Spinal cord injury results in a permanent neurological deficit due to tissue damage. Such a lesion is a barrier for “communication” between the brain and peripheral tissues, effectors as well as receptors. One of the primary goal s of tissue engineering is to bridge the spinal cord injury and re-establish the damaged connections. Hydrogels are biocompatible implants used in spinal cord injury repair. They can create a permissive environment and bridge the lesion cavities by providing a scaffold for the regeneration of neurons and their axons, glia and other tissue elements. The advantage of using artificial materials is the possibility to modify their physical and chemical properties in order to develop the best implant suitable for spinal cord injury repair. As a result, several types of hydrogels have been tested in experimental studies so far. We review our work that has been done during the last 5 years with various types of hydrogels and their applications in experimental spinal cord injury repair., A. Hejčl, P. Lesný, M. Přádný, J. Michálek, P. Jendelová, J. Štulík, E. Syková., and Obsahuje bibliografii a bibliografické odkazy
The rationale for the topical application of capsaicin and other vanilloids in the treatment of pain is that such compounds selectively excite and subsequently desensitize nociceptive neurons. This desensitization is triggered by the activation of vanilloid receptors (TRPV1), which leads to an elevation in intracellular free Ca2+ levels. Depending on the vanilloid concentration and duration of exposure, the Ca2+ influx via TRPV1 desensitizes the channels themselves, which may represent not only a feedback mechanism protecting the cell from toxic Ca2+ overload, but also likely contributes to the analgesic effects of capsaicin. This review summarizes the current state of knowledge concerning the mechanisms that underlie the acute capsaicin-induced Ca2+-dependent desensitization of TRPV1 channels and explores to what extent they may contribute to capsaicin-induced analgesia. In view of the polymodal nature of TRPV1, we illustrate how the channels behave in their desensitized state when activated by other stimuli such as noxious heat or depolarizing voltages. We also show that the desensitized channel can be strongly reactivated by capsaicin at concentrations higher than those previously used to desensitize it. We provide a possible explanation for a high incidence of adverse effects of topical capsaicin and point to a need for more accurate clinical criteria for employing it as a reliable remedy., L. Vyklický, K. Nováková-Toušová, J. Benedikt, A. Samad, F. Touška, V. Vlachová., and Obsahuje bibliografii a bibliografické odkazy
The circadian system controls the timing of behavioral and physiological functions in most organisms studied. The review addresses the question of when and how the molecular clockwork underlying circadian oscillations within the central circadian clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and the peripheral circadian clocks develops during ontogenesis. The current model of the molecular clockwork is summarized. The central SCN clock is viewed as a complex structure composed of a web of mutually synchronized individual oscillators. The importance of development of both the intracellular molecular clockwork as well as intercellular coupling for development of the formal properties of the circadian SCN clock is also highlighted. Recently, data has accumulated to demonstrate that synchronized molecular oscillations in the central and peripheral clocks develop gradually during ontogenesis and development extends into postnatal period. Synchronized molecular oscillations develop earlier in the SCN than in the peripheral clocks. A hypothesis is suggested that the immature clocks might be first driven by external entraining cues, and therefore, serve as “slave” oscillators. During ontogenesis, the clocks may gradually develop a complete set of molecular interlocked oscillations, i.e., the molecular clockwork, and become self-sustained clocks., A. Sumová, Z. Bendová, M. Sládek, R. El-Hennamy, K. Matějů, L. Polidarová, S. Sosniyenko, H. Illnerová., and Obsahuje bibliografii a bibliografické odkazy
The processing of species-specific communication signals in the auditory system represents an important aspect of animal behavior and is crucial for its social interactions, reproduction, and survival. In this article the neuronal mechanisms underlying the processing of communication signals in the higher centers of the auditory system - inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex (AC) - are reviewed, with particular attention to the guinea pig. The selectivity of neuronal responses for individual calls in these auditory centers in the guinea pig is usually low - most neurons respond to calls as well as to artificial sounds; the coding of complex sounds in the central auditory nuclei is apparently based on the representation of temporal and spectral features of acoustical stimuli in neural networks. Neuronal response patterns in the IC reliably match the sound envelope for calls characterized by one or more short impulses, but do not exactly fit the envelope for long calls. Also, the main spectral peaks are represented by neuronal firing rates in the IC. In comparison to the IC, response patterns in the MGB and AC demonstrate a less precise representation of the sound envelope, especially in the case of longer calls. The spectral representation is worse in the case of low-frequency calls, but not in the case of broad-band ca lls. The emotional content of the call may influence neuronal responses in the auditory pathway, which can be demonstrated by stimulation with time-reversed calls or by measurements performed under different levels of anesthesia. The investigation of the principles of the neural coding of species-specific vocalizations offers some keys for understanding the neural mechanisms underlying human speech perception., D. Šuta, J. Popelář, J. Syka., and Obsahuje bibliografii a bibliografické odkazy
The diffusion of neuroactive substances in the extracellular space (ECS) plays an important role in short- and long-distance communication between nerve cells and is the underlying mechanism of extrasynaptic (volume) transmission. The diffusion properties of the ECS are described by three parameters: 1. ECS volume fraction α (α = ECS volume/ total tissue volume), 2. tortuosity λ (λ2 = free /apparent diffusion coefficient), reflecting the presence of diffusion barriers represented by, e.g., fine neuronal and glial processes or extracellular matrix molecules and 3. nonspecific uptake k’. These diffusion parameters differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Moreover, diffusion barriers may channel the migration of molecules in the ECS, so that diffusion is facilitated in a certain direction, i.e. diffusion in certain brain regions is anisotropic. Changes in the diffusion parameters have been found in many physiological and pathological states in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances in the CNS and thus extrasynaptic transmission, neuron-glia communication, transmitter „spillover“ and synaptic cross-talk as well as cell migration, drug delivery and treatment., L. Vargová, E. Syková., and Obsahuje bibliografii a bibliiografické odkazy
The pathological potential of glial cells was recognized already by Rudolf Virchow, Santiago Ramon y Cajal and Pio Del Rio-Ortega. Many functions and roles performed by astroglia in the healthy brain determine their involvement in brain diseases; as indeed any kind of brain in sult does affect astrocytes, and their performance in pathological conditions, to a very large extent, determines the survival of the brain parenchyma, the degree of damage and neurological defect. Astrocytes being in general responsible for overall brain homeostasis are involved in virtually every form of brain pathology. Here we provide an overview of recent developments in identifying the role and mechanisms of the pathological potential of astroglia., A. Chvátal, M. Anděrová, H. Neprašová, I. Prajerová, L. Benešová, O. Butenko, A. Verkhratsky., and Obsahuje bibliografii a bibliografické odkazy
This review, which summarizes our findings concerning the long-term effects of pre-, peri- and postnatal factors affecting development, nociception and sensorimotor functions, focuses on three areas: 1) perinatal factors influencing nociception in adult rats were examined in rats with hippocampal lesions, after the administration of stress influencing and psychostimulant drugs (dexamethasone, indomethacine and methamphetamine); 2) the effect of pre- and early postnatal methamphetamine administration was shown to impair the development of sensorimotor functions tested in rat pups throughout the preweaning period; 3) the effect of extensive dorsal rhizotomy of the brachial plexus during the early postnatal period was studied with respect to neuropathic pain development and sensorimotor functions. The present study indicates that prenatal or neonatal stress, as well as various drugs, may disturb the development of the nociceptive system and cause long-term behavioral changes persisting to adulthood and that some types of neuropathic pain cannot be induced during the first two postnatal weeks at all. A mature nervous system is required for the development of the described pathological behaviors., R. Rokyta, A. Yamamotová, R. Šlamberová, M. Franěk, Š. Vaculín, L. Hrubá, B. Schutová, M. Pometlová., and Obsahuje bibliografii a bibliografické odkazy
The analysis of information coding in neurons requires methods that measure different properties of neuronal signals. In this paper we review the recently proposed measure of randomness and compare it to the coefficient of variation, which is the frequently employed measure of variability of spiking neuronal activity. We focus on the problem of the spontaneous activity of neurons, and we hypothetize that under defined conditions, spontaneous activity is more random than evoked activity. This hypothesis is supported by contrasting variability and randomness obtained from experimental recordings of olfactory receptor neurons in rats., L. Košťál, P. Lánský., and Obsahuje biblografii a biblografické odkazy
Transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel activated by capsaicin, a pungent substance from chili peppers. It is considered to act as an integrator of various physical and chemical nociceptive stimuli, as it can be gated by noxious heat (>43ºC), low pH (protons) and also by recently described endogenous lipids. The structure and function of TRPV1 receptors was vigorously studied, especially since its cloning in 1997. However, most of the research was pointed towards the role of TRPV1 receptors in the peripheral tissues. Mounting evidence now suggests that TRPV1 receptors on the central branches of dorsal root ganglion neurons in the spinal cord may play an important role in modulation of pain and nociceptive transmission. The aim of this short review was to summarize the knowledge about TRPV1 receptors in the spinal cord dorsal horn, preferentially from morphological and electrophysiological studies on spinal cord slices and from in vivo experiments., D. Špicarová, J. Paleček., and Obsahuje bibliografii a bibliografické odkazy
Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor – marked prolongation of ADs in all three age groups – suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures., P. Mareš, H. Kubová., and Obsahuje bibliografii a bibliografické odkazy