Master of Science / Department of Animal Sciences and Industry / Timothy G. Rozell / Malnourished piglets that suffer from periweaning failure to thrive syndrome (PFTS) may show no signs of respiratory or enteric diseases but may have decreased feed intake and become debilitated after weaning. Euthanasia is a necessary component of swine production as it is sometimes the only option to alleviate suffering of piglets that are born with congenital defects or suffer from PFTS. Fifty-eight nursery-aged piglets were utilized in two experiments to evaluate blood parameter differences between healthy and unthrifty piglets and to compare euthanasia methods. Piglets were categorized into two health groups: healthy or unthrifty. During selection, blood was collected for analysis of blood parameters. Piglets were euthanized 24-32 hours after initial blood sampling and a second sample was collected for comparison. After euthanasia, piglets were necropsied for evaluation of euthanasia on pulmonary lesions. No significant difference in number of pulmonary lesions was found between health groups (P = 0.88). Healthy piglets had higher concentrations of glucose, ionized calcium and sodium, and greater pCO₂ than unthrifty piglets (P ≤ 0.05). Unthrifty piglets showed higher concentrations of hemoglobin and hematocrit (P = 0.0002) than healthy piglets. Piglets were assigned to one of two euthanasia methods to compare electrophysiological and behavioral parameters of hypobaric hypoxia and carbon dioxide gas. Two piglets at a time were euthanized for each method. One animal in the pair was fitted with electrocardiogram and electroencephalogram monitoring devices during euthanasia. Behavioral parameters were also recorded. The average treatment times were 27.4 ± 6.7 minutes for HH and 13.8 ± 5.1 minutes for CO2. Piglets euthanized via CO2 reached an isoelectric state faster than piglets euthanized via HH (P = 0.009). Behavioral observations revealed gasping in 100% of CO2 euthanized piglets during the first five minutes of treatment and only 28.6% of HH euthanized piglets during the same period. During HH, 57.1% of piglets became ataxic in the first five minutes while 76.9% of CO2¬ piglets became ataxic during the same period. Results of this trial indicate that HH may be a lower stress alternative to CO₂ as it causes fewer incidences of aversive behaviors in early stages of treatment.

Pulmonary hypertension syndrome (PHS) in broiler chickens adequately represents idiopathic pulmonary arterial hypertension (IPAH) in humans, a condition that affects 300 new patients each year in the US. The factors that trigger IPAH are poorly understood but an increase in reactive oxygen species in the circulation coincides with the onset of these conditions. Broiler chickens (n=583) were fed a control diet (CTL), containing 3,200 kcal of ME / kg of feed, 23% CP, 1.55% (wt / wt) Arginine (Arg) and 40 IU of VE (alpha-tochopherol) / kg of feed; a high-Arg diet (HA), CTL diet plus 0.8% (wt / wt) supplemental L-Arg HCl; or a high Arg and vitamin diet (AEC), the HA diet plus 200 IU ?-tochopherol / kg of feed and 500 mg of ascorbic acid / L of drinking water 500 mg ascorbic acid / L of water (exp. 1 and 2) or Kg feed (exp. 3). Supplemented broilers were either exposed to hypobaric hypoxia or had a primary bronchus occluded (PBO) to induce PHS. Also, medial thickness was assessed in male broiler and Leghorn (n =80) chickens fed a CTL diet and subjected to pulmonary artery occlusion (PAO). The results show that supplementation with Arg and VE plus VC have an additive effect on the velocity at which the pulmonary arterial pressure returned to basal levels in hypoxic chickens challenged with epinephrine. Also, supplementation increased xanthine oxidase (XO) activity in the vicinity of the pulmonary endothelium with no effect on NAD(P)H-oxidase activity or oxidative stress in hypoxic chickens subjected to PBO. These enzymes are upregulated in humans with IPAH. Furthermore, supplementation reduced pulmonary artery reactivity to phenylephrine in hypoxemic broilers. Unsupplemented broiler chickens had a lower specific lung weight compared to unsupplemented Leghorns. Hypoxemic broilers showed thicker resistant pulmonary arteries and were more hypertensive than hypoxemic Leghorns. Leghorns were more hypoxemic and resistant to PHS than broilers. In conclusion, Arg and VE plus VC show an additive effect in the improvement of cardiovascular performance of hypoxemic broilers as well as in restoring reactivity to phenylephrine in hypoxemic pulmonary rings. Also, supplementation shows an additive effect in restoring XO activity in hypoxic broilers. Leghorns had a better ventilation capacity and better pulmonary vasodilation capacity than broiler chickens.

Neurorehabilitation is a multidisciplinary rehabilitation process used in patients with neurological diseases. These patients have not only movement disorders but also cognitive and neurobehavioral problems as well as aphasias. Their rehabilitation is a long term process and the results are often unsatisfactory. Neuroplasticity - physiological basis for neurorehabilitation induces functional restitution or recovery after secondary brain damage. Various neuroprotective substances (e.g. erythropoietin - EPO) are tested to empower mechanisms of plasticity after brain injury. Preclinical studies testing efficacy of those substances in animal brain damage models are essential to prepare clinical trials. The aim of the study was to reveal the influence of EPO combined with rehabilitation on functional outcomes after global cerebral hypoxia. FIM (Functional independence measure) test was used for functional evaluation and Meilli test for visual memory of the patients who attended special program for rehabilitation in clinical part. Patients who came earlier had better prognosis than patients who came later. In experimental part three-months old male Wistar albino rats were exposed to hypobaric hypoxia for 60 minutes in an experimental chamber, simulating an altitude of 8000 m. Half of the animals received...

Neurorehabilitation is a multidisciplinary rehabilitation process used in patients with neurological diseases. These patients have not only movement disorders but also cognitive and neurobehavioral problems as well as aphasias. Their rehabilitation is a long term process and the results are often unsatisfactory. Neuroplasticity - physiological basis for neurorehabilitation induces functional restitution or recovery after secondary brain damage. Various neuroprotective substances (e.g. erythropoietin - EPO) are tested to empower mechanisms of plasticity after brain injury. Preclinical studies testing efficacy of those substances in animal brain damage models are essential to prepare clinical trials. The aim of the study was to reveal the influence of EPO combined with rehabilitation on functional outcomes after global cerebral hypoxia. FIM (Functional independence measure) test was used for functional evaluation and Meilli test for visual memory of the patients who attended special program for rehabilitation in clinical part. Patients who came earlier had better prognosis than patients who came later. In experimental part three-months old male Wistar albino rats were exposed to hypobaric hypoxia for 60 minutes in an experimental chamber, simulating an altitude of 8000 m. Half of the animals received...

The current research work aims at the development of Biomedical Neuroengineering tools (Biotechnologies) for the in-depth functional study, rapid diagnosis, continuous monitoring and well-timed management of acute and chronic brain disorders, of individuals that are subjected to or suffer from any kind of systemic hypoxaemia or more localized brain hypoxia; as well as the functional assessment and continuous control of adaptability during the training of “altinauts” and generally of individuals that practice activities and function within environments of increased visual-cognitive-motor response demands (a type of brain “stress test”). For this purpose, we subject the entire visuocognitive system, from the elementary sensory to the most complex cognitive level, to an experimental test of categorical discrimination of complex visuocognitive stimuli, following ultra-rapid visual stimulation that leads to a motor response upon categorization of targets (images of animals elicit productive responses) and to its suppression upon categorization of nontargets (images of nonanimals elicit inhibitory responses). The oscillatory electro-physiological responses that are concurrently recorded at the occipital-temporal-parietal brain areas are analyzed in the time-domain (<20Hz) and in the joint time-frequency domain broadband (1-60Hz) with the Continuous Wavelet Transform that optimizes the multiresolution analysis of the high frequency (≥20Hz) γ-band oscillatory activity. This visuocognitive categorization test takes place in normoxaemic as well as hypoxaemic conditions (monitored reduction in the blood oxygen saturation from ≥97% to around 80% under conditions of hypobaric hypoxia within a hypobaric chamber), in order to assess electrophysiological markers that can detect and capture in the most sensitive and dynamic way even so transient, short-living and rather mild changes in brain function. The statistical parametric analysis of the time-frequency maps and the generalized, statistically safer, method of analysis of variance have established as the most sensitive and reliable the following markers: the major deflections of the evoked potentials, the phase-coherence factor of the oscillations across single-trials and the elicited energy of the evoked/phase-locked and the induced/total oscillatory activity. These electrophysiological markers in conjunction with psychometric tests allow for the investigation of the stages/levels of the decline as well as of the compensatory reserves in the visual-perceptive and cognitive-mental brain functions in order to determine the functional sensitivity thresholds of different brain functions to hypoxia. They open up the way for the functional characterization, the diagnosis and monitoring of brain insults or other acute and chronic pathological brain conditions. / Η παρούσα ερευνητική εργασία στοχεύει στην ανάπτυξη εργαλείων Βιοϊατρικής Νευρομηχανικής (Βιοτεχνολογίες) για την σε βάθος λειτουργική μελέτη, ταχεία διάγνωση, συνεχή παρακολούθηση και έγκαιρη αντιμετώπιση οξέων και χρόνιων εγκεφαλικών διαταραχών, ατόμων που υπόκεινται σε ή πάσχουν από οιαδήποτε μορφή συστηματικής υποξαιμίας ή πιο εντοπισμένης εγκεφαλικής υποξίας, καθώς και για την λειτουργική αξιολόγηση και το συνεχή έλεγχο της προσαρμοστικότητας κατά την εξάσκηση των «υψιβατών», και γενικότερα ατόμων που ασκούν δραστηριότητες και λειτουργούν μέσα σε περιβάλλοντα αυξημένων οπτικο-γνωστικο-κινητικών απαιτήσεων (ένα είδος «στρες τεστ» για τον εγκέφαλο). Για το σκοπό αυτό υποβάλλουμε ολόκληρο το οπτικογνωστικό σύστημα, από το στοιχειώδες αισθητηριακό έως το πιο πολύπλοκο νοητικό επίπεδο, σε μια πειραματική δοκιμασία κατηγορικής διάκρισης σύνθετων οπτικογνωστικών ερεθισμάτων, μετά από υπερταχεία οπτική διέγερση που οδηγεί στην έκλυση κινητικής απάντησης κατά την κατηγοριοποίηση στόχων (εικόνες «ζώων» εκλύουν παραγωγικές αποκρίσεις) και στην καταστολή της κατά την κατηγοριοποίηση μη-στόχων (εικόνες «μη-ζώων» εκλύουν ανασταλτικές αποκρίσεις). Οι ταλαντωτικές ηλεκτροφυσιολογικές αποκρίσεις που συγχρόνως καταγράφονται στις ινιακές-κροταφικές-βρεγματικές περιοχές του εγκεφάλου αναλύονται στο πεδίο του χρόνου (<20Hz) και στο συζευγμένο χρονοφασματικό πεδίο ευρυζωνικά (1-60Hz) με το συνεχή μετασχηματισμό του κυματίου που βελτιστοποιεί την πολυφασματική ανάλυση της υψίσυχνης (≥20Hz) γ-ταλαντωτικής δραστηριότητας. Αυτή η δοκιμασία οπτικογνωστικής κατηγοριοποίησης λαμβάνει χώρα τόσο σε νορμοξαιμικές όσο και υποξαιμικές συνθήκες (ελεγχόμενη μείωση στον κορεσμό του αίματος σε οξυγόνο από ≥97% γύρω στο 80% για 15 λεπτά κάτω από συνθήκες υποβαρικής υποξίας μέσα σε υποβαρικό θάλαμο), προκειμένου να ελέγξουμε ηλεκτροφυσιολογικούς δείκτες που μπορούν να ανιχνεύσουν και να συλλάβουν με τον πιο ευαίσθητο και δυναμικό τρόπο ακόμη και τόσο βραχύβιες και σχετικά ήπιες μεταβολές της εγκεφαλικής λειτουργίας. Η στατιστική παραμετρική ανάλυση των χρονοφασματικών χαρτών και η γενικευμένη, στατιστικά πιο ασφαλής, μέθοδος ανάλυσης των διακυμάνσεων ανέδειξαν ως πλέον ευαίσθητους και αξιόπιστους τους ακόλουθους δείκτες: τις κύριες αιχμές των προκλητών δυναμικών, τον παράγοντα φασικής συνάφειας των ταλαντώσεων μεταξύ των μοναδιαίων καταγραφών και την εκλυόμενη ενέργεια των προκλητών/φασικά-κλειδωμένων και επαγόμενων/ολικών ταλαντώσεων. Οι ηλεκτροφυσιολογικοί αυτοί δείκτες σε συνδυασμό με ψυχομετρικές δοκιμασίες επιτρέπουν τη διερεύνηση των σταδίων/επιπέδων κάμψης καθώς και των αποθεμάτων αντιρρόπησης των οπτικο-αντιληπτικών και γνωστικών-νοητικών λειτουργιών του εγκεφάλου για τον καθορισμό των λειτουργικών ουδών ευαισθησίας διάφορων εγκεφαλικών λειτουργιών στην υποξία. Ανοίγουν μάλιστα το δρόμο. για το λειτουργικό χαρακτηρισμό, τη διάγνωση και την παρακολούθηση εγκεφαλικών προσβολών ή άλλων οξέων και χρόνιων παθολογικών καταστάσεων του εγκεφάλου.