Coeruleus delirium

Clonidine and dexmedetomidine are two α2-adrenoreceptors agonists available for the intensivist in the clinical practice. The affinity of dexmedetomidine is eight times greater than clonidine affinity for the α2 receptors. Their main effect is sedation. They act by inhibition of noradrenaline release in the locus coeruleus in the brainstem. α2-agonists are used primarily for sedation, analgesia, and management of delirium. Nowadays, dexmedetomidine application is increasing in critically ill patients showing a good safety...

Neuroinflammatory disorders preferentially impair the higher cognitive and executive functions of the prefrontal cortex (PFC). This includes such challenging disorders as delirium, perioperative neurocognitive disorder, and the sustained cognitive deficits from "long-COVID" or traumatic brain injury. There are no FDA-approved treatments for these symptoms; thus, understanding their etiology is important for generating therapeutic strategies. The current review describes the molecular rationale for why PFC circuits are especially vulnerable to inflammation, and how α2A-adrenoceptor (α2A-AR) actions throughout the nervous and immune systems can benefit the circuits in PFC needed for higher cognition...

Delirium is a brain state involving severe brain dysfunction affecting cognitive and attentional capacities. Our opinion statement review aims to elucidate the relationship between abnormal arousal and locus coeruleus (LC) activity in cognitive dysfunction and inattention in delirium states. We propose (1) that enhanced noradrenaline release caused by altered arousal in hyperactive delirium states leads to increased noradrenergic transmission within the LC and subcortical and cortical brain regions including the prefrontal cortex and hippocampus, thus affecting how attention and cognition function...

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes...

Locus coeruleus (LC)-derived noradrenaline is important in cognition and decreases with age, but the impact of prior noradrenaline deficiency on vulnerability to inflammation-induced acute cognitive dysfunction is unclear. Here we assessed whether noradrenergic depletion, in female mice, impacted upon inflammation, locomotor activity and working memory directly after acute systemic immune challenge with bacterial lipopolysaccharide (LPS), a paradigm we have previously used to capture delirium-like acute cognitive deficits...

Delirium is an acute neuropsychiatric syndrome characterized by acute-onset global cognitive deficits, perceptual and behavioural disturbances affecting mainly elderly subjects with underlying medical or surgical conditions. The pathophysiology of delirium is complex and inflammation is a relevant precipitant factor of this syndrome, although it remains unclear how acute systemic inflammation induces the clinical picture of delirium. The central nervous system is able to detect peripheral infection or tissue destruction through circulating immune mediators and neural ascending signs...

The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves...

Consciousness (Latin conscientia "moral conscience"), according to the English philosopher John Locke (1632-1704) [103], is the awareness of all that occurs in the mind of a person, whereas the American philosopher John Searle (2000) defined it as "inner qualitative, subjective states and processes of awareness". In modern science it is defined as a continuous state of full awareness of the Self and one's relationship to the external and internal environment, describing the degree of wakefulness in which an organism recognizes stimuli...

Patients in the intensive care unit frequently experience delirium, anxiety, and agitation, with a variety of treatments used. This article discusses the role of an alpha-adrenoceptor agonist, dexmedetomidine, and its clinical relevance and advantages for the agitated patient.

The authors investigated whether war-related posttraumatic stress disorder (WR-PTSD) is associated with a postmortem change in neuronal counts in the locus coeruleus (LC) since enhanced central nervous system (CNS) noradrenergic postsynaptic responsiveness has been previously shown to contribute to PTSD pathophysiology. Using postmortem neuromorphometry, the number of neurons in the right LC in seven deceased elderly male veterans was counted. Three veterans were classified as cases of probable or possible WR-PTSD...

The presence of a high number of Lewy bodies--the morphological marker of Parkinson's disease--in the cerebral cortex of some cases of dementia has been frequently observed in association to Alzheimer type lesions (mainly senile plaques) and changes in the substantia nigra, that may be held responsible for the frequently associated symptoms of parkinsonism. The term "dementia with Lewy body" (DLB) has recently been suggested by a consensus conference and indicates that the pathogenetic mechanism of the dementia remains poorly understood...

The ethanol withdrawal syndrome includes anxiety as a prominent symptom. Because the extent that specific regions of brain are critical to the generation of this emotional state is unknown, Fos-like immunoreactivity (Fos-LI) was used to associate specific regions of the rat brain with the anxiety component of the ethanol withdrawal syndrome exacerbated by an air puff challenge in rats. Chronic ethanol liquid diet was administered intragastrically for 4 days or by having the rats consume the diet for 14 days...

We reviewed 7 cases with posterior fossa structural abnormalities (3 tumors, 2 megacisterna magna and 2 Dandy-Walker syndrome) presenting with neuropsychiatric symptomatology. Derangement in the balance of dopamine, serotonin and noradrenergic networks has been implicated in the pathogenesis of schizophrenia, affective and even personality disorders. Disruption of the cerebellar output to mesial dopaminergic areas, locus coeruleus and raphe nuclei, or deafferentation of the thalamolimbic circuits by a cerebellar lesion may lead to behavioral changes...

BACKGROUND: The prevalence of psychotic phenomena in confirmed Alzheimer's disease (AD) and their potential neuropathological correlates have rarely been the subject of prospective investigation. METHOD: Psychopathological disturbances were recorded prospectively according to the Geriatric Mental State Schedule and the CAMDEX: The frequency of these phenomena and neuropathological changes were examined in 56 patients with definite AD. RESULTS: Hallucinations had been documented in 13 patients, paranoid delusions in 9 and delusional misidentification (e...

Ethanol dependence was induced i Wistar male rats by administration of ethanol by gavage for 5 days in 3 fractional doses. Clonidine (0.1 mg/kg ip) strongly reduced the withdrawal syndrome. Bilateral lesions in the nucleus locus coeruleus were also able to decrease several withdrawal signs. Our data indicate that drugs decreasing activity of noradrenergic brain neurons might be useful in treatment of ethanol dependence.

Fifteen cases meeting the diagnostic criteria for presbyophrenia are reported and compared with a control sample of patients suffering from dementia. The presbyophrenic patients exhibited more elevated mood, more hyperactivity, more disorientation, and had lower information scores than the controls. Traditional explanations of 'presbyophrenic behaviour' such as delirium, pathoplastic effect of personality, or superimposed cerebrovascular disease are not adequate. Instead, presbyophrenia may constitute a sub-type of dementia characterised by severe atrophy of the locus coeruleus, marked impairment of noradrenergic transmission, and uninhibited behaviour...

The results of clinical and polysomnographical examinations on 11 Japanese Rett syndrome cases were summarized to substantiate further our previous results regarding the pathophysiology of the disease. It was concluded that the disease starts early in infancy and takes a progressive course. Each characteristic symptom appears in an orderly sequence which is thought to reflect the sequential systemic involvement of certain neuronal systems. Based on the characteristic symptoms and signs, and polysomnographical studies, we speculated that the initial lesion was the locus coeruleus with a hypoactive noradrenergic system combined with other hypoactive monoaminergic systems, including those of serotonin and dopamine, occurring along with the early developmental course...

The diagnosis of Alzheimer's disease (AD) was verified at post-mortem examination in 46 patients (9 male: 37 female; mean age 83.6 +/- 6.5 years) from a prospective clinical study. Compared to 10 age-matched controls, the total AD group showed a significant neuronal loss in the locus coeruleus, dorsal raphe nucleus, substantia nigra and in the basal nucleus of Meynert. Twelve patients (1 male: 11 female) had experienced symptoms of depression. These patients had significantly lower neuronal counts in the locus coeruleus, but less severe cell loss in the basal nucleus of Meynert compared to the AD patients without depression...