Abstract Postural tachycardia syndrome (POTS) is defined by a heart rate increment of 30 beats/min or more within 10 minutes of standing or head-up tilt in the absence of orthostatic hypotension; the ...standing heart rate is often 120 beats/min or higher. POTS manifests with symptoms of cerebral hypoperfusion and excessive sympathoexcitation. The pathophysiology of POTS is heterogeneous and includes impaired sympathetically mediated vasoconstriction, excessive sympathetic drive, volume dysregulation, and deconditioning. POTS is frequently included in the differential diagnosis of chronic unexplained symptoms, such as inappropriate sinus tachycardia, chronic fatigue, chronic dizziness, or unexplained spells in otherwise healthy young individuals. Many patients with POTS also report symptoms not attributable to orthostatic intolerance, including those of functional gastrointestinal or bladder disorders, chronic headache, fibromyalgia, and sleep disturbances. In many of these cases, cognitive and behavioral factors, somatic hypervigilance associated with anxiety, depression, and behavioral amplification contribute to symptom chronicity. The aims of evaluation in patients with POTS are to exclude cardiac causes of inappropriate tachycardia; elucidate, if possible, the most likely pathophysiologic basis of postural intolerance; assess for the presence of treatable autonomic neuropathies; exclude endocrine causes of a hyperadrenergic state; evaluate for cardiovascular deconditioning; and determine the contribution of emotional and behavioral factors to the patient's symptoms. Management of POTS includes avoidance of precipitating factors, volume expansion, physical countermaneuvers, exercise training, pharmacotherapy (fludrocortisone, midodrine, β-blockers, and/or pyridostigmine), and behavioral-cognitive therapy. A literature search of PubMed for articles published from January 1, 1990, to June 15, 2012, was performed using the following terms (or combination of terms): POTS ; postural tachycardia syndrome , orthostatic ; orthostatic ; syncope ; sympathetic ; baroreceptors ; vestibulosympathetic ; hypovolemia ; visceral pain ; chronic fatigue ; deconditioning ; headache ; Chiari malformation ; Ehlers-Danlos ; emotion ; amygdala ; insula ; anterior cingulate ; periaqueductal gray ; fludrocortisone ; midodrine ; propranolol ; β-adrenergic ; and pyridostigmine . Studies were limited to those published in English. Other articles were identified from bibliographies of the retrieved articles.
Locus coeruleus Benarroch, Eduardo E.
Cell and tissue research,
07/2018, Letnik:
373, Številka:
1
Journal Article
Recenzirano
The locus coeruleus (LC) contains norepinephrine (NE)-synthesizing neurons that send diffuse projections throughout the central nervous system. The LC-NE system has a major role in arousal, attention ...and stress responses. In the brain, NE may also contribute to long-term synaptic plasticity, pain modulation, motor control, energy homeostasis and control of local blood flow. The LC is severely affected in neurodegenerative disorders including Parkinson disease (PD). Involvement of the noradrenergic neurons of the LC precedes that of dopaminergic neurons of the substantia nigra pars compacta and has been increasingly recognized as a potential major contributor to cognitive manifestations in early PD, particularly impaired attention. Abnormal noradrenergic signaling may also potentially contribute to motor manifestations of the disease.This makes the LC-NE system a major contributor to the pathobiology and potential target for therapy of PD.
Microglial cells are the immune cells in the CNS and represent approximately 10% of the total brain cell population. Their morphologic characterization by Pio del Rio-Hortega was first published ...almost a century ago, but the understanding of their function in the normal and injured CNS is still incomplete. Classically, microglia have been classified into 2 main types: "resting" microglia, with a ramified morphology, present in the uninjured CNS; and "activated" microglia, with an amoeboid morphology, present at the sites of injury. However, morphologic, molecular, and genetic studies indicate that this subdivision is a misleading oversimplification. Resting microglia actively survey their environment; activated microglia constitute a heterogeneous population that dynamically changes in phenotype depending on the type of stimulus and microenvironment, participating not only in mechanisms of injury but also in neuroprotection, repair, and circuit refinement in the CNS. The primary role of microglia is therefore to maintain cellular, synaptic, and myelin homeostasis both during development and normal function of the CNS and in response to CNS injury. Microglia have been implicated in mechanisms of CNS trauma, stroke, infection, demyelination, neoplasm, and neurodegeneration. Microglial dysfunction may also contribute to genetic neurobehavioral disorders, such as Rett syndrome. There are several comprehensive reviews on all these topics.
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises 4 members (HCN1-4) that are ...expressed in heart and nervous system. HCN channels are activated by membrane hyperpolarization, are permeable to Na+ and K+, and are constitutively open at voltages near the resting membrane potential. In many cases, activation is facilitated by direct interaction with cyclic nucleotides, particularly cyclic adenosine monophosphate (cAMP). The cation current through HCN channels is known as I(h); opening of HCN channels elicits membrane depolarization toward threshold for action potential generation, and reduces membrane resistance and thus the magnitude of excitatory and inhibitory postsynaptic potentials. HCN channels have a major role in controlling neuronal excitability, dendritic integration of synaptic potentials, synaptic transmission, and rhythmic oscillatory activity in individual neurons and neuronal networks. These channels participate in mechanisms of synaptic plasticity and memory, thalamocortical rhythms, and somatic sensation. Experimental evidence indicates that HCN channels may also contribute to mechanisms of epilepsy and pain. The physiologic functions of HCN channels and their implications for neurologic disorders have been recently reviewed.(1-10).
The pulvinar is the largest nucleus of the thalamus and has strong connectivity with the visual cortex. The pulvinar is a prototypic association nucleus that participates in reciprocal ...cortico-cortical interactions and promotes synchronized oscillatory activity in functionally related areas of the cortex. Via its connections with the superior colliculus (SC) and areas of the dorsal visual stream projecting to the posterior parietal cortex (PPC), the pulvinar is an important component of the visual attention network. Visual salience is likely an important function of the pulvinar. The pulvinar also participates in mechanisms of social cognition and blindsight. Unilateral lesions of the pulvinar result in a contralateral neglect syndrome resembling that resulting from lesions of the posterior parietal cortex. The pulvinar is susceptible to damage in epilepsy and prion disorders, and may contribute to cognitive and visual manifestations of Lewy body disease. The anatomy, physiology, and putative function of the pulvinar and its involvement in neurologic disorders have been the subject of comprehensive reviews.1-3
Brain-derived neurotrophic factor (BDNF) is the most ubiquitous and intensively studied member of the family of neurotrophins in the CNS. The transcriptional regulation of BDNF is complex and ...involves both epigenetic control and transcription factors. BDNF is produced "on demand" in response to neuronal activity from a precursor pro-BDNF that is transported and processed via the secretory pathway. The effects of mature BDNF are mediated by the tropomyosin-related kinase B (TrkB, tyrosine kinase B) receptor, which triggers phosphorylation cascades that promote protein synthesis, axonal growth, dendritic maturation, use-dependent synaptic plasticity, and neuroprotection. In contrast, pro-BDNF binds to the common neurotrophin receptor p75 super(NTR) and promotes apoptosis. BDNF can also be released from microglia and may bidirectionally affect inhibitory neurotransmission in the CNS. Disturbances in epigenetic control, transport, or signaling by BDNF may contribute to a variety of neurologic and psychiatric disorders, including Alzheimer disease (AD), Huntington disease (HD), spinocerebellar ataxia type 6 (SCA6), neuropathic pain, Rett syndrome, and depression, schizophrenia, and drug addiction. There are several recent reviews on these subjects.1-20
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