Neuroscience
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Different forms of electrical paroxysms in experimental animals mimic the patterns of absence seizures associated with spike-wave complexes at approximately 3 Hz and of Lennox-Gastaut seizures with spike-wave or polyspike-wave complexes at approximately 1.5-2.5 Hz, intermingled with fast runs at 10-20 Hz. Both these types of electrical seizures are preferentially generated during slow-wave sleep. Here, we challenge the hypothesis of a subcortical pacemaker that would account for suddenly generalized spike-wave seizures as well as the idea of an exclusive role of synaptic excitation in the generation of paroxysmal depolarizing components, and we focus on three points, based on multiple intracellular and field potential recordings in vivo that are corroborated by some clinical studies: (a) the role of neocortical bursting neurons, especially fast-rhythmic-bursting neurons, and of very fast oscillations (ripples, 80-200 Hz) in seizure initiation; (b) the cortical origin of both these types of electrical paroxysms, the synaptic propagation of seizures from one to other, local and distant, cortical sites, finally reaching the thalamus, where the synchronous cortical firing excites thalamic reticular inhibitory neurons and thus leads to steady hyperpolarization and phasic inhibitory postsynaptic potentials in a majority of thalamocortical neurons, which might explain the obliteration of signals from the external world and the unconsciousness during absence seizures; and (c) the cessation of seizures, whose cellular mechanisms have only begun to be investigated and remain an open avenue for research.
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The epithelial cells of the choroid plexuses secrete cerebrospinal fluid (CSF), by a process which involves the transport of Na(+), Cl(-) and HCO(3)(-) from the blood to the ventricles of the brain. The unidirectional transport of ions is achieved due to the polarity of the epithelium, i.e. the ion transport proteins in the blood-facing (basolateral) membrane are different to those in the ventricular (apical) membrane. The movement of ions creates an osmotic gradient which drives the secretion of H(2)O. ⋯ Aquaporin 1 mediates water transport at the apical membrane, but the route across the basolateral membrane is unknown. A model of CSF secretion by the mammalian choroid plexus is proposed which accommodates these proteins. The model also explains the mechanisms by which K(+) is transported from the CSF to the blood.
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Potassium-chloride cotransporters (KCCs) collectively play a crucial role in the function and development of both the peripheral and central nervous systems. KCC4 is perhaps the least abundant KCC in the adult mammalian brain, where its localization is unknown. In the embryonic brain, KCC4 mRNA is found in the periventricular zone, cranial nerves and choroid plexus [Eur J Neurosci 16 (2002) 2358]. ⋯ Co-staining of KCC4 with anti-MAP2, GFAP and CNPase revealed that KCC4 is expressed in peripheral neurons. Thus, KCC4 is expressed on the apical membrane of the choroid plexus, where it likely participates to K(+) reabsorption. KCC4 is also expressed in peripheral neurons, where its function remains to be determined.
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Aquaporin-4 (AQP4) is the major water channel in the CNS. Its expression at fluid-tissue barriers (blood-brain and brain-cerebrospinal fluid barriers) throughout the brain and spinal cord suggests a role in water transport under normal and pathological conditions. Phenotype studies of transgenic mice lacking AQP4 have provided evidence for a role of AQP4 in cerebral water balance and neural signal transduction. ⋯ In contrast, brain swelling and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid leak) edema caused by freeze-injury and brain tumor, probably due to impaired AQP4-dependent brain water clearance. AQP4-null mice also have markedly reduced acoustic brainstem response potentials and significantly increased seizure threshold in response to chemical convulsants, implicating AQP4 in modulation of neural signal transduction. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the CNS associated with altered brain water balance.
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Prostaglandin E2 (PGE2) produced in the medial preoptic region (MPO) in response to immune signals is generally accepted to play a major role in triggering the illness response, a complex of physiological and behavioral changes induced by infection or injury. Hyperalgesia is now thought to be an important component of the illness response, yet the specific mechanisms through which the MPO acts to facilitate nociception have not been established. However, the MPO does project to the rostral ventromedial medulla (RVM), a region with a well-documented role in pain modulation, both directly and indirectly via the periaqueductal gray. ⋯ In animals displaying behavioral hyperalgesia, the PGE2 microinjection activated on-cells, RVM neurons thought to facilitate nociception, and suppressed the firing of off-cells, RVM neurons believed to have an inhibitory effect on nociception. A large body of evidence has implicated prostaglandins in the MPO in generation of the illness response, especially fever. The present study indicates that the MPO also contributes to the hyperalgesic component of the illness response, most likely by recruiting the nociceptive modulating circuitry of the RVM.