Biomedical subjects

E Jankowska

Publications and source records attributed to E Jankowska.

At least 19 recordsLinked to original sources

PubMed2006

Neuronal relays in double crossed pathways between feline motor cortex and ipsilateral hindlimb motoneurones.

Coupling between pyramidal tract (PT) neurones and ipsilateral hindlimb motoneurones was investigated by recording from commissural interneurones interposed between them. Near maximal stimulation of either the left or right PT induced short latency EPSPs in more than 80% of 20 commissural interneurones that were monosynaptically excited by reticulospinal tract fibres in the medial longitudinal fascicle (MLF). The EPSPs were evoked at latencies that were only 1-2 ms longer than those of EPSPs evoked from the MLF, compatible with a disynaptic coupling between PT fibres and these commissural interneurones. EPSPs evoked by PT stimulation were frequently associated with IPSPs which either followed or preceded the EPSPs. The latencies of the IPSPs (on average about 1 ms longer than latencies of the earliest EPSPs) indicated that they were mediated via single additional inhibitory interneurones. Records from a sample of nine commissural interneurones from a different population (with monosynaptic input from group I and/or II muscle afferents, and disynaptically excited from the MLF) suggest that actions of PT fibres on such interneurones are weaker because only four of them were excited by PT stimuli and at longer latencies. By demonstrating disynaptic coupling between PT neurones and commissural interneurones via reticulospinal fibres, the results provide a direct demonstration of trisynaptic coupling in the most direct pathways between PT neurones and ipsilateral motoneurones, and thereby strengthen the proposal that the double crossed pathways between PT neurones and ipsilateral motoneurones might be used to replace crossed actions of damaged PT neurones.

Animals↗

PubMed2006

Same spinal interneurons mediate reflex actions of group Ib and group II afferents and crossed reticulospinal actions.

The aim of the study was to analyze interactions between neuronal networks mediating centrally initiated movements and reflex reactions evoked by peripheral afferents; specifically whether interneurons in pathways from group Ib afferents and from group II muscle afferents mediate actions of reticulospinal neurons on spinal motoneurons by contralaterally located commissural interneurons. To this end reticulospinal tract fibers were stimulated in the contralateral medial longitudinal fascicle (MLF) in chloralose-anesthetized cats in which the ipsilateral half of the spinal cord was transected rostral to the lumbosacral enlargement. In the majority of interneurons mediating reflex actions of group Ib and group II afferents, MLF stimuli evoked either excitatory or inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) or both EPSPs and IPSPs attributable to disynaptic actions by commissural interneurons. In addition, in some interneurons EPSPs were evoked at latencies compatible with monosynaptic actions of crossed axon collaterals of MLF fibers. Intracellular records from motoneurons demonstrated that both excitation and inhibition from group Ib and group II afferents are modulated by contralaterally descending reticulospinal neurons. The results lead to the conclusion that commissural interneurons activated by reticulospinal neurons affect motoneurons not only directly, but also by enhancing or weakening activation of premotor interneurons in pathways from group Ib and group II afferents. The results also show that both excitatory and inhibitory premotor interneurons are affected in this way and that commissural interneurons may assist in the selection of reflex actions of group Ib and group II afferents during centrally initiated movements.

Afferent Pathways↗

PubMed2005

Relative contribution of Ia inhibitory interneurones to inhibition of feline contralateral motoneurones evoked via commissural interneurones.

The aim of the study was to examine to what extent the crossed inhibition of hindlimb lumbar alpha-motoneurones is evoked via interneurones that mediate reciprocal inhibition between flexors and extensors (Ia inhibitory interneurones), and to what extent via other spinal interneurones. The crossed inhibition was evoked by reticulospinal and vestibulospinal tract fibres, stimulated in the contralateral medullary longitudinal fascicle and the lateral vestibular nucleus, respectively, or by group II muscle afferents in the contralateral quadriceps nerve. The components of the IPSPs recorded in motoneurones that were mediated by Ia inhibitory interneurones were identified by their depression following activation of Renshaw cells. Trisynaptic components of IPSPs of reticulospinal and vestibulospinal origin, and polysynaptic (but not trisynaptic) components of IPSPs from group II afferents were found to be depressed in the majority of the motoneurones, while disynaptic components, those due to direct actions of inhibitory commissural interneurones, were not depressed. These results indicate that the coordination of left and right hindlimb movements based on crossed inhibition from reticulospinal and vestibulospinal neurones, depends on the degree of activation of Ia inhibitory interneurones by muscle spindle afferents and on their inhibition by Renshaw cells. Our results also indicate that Ia inhibitory interneurones do not operate as last-order inhibitory interneurones in crossed trisynaptic pathways from group II afferents, even though they mediate inhibition evoked by interneurones in shared polysynaptic pathways of crossed flexor and extensor reflexes coactivated by group II and other high-threshold muscle, skin and joint afferents.

Animals↗

PubMed2005

How to enhance ipsilateral actions of pyramidal tract neurons.

We have shown previously that ipsilateral pyramidal tract (PT) neurons facilitate the actions of reticulospinal neurons on feline motoneurons (Edgley et al., 2004), which indicates that they might assist the recovery of motor functions after injuries of contralateral corticospinal neurons. Nevertheless, stimulation of ipsilateral PT fibers alone only rarely evoked any synaptic actions in motoneurons. The aim of this study was to investigate possible ways of enhancing such actions and of inducing more effective excitation and inhibition of motoneurons. The effects of stimulation of the ipsilateral PT were investigated after eliminating the spinal actions of contralateral PT fibers by hemisecting the spinal cord at a low thoracic level and were estimated from intracellular records from hindlimb motoneurons. Two measures were used to enhance PT actions. The first was to increase the probability of activation of reticulospinal neurons by mutual facilitation of actions of ipsilateral and contralateral PT neurons. The second was to enhance synaptic transmission between PT neurons and reticulospinal neurons, and in pathways between the reticulospinal neurons and motoneurons via commissural interneurons, by systemic application of a K+ channel blocker, 4-aminopyridine (4-AP). The results show that under favorable conditions, ipsilateral PT neurons may induce EPSPs and IPSPs in hindlimb motoneurons, or even action potentials, via the reticulospinal pathway. This study strengthens previous conclusions that ipsilateral PT neurons can potentially replace, at least to some extent, the actions of injured contralateral PT neurons. It also suggests that 4-AP might improve the progress of the recovery.

4-Aminopyridine↗

PubMed2005

Functional differentiation and organization of feline midlumbar commissural interneurones.

Interneurones interconnecting the two sides of the spinal cord (commissural interneurones) are critically important for interlimb coordination, but little is known about their organization. We have examined the inputs to commissural interneurones located in the midlumbar segments with projections to contralateral motor nuclei, aiming to determine whether they form distinct subpopulations. Based on intracellular records from 78 interneurones, two major non-overlapping subpopulations were identified: one monosynaptically excited by group II muscle afferents (n=10), the other monosynaptically excited by reticulospinal neurones (n=52). Monosynaptic input from group I muscle afferents and/or from vestibulospinal tract neurones was found in those with monosynaptic reticulospinal, but not group II input, and in a few other neurones (n=6). Only disynaptic input from these sources was found in the remaining 10 interneurones. Disynaptic excitatory input from ipsilateral and contralateral muscle afferents and from descending tracts was distributed less selectively and might mediate coexcitation of interneurones with monosynaptic afferent or descending input. The dominant disynaptic and polysynaptic input was, however, inhibitory. IPSPs were evoked from the descending tracts in a high proportion of the commissural interneurones that were monosynaptically excited by group II afferents (55%) and from group II afferents in a high proportion of the commissural interneurones that were monosynaptically excited by reticulospinal fibres (78%). This distribution suggests that the two subpopulations are activated differentially, rather than being coactivated, in either centrally initiated movements or reflex adjustments. This would be consistent with the previous demonstration that noradrenaline differentially affects commissural neurones of the two subpopulations.

Animals↗

PubMed2005

Survival analysis of Escherichia coli encapsulated in a hollow fiber membrane in vitro and in vivo: preliminary report.

The purpose of the observations was the viability and quality evaluation of E. coli bacteria encapsulated in hollow fiber membranes (HF) in short in vivo and in vitro experiments. A polypropylene, surface-modified hollow fiber was applied for immunoisolation of E. coli bacteria transfected with a green fluorescent protein (E. coli GFPI). The presence of GFP fluorescence of organisms was assessed with the use of flow cytometry. The E. coli GFPIs were then observed for the period of 5 days in in vitro experiments in the culture medium. A single IPTG (isopropyl beta-D-1-thiogalactopyranoside) induction of GFP gene appeared to be adequate for an expression of GFP protein for 5 days. The GFP expression values observed for E. coli GFPs encapsulated in HF during culture in different culture media were comparable. The survival of E. coli GFPIs encapsulated in HF after 1, 2, 4, or 5 days of subcutaneous implantation into mice was evaluated. The explanted E. coli GFPIs exhibited mean expression 603 +/- 17 (n = 32) units of fluorescence during the implantation period. The values obtained were comparable for selected days of observation. It was observed that the membranes applied ensured the bacteria growth within the HF's space only.

Animals↗

PubMed2004

Candidate interneurones mediating group I disynaptic EPSPs in extensor motoneurones during fictive locomotion in the cat.

In the present study we sought to find interneurones responsible for the group I-evoked disynaptic excitation of hindlimb extensor motoneurones that occurs during fictive locomotion. Locomotion was produced by stimulation of the mesencephalic locomotor region (MLR) in decerebrate paralysed cats in which activation of ankle extensor group I afferents evoked a disynaptic excitation of motoneurones during the extension phase of fictive locomotion. Extracellular recordings were used to locate interneurones fulfilling all, or five of the six following criteria: (i) weak or no response to stimulation of extensor group I afferents in the absence of locomotion; (ii) strong group I activation during locomotion; (iii) group I activation at monosynaptic latencies; (iv) strong group I activation during only the extensor phase of locomotion; and (v) antidromic activation from the extensor motor nuclei; but (vi) no antidromic activation from rostral spinal segments. Candidate excitatory interneurones were located in mid to caudal parts of the L7 segments in areas where monosynaptic field potentials were evoked by group I afferents, within 2 mm of the stimulation site in the ventral horn from which they were antidromically activated. All were activated during extension by stimulation of group I afferents in extensor nerves. In the absence of peripheral nerve stimulation, six of the seven candidate excitatory interneurones were rhythmically active with maximal activation during the extension phase of fictive locomotion. Rhythmic activity during extension was also seen in five additional interneurones located near candidate interneurones but not activated by group I strength stimulation of the tested nerves. We suggest that the lumbosacral interneurones located in the intermediate laminae that can be activated by extensor group I afferents during the extension phase are a previously unknown population of interneurones, and may mediate group I-evoked disynaptic excitation of extensor motoneurones. Their rhythmic activity suggests that they also provide central excitatory drive to extensor motoneurones during locomotion.

Afferent Pathways↗

PubMed2004

Ipsilateral actions of feline corticospinal tract neurons on limb motoneurons.

Contralateral pyramidal tract (PT) neurons arising in the primary motor cortex are the major route through which volitional limb movements are controlled. However, the contralateral hemiparesis that follows PT neuron injury on one side may be counteracted by ipsilateral of actions of PT neurons from the undamaged side. To investigate the spinal relays through which PT neurons may influence ipsilateral motoneurons, we analyzed the synaptic actions evoked by stimulation of the ipsilateral pyramid on hindlimb motoneurons after transecting the descending fibers of the contralateral PT at a low thoracic level. The results show that ipsilateral PT neurons can affect limb motoneurons trisynaptically by activating contralaterally descending reticulospinal neurons, which in turn activate spinal commissural interneurons that project back across to motoneurons ipsilateral to the stimulated pyramidal tract. Stimulation of the pyramids alone did not evoke synaptic actions in motoneurons but potently facilitated disynaptic EPSPs and IPSPs evoked by stimulation of reticulospinal tract fibers in the medial longitudinal fascicle. In parallel with this double-crossed pathway, corticospinal neurons could also evoke ipsilateral actions via ipsilateral descending reticulospinal tract fibers, acting through ipsilaterally located spinal interneurons. Because the actions mediated by commissural interneurons were found to be stronger than those of ipsilateral premotor interneurons, the study leads to the conclusion that ipsilateral actions of corticospinal neurons via commissural interneurons may provide a better opportunity for recovery of function in hemiparesis produced by corticospinal tract injury.

Animals↗

PubMed2004

Membrane for immunoisolation--properties before, and post implantation: preliminary report.

The membranes preventing tissue overgrowth as well as toxic influence on cells encapsulated within can be obtained modifying the polypropylene membranes by silanization. The influence of the silanization with different siloxanes on membrane transport properties was assessed before and post implantation. No change in cut-off values was observed. All of the modified membranes delayed tissue overgrowth of implant in mouse. Spectroscopic evaluation of the membrane material after 4, 7 days, 2 and 4 months of implantation revealed membrane material stability. We concluded that evaluated membranes with cells encapsulated within may be applied as the systems for delivery of biologically active substances.

Animals↗

PubMed2004

Two polymorphs of a covalent complex between papain and a diazomethylketone inhibitor.

The three-dimensional structure of two polymorphs of a ZLFG-CH2-papain covalent complex has been determined by X-ray crystallography. The structures indicate that: (i) the methylene carbon atom of the inhibitor is covalently bound to the Sgamma atom of Cys25 of papain; (ii) the hydrophobic S2 pocket formed by Pro68, Val133, Val157, and Asp158 is occupied by the inhibitor's phenylalanyl P2 side chain; (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. Comparison with similar structures suggests that in covalent complexes preservation of main chain-main chain interactions between the enzyme and the inhibitor may have higher priority than the P-S interactions.

Binding Sites↗

PubMed2003

Both dorsal horn and lamina VIII interneurones contribute to crossed reflexes from feline group II muscle afferents.

Previous studies have demonstrated that group II muscle afferents exert powerful actions on contralateral motoneurones and that these actions are mediated primarily via lamina VIII commissural interneurones. We examined whether dorsal horn interneurones also contribute to these actions, as they have been shown to contribute to the actions of group II afferents on ipsilateral motoneurones. We tested the susceptibility of IPSPs and EPSPs evoked from group II afferents in contralateral motoneurones to presynaptic inhibition as an indicator of the relative contribution of dorsal horn interneurones to these PSPs, since the monosynaptic activation of dorsal horn interneurones is more weakly and more briefly depressed by presynaptic inhibition than is the monosynaptic activation of lamina VIII and other intermediate zone and ventral horn interneurones. While the earliest components of IPSPs and EPSPs evoked by group II afferents were abolished by conditioning stimulation of group II afferents, consistent with them being evoked disynaptically by commissural interneurones, trisynaptic components of these PSPs were only partly reduced and are therefore attributed to dorsal horn interneurones. The same conditioning stimuli depressed the disynaptic excitation of lamina VIII commissural interneurones by group II afferents much less effectively than they depressed monosynaptic excitation, indicating that dorsal horn interneurones contribute to this disynaptic excitation. On the basis of these observations we conclude that that dorsal horn interneurones contribute to the late actions of group II muscle afferents on contralateral motoneurones through their disynaptic actions on commissural interneurones.

Animals↗

PubMed2003

Two-dimensional effects in laser-created plasmas measured with soft-x-ray laser interferometry.

Soft-x-ray laser interferograms of laser-created plasmas generated at moderate irradiation intensities (1 x 10(11)-7 x 10(12) W cm(-2)) with lambda=1.06 microm light pulses of approximately 13-ns-FWHM (full width at half maximum) duration and narrow focus (approximately 30 microm) reveal the unexpected formation of an inverted density profile with a density minimum on axis and distinct plasma sidelobes. Model simulations show that this strong two-dimensional hydrodynamic behavior is essentially a universal phenomena that is the result of plasma radiation induced mass ablation and cooling in the areas surrounding the focal spot.

Journal Article↗

PubMed2002

Differential presynaptic inhibition of actions of group II afferents in di- and polysynaptic pathways to feline motoneurones.

The aim of this study was to investigate differences in the effects of presynaptic inhibition of transmission from group II muscle afferents to neurones in the dorsal horn and in the intermediate zone and the consequences of these differences for reflex actions of group II afferents upon alpha-motoneurones. The degree of presynaptic inhibition was estimated from the degree of depression of monosynaptic components of population EPSPs (field potentials) evoked by group II muscle afferents in deeply anaesthetized cats. The decrease in the area of field potentials was considerably larger and longer lasting in the intermediate zone, where they were often obliterated, than in the dorsal horn, where they were reduced to about two-thirds. Presynaptic inhibition of field potentials evoked by other afferents at the same locations was much weaker. Intracellular records from alpha-motoneurones revealed that short latency EPSPs and IPSPs evoked from group II afferents are considerably reduced by conditioning stimuli that effectively depress intermediate zone field potentials of group II origin. The results of this study lead to the conclusion that strong presynaptic inhibition of transmission to intermediate zone interneurones allows a selective depression of disynaptic actions of group II muscle afferents on alpha- and gamma-motoneurones, mediated by these interneurones, and favours polysynaptic actions of these afferents.

Animals↗

PubMed2002

On organization of a neuronal network in pathways from group II muscle afferents in feline lumbar spinal segments.

The aim of the study was to verify the hypothesis that trisynaptic actions of group II muscle afferents upon motoneurones are, at least in part, mediated by dorsal horn interneurones exciting the same intermediate zone interneurones that are interposed in disynaptic pathways from group II afferents. Population EPSPs (field potentials) and responses of individual interneurones evoked by group II afferents in the dorsal horn and in the intermediate zone were analysed in order to assess the possibility of a causal relationship between them. When direct actions of group II afferents in the intermediate zone were abolished by presynaptic inhibition, distinct later components of field potentials and delayed interneuronal responses were induced at latencies 0.5-1 ms longer than those seen originally. Both the latency and a marked temporal facilitation define these later group II actions as being evoked disynaptically. Under the same conditions, single stimuli activated more than one half of dorsal horn interneurones, and the second and third stimuli activated all of these interneurones. Responses of dorsal horn interneurones preceded disynaptically evoked responses of intermediate zone interneurones. The study indicates that intermediate zone interneurones may be activated by group II afferents both directly and via dorsal horn interneurones and that synaptic actions of group II afferents upon these interneurones, and their subsequent actions upon motoneurones, may be modulated in parallel at the level of intermediate zone and dorsal horn interneurones.

Animals↗

PubMed2002

A comparison of postactivation depression of synaptic actions evoked by different afferents and at different locations in the feline spinal cord.

Postactivation depression of synaptic actions of group I and II muscle afferents and low threshold cutaneous afferents was compared with depression of actions of group Ia afferents on alpha-motoneurones in cats deeply anaesthetised with pentobarbital and alpha-chloralose. The depression was analysed on field potentials (population EPSPs). The degree of depression was evaluated by analysing changes in the monosynaptic components of the field potentials, in areas within 0.4- to 0.6-ms-long time windows from their onset. When intervals between successive stimuli used to evoke field potentials were reduced from 10 s to 0.4 s, the potentials evoked by Ia afferents in motor nuclei were depressed as described previously. Field potentials evoked by group II afferents and cutaneous afferents in the dorsal horn were similarly depressed. In contrast, monosynaptic components of field potentials evoked in the intermediate zone, by group I or II afferents, were only marginally affected. Postactivation depression of synaptic actions of group I afferents in the intermediate zone was not enhanced when test stimuli were applied 30-40 ms after a train of four conditioning stimuli. These observations indicate that the degree of postactivation depression may differ depending on the type of afferent. In addition, if postactivation depression depends on intrinsic properties of afferent terminals, differences in the degree of depression of postsynaptic potentials evoked by the same group of afferents at different locations may indicate that properties of terminals contacting different neurones may differ.

Afferent Pathways↗

PubMed2002

Spinal interneurones; how can studies in animals contribute to the understanding of spinal interneuronal systems in man?

The first part of this review deals with arguments that the essential properties and organization of spinal interneuronal systems in the cat and in man are similar. The second part is concerned with the possibility that some interneuronal systems may be responsible for motor disturbances caused by spinal cord injuries and that these interneurones may be defined. This possibility is discussed with respect to the hyperexcitability of alpha-motoneurones and the exaggeration of stretch reflexes in spastic patients. To this end, what is known about cat spinal interneurones and about the neuronal basis and pharmacological treatment of spasticity, is put together. Interneurones in di- and trisynaptic reflex pathways from group II muscle afferents are singled out, since they are depressed by the alpha(2) noradrenaline receptor agonists clonidine and tizanidine, which is a critical feature of interneurones expected to contribute to exaggerated stretch reflexes which are reduced by alpha(2) noradrenaline receptor agonists. Recent observations that reflex excitation of extensor motoneurones from group II afferents is enhanced in spastic patients and that the pathologically strong reflex actions of group II afferents are reduced by clonidine and tizanidine support this proposal. On the other hand, a lack of effect of clonidine and tizanidine upon other types of excitatory or inhibitory interneurones argues against any major contribution of such interneurones to the abnormally strong responses of alpha-motoneurones to muscle stretch.

Animals↗

PubMed2001

Spinal interneuronal systems: identification, multifunctional character and reconfigurations in mammals.

This review focuses on the flexibility of operation of spinal interneuronal networks and their multifunctional character in mammals. It concerns, in particular, two ways in which spinal interneuronal networks may be functionally reorganised, namely by modulating the synaptic actions of primary afferents by monoamines and by GABAergic presynaptic inhibition. The evidence will be reviewed for topographical and target-related differences in modulatory effects in various interneuronal networks and these will be related to differences in the intrinsic properties of different functional types of interneurones in these networks and to the role played by them.

Animals↗

PubMed2001

Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping.

The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the 'open interface' of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe 'conformational disease' is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.

Amino Acid Sequence↗