Δράση του αντιοξειδωτικού παράγοντα U-74389G σε πειραματικό πρότυπο ενδοεγκεφαλικού αιματώματος σε χοίρο: προσδιορισμός παραμέτρων φλεγμονής και σημαντικών ενζύμων

Spontaneous intracerebral haemorrhage (ICH) represents a partially understoodcerebrovascular disease of high incidence, morbidity and mortality, accounting for 10-15% of allstrokes. In my study, I investigated the pathophysiological changes that follow intracerebralhaematoma induction on a porcine model of ICH. The study focused on the determination ofchanges in tumour necrosis factor α (TNF-α) and interleukin 1 (IL-1) the first 4 and 24 hrs ofICH as well as the changes of the crucial enzymes adenosinetriphosphatases (ATPases), incombination with a study of the effectiveness of the lazaroid antioxidant U-74389G. Regardingboth TNF-α and IL-1, statistically significant increase was observed in the ipsilateral side of thehaematoma as early as 4 hrs and decrease again 24 hrs after the onset. U-74389G whenadministered resulted in statistically significant decrease of TNF-α, (at the heamatoma site incomparison to the controls) and non statistically significant decrease of IL-1 when compared tothe controls. Regarding the ATPases, my study demonstrated that the examined ICH model doesnot cause a decrease in Na+,K+-ATPase activity (the levels of which are responsible for verylarge part of neuronal energy expenditure) in the perihaematomal basal ganglia territory, nor achange in the activity of Mg2+-ATPase. The administration of U-74389G (an establishedneuroprotectant) in this ICH model revealed an injury specific type of behavior, that could beconsidered as neuroprotective.I also investigated the role of acetylocholinesterase (AChE; a crucial membrane boundenzyme involved in cholinergic neurotransmission) in the same porcine model of spontaneousICH, with a focus on the first 4 and 24 hrs following the lesion’s induction, in combination witha study of the effectiveness of the lazaroid antioxidant U- 74389G administration. My studydemonstrates the activation of AChE activity following U-74389G administration. The lazaroidU-74389G seems to be an established neuroprotectant and this is the first report of its supportingrole in the enhancement of cholinergic response to the induction of ICH.Η αυτόματη ενδοεγκεφαλική αιμορραγία (ΑΕΕ), είναι μια μερικώς κατανοητή αγγειακήεγκεφαλική νόσος, χαρακτηριζόμενη από υψηλή επίπτωση θνητότητα και θνησιμότητα ,αποτελεί δε το 10-15% όλων των αγγειακών εγκεφαλικών επεισοδίων.Στη παρούσα μελέτη,εξέτασα παθοφυσιολογικές μεταβολές που έπονται της πρόκλησης ενδοεγκεγαλικούαιματώματος σε πειραματικό πρότυπο ενδοεγκεφαλικού αιματώματος σε χοίρο. Η μελέτηεπικεντρώθηκε στον προσδιορισμό των αλλαγών στον παράγοντα νέκρψσης όγκου α (TNF-α)και στην ιντερλευκίνη 1, τις πρώτες 4 και 24 ώρες από την πρόκληση του αιματώματος όπως καιστις μεταβολές των σημαντικών ενζύμων αδενοτριφωσφατασες (ATPases), σε συνδιασμό με τημελέτη της αντιοξειδωτικής αποτελεσματικότητας του Λαζαροειδούς U-74389G. Όσον αφοράτόσο τον TNF-α όσο και την IL-1, στατιστικά σημαντική αύξηση παρατηρήθηκε στο ομόπλευροτου αιματώματος ημισφαίριο στις 4 ώρες από την πρόκληση του αιματώματος και μείωση στοεικοσιτετράωρο. Ο παράγοντας U-74389G προκάλεσε στατιστικά σημαντική μείωση του TNF-αστην περιοχη του αιματώματος σε σχέση με την ομάδα ελέγχου και μείωση (αλλά όχι στατιστικάσημαντική) της IL-1 σε σύγκριση με τις ομάδες ελέγχου. Όσον αφορά στις ATPάσες, η μελέτηκατέδειξε ότι δεν προκαλείτε μείωση στη δραστικότητα της Na+,K+-ATPασης ούτε της Mg2+-ATPάσης στην περί του αιματώματος περιοχή. Η χορήγηση του U-74389G (με γνωστήνευροπροστατευτική δράση) παρουσίασε στο μοντέλο συμπεριφορά που θα μπορούσε ναθεωρηθεί νευροπροστατευτική.Στη μελέτη, εξετάστηκε επίσης ο ρόλος της ακετυλοχολινεστεράσης (AChE,σημαντικούμεμβρανικού ενζύμου που εμπλέκεται στη νευροδιαβίβαση) στο ίδιο μοντέλο, με επικέντρωσηστις πρώτες 4 και 24 ώρες από την πρόκληση του αιματώματος σε συνδιασμό με τη μελέτη τηςεπίδρασης του αντιοξειδωτικού λαζαροειδούς U- 74389G.Η μελέτη κατέδειξε την ενεργοποίησητης ακετυλοχολινεστεράσης μετά τη χορήγηση του παράγοντα U- 74389G. Το λαζαροειδές U-74389G φαίνεται να ασκεί νευροπροστατευτική δράση και αυτή είναι η πρώτη αναφορά τουρόλου του στην ενεργοποίηση του χολινεργικού συστήματος ως απάντηση στην πειραματικήπρόκληση ενδοεγκεφαλικού αιματώματο

Treatment of intracerebral hemorrhage: where do we stand?

No abstract available

Cholinergic deregulation in traumatic brain injury could be a pathophysiology-related biphasic epiphenomenon

No abstract available

The assessment of IT in the NHS A review of methods available to the NHS

SIGLEAvailable from British Library Document Supply Centre-DSC:3477.1621(406) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Neuronal tumour necrosis factor-alpha and interleukin-1beta expression in a porcine model of intracerebral haemorrhage: Modulation by U-74389G

Tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) are important mediators of intracerebral haemorrhage (ICH) inflammatory response. Lazaroids, established antioxidants and neuroprotectants, have been studied in several brain pathologies. The present study was designed to investigate: a) TNF-alpha and IL-1beta changes, in neurons and b) U-74389G effects, 4 and 24h after haematoma induction in a porcine model of intracerebral haemorrhage. In twenty male landrace pigs (swines) aged 135-150 days old, autologous whole blood was injected around the right basal ganglia territory; in ten of the pigs the lazaroid compound U-74389G was administered. Brain TNF-alpha and IL-1beta immunopositive neurons were determined by immunoarray techniques at 4 and 24h timepoints. After the haematoma induction the number of TNF-alpha immunopositive neurons ipsilateral to the haematoma was significantly higher compared to the contralateral site at 4h (p<0.0005), while U-74389G significantly reduced the number of TNF-alpha immunopositive neurons, ipsilateral to the haematoma, at 4h (p=0.002); at 24h, TNF-alpha immunopositive neurons were found significantly lower in the control group ipsilateral to the haematoma in comparison to 4h timepoint(p<0.0005). The number of IL-1beta immunopositive neurons at 4h after the hematoma induction was significantly higher ipsilateral to the haematoma site (p<0.0005). U-74389G had no statistical significant effect. TNF-alpha and IL-1beta, increase in neurons, 4h after the haematoma induction, ipsilateral to the haematoma site. The administration of the antioxidant compound U-74389G, results in early (at 4h) decrease of TNF-alpha immunopositive neurons but shows no statistical significant effect to IL-1beta immunopossitive neurons

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism

Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH

Modulation of crucial adenosinetriphosphatase activities due to U-74389G administration in a porcine model of intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) represents a partially-understood cerebrovascular disease of high incidence, morbidity and mortality. We, herein, report the findings of our study concerning the role of two important adenosinetriphosphatases (ATPases) in a porcine model of spontaneous ICH that we have recently developed (by following recent references as well as previously-established models and techniques), with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates that the examined ICH model does not cause a decrease in Na(+),K(+)-ATPase activity (the levels of which are responsible for a very large part of neuronal energy expenditure) in the perihematomal basal ganglia territory, nor a change in the activity of Mg(2+)-ATPase. This is the first report focusing on these crucial ATPases in the experimental setting of ICH and differs from the majority of the findings concerning the behavior of these (crucial for central nervous system cell survival) enzymes under stroke-related ischemic conditions. The administration of U-74389G (an established antioxidant) in this ICH model revealed an injury specific type of behavior, that could be considered as neuroprotective provided that one considers that Na(+),K(+)- and Mg(2+)-ATPase inhibition might in this case diminish the local ATP consumption

Hands train the brain-what is the role of hand tremor and anxiety in undergraduate microsurgical skills?

Introduction: Physiological hand tremor occurs naturally, due to oscillations of the upper extremities. Tremor can be exacerbated by stress and anxiety, interfering with fine motor tasks and potentially impact on surgical performance, particularly in microsurgery. We investigated the link between tremor, anxiety and performance in a neurosurgical module as part of an international surgical course. Methods: Essential Skills in the Management of Surgical Cases (ESMSC) course recruits medical students from European Union (EU) medical schools. Students are asked to suture the dura mater in an ex vivo swine model, of which the first suture completed was assessed. Questionnaires were distributed before and after the module, eliciting tremor risk factors, self-perception of tremor and anxiety. Johnson O'Connor dexterity pad was used to objectively measure dexterity. Direct Observation of Procedural Skills (DOPS) was used to assess skills-based performance. Anxiety was assessed using the Westside Test Anxiety Scale (WTAS). Tremor was evaluated by four qualified neurosurgeons. Results: Forty delegates participated in the study. Overall performance decreased with greater subjective perception of anxiety (p = 0.032, rho = -0.392). Although increasing scores for tremor at rest and overall WTAS score were associated with decreased performance, this was not statistically significant (p &gt; 0.05). Tremor at rest did not affect dexterity (p = 0.876, rho = -0.027). Conclusions: Physiological tremor did not affect student performance and microsurgical dexterity in a simulation-based environment. Self-perception of anxiety affected performance in this module, suggesting that more confident students perform better in a simulated neurosurgical setting