Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat.

Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting

Characterising the frequency response of impedance changes during evoked physiological activity in the rat brain

OBJECTIVE: Electrical impedance tomography (EIT) can image impedance changes associated with evoked physiological activity in the cerebral cortex using an array of epicortical electrodes. An impedance change is observed as the externally applied current, normally confined to the extracellular space is admitted into the conducting intracellular space during neuronal depolarisation. The response is largest at DC and decreases at higher frequencies due to capacitative transfer of current across the membrane. Biophysical modelling has shown that this effect becomes significant above 100 Hz. Recordings at DC, however, are contaminated by physiological endogenous evoked potentials. By moving to 1.7 kHz, images of somatosensory evoked responses have been produced down to 2 mm with a resolution of 2 ms and 200 μm. Hardware limitations have so far restricted impedance measurements to frequencies  2 kHz using improved hardware. APPROACH: Impedance changes were recorded during forepaw somatosensory stimulation in both cerebral cortex and the VPL nucleus of the thalamus in anaesthetised rats using applied currents of 1 kHz to 10 kHz. MAIN RESULTS: In the cortex, impedance changed by -0.04 ± 0.02 % at 1 kHz, reached a peak of -0.13 ± 0.05 % at 1475 Hz and decreased to -0.05 ± 0.02 % at 10 kHz. At these frequencies, changes in the thalamus were -0.26 ± 0.1%, -0.4 ± 0.15 % and -0.08 ± 0.03 % respectively. The signal-to-noise ratio was also highest at 1475 Hz with values of -29.5 ± 8 and -31.6 ±10 recorded from the cortex and thalamus respectively. Signficance: This indicates that the optimal frequency for imaging cortical and thalamic evoked activity using fast neural EIT is 1475 Hz

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.

Nurture versus nature: long-term impact of forced right-handedness on structure of pericentral cortex and basal ganglia.

Does a conflict between inborn motor preferences and educational standards during childhood impact the structure of the adult human brain? To examine this issue, we acquired high-resolution T1-weighted magnetic resonance scans of the whole brain in adult "converted" left-handers who had been forced as children to become dextral writers. Analysis of sulcal surfaces revealed that consistent right- and left-handers showed an interhemispheric asymmetry in the surface area of the central sulcus with a greater surface contralateral to the dominant hand. This pattern was reversed in the converted group who showed a larger surface of the central sulcus in their left, nondominant hemisphere, indicating plasticity of the primary sensorimotor cortex caused by forced use of the nondominant hand. Voxel-based morphometry showed a reduction of gray matter volume in the middle part of the left putamen in converted left-handers relative to both consistently handed groups. A similar trend was found in the right putamen. Converted subjects with at least one left-handed first-degree relative showed a correlation between the acquired right-hand advantage for writing and the structural changes in putamen and pericentral cortex. Our results show that a specific environmental challenge during childhood can shape the macroscopic structure of the human basal ganglia. The smaller than normal putaminal volume differs markedly from previously reported enlargement of cortical gray matter associated with skill acquisition. This indicates a differential response of the basal ganglia to early environmental challenges, possibly related to processes of pruning during motor development