver failure model employing intraperitoneal administration of thioacetamide in Sprague-Dawley rats, diffusion weighted imaging revealed a progressive reduction in apparent diffusion coefficient in the brain stem. Diffusion tensor imaging further showed that the connectivity between nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents in brain stem and rostral ventrolateral medulla (RVLM), the origin of sympathetic innervation of blood vessels, was progressively disrupted until its disappearance, coincidental with the irreversible cessation of baroreflex-mediated sympathetic vasomotor tone signifying clinically the occurrence of brain death. In addition, superoxide, nitric oxide, peroxynitrite and ammonia levels in the NTS or RVLM were elevated, alongside swelling of astroctytes. A scavenger of peroxynitrite, but not an antioxidant, delivered intracisternally reversed all these events. We conclude that nitrosative stress because of augmented peroxynitrite related to accumulation of ammonia and swelling of astrocytes in the NTS or RVLM, leading to cytotoxic edema in the brain stem and severance of the NTS-RVLM connectivity, underpins the defunct baroreflex-mediated sympathetic vasomotor tone that accounts for the high mortality associated with HE.

SUBMITTER: Tsai CY

PROVIDER: S-EPMC5228038 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study.

Tsai Ching-Yi CY Su Chia-Hao CH Chan Julie Y H JY Chan Samuel H H SH

Scientific reports 20170112

The onset of hepatic encephalopathy (HE) in liver failure is associated with high mortality; the underlying mechanism is undecided. Here we report that in an acute liver failure model employing intraperitoneal administration of thioacetamide in Sprague-Dawley rats, diffusion weighted imaging revealed a progressive reduction in apparent diffusion coefficient in the brain stem. Diffusion tensor imaging further showed that the connectivity between nucleus tractus solitarii (NTS), the terminal site ...[more]

PMID: 28079146

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Project description:Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy.

Dataset Information

Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study.

Publications

Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study.

Similar Datasets

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