Clinical Neuroscience

[OPTIMAL ALIGNMENT®. NOVEL SOFTWARE PROCEDURE FOR 3D RECONSTRUCTION OF ELECTRONMICROSCOPIC SERIAL SECTIONS]

SIMON László, GARAB Sándor, NOSZEK Annamária, ELIZABETH Römmer, ZÁBORSZKY László

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

[3D reconstruction from electronmicroscopic (EM) serial sections substantially differs from modeling body parts by linking convoluted planes delivered by CT and NMR. Namely, variations both in relative X-Y position and rotation of the target elements between the adjacent images and also additional problems caused by deformed, deteriorated or missing sections can only be overruled by an aligning paradigm, which exploits all the pixel-level information, and results in an optimal fitting with selected precision. This paper presents a complex computer program called Optimal Alignment®, which performs the precise elaboration of X-Y shift and relative rotation of two consecutive images. The required searching process will be customized by setting four independent parameters which relate the span and density of the pixel-scanning basic process. Optimalization of fitting accuracy versus running time can be achieved by a rather short training period. The potential precision of Optimal Alignment based on complex algorythms is far superior to manual aligning of EM photographs with the eye-wrist-mouse facility. The resulted database of alignment orientation parameters can serve as an advanced source for the 3D reconstructing programs. Optimal Alignment® software tool (supported by Hungarian Space Office grant TP 138) will be demonstrated on a basal forebrain NPY+ axonal reconstruction, performed in L. Záborszky’s laboratory (supported by NIH grant NSO23945).]

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Clinical Neuroscience

[PROTECTIVE ACTION OF SNAKE VENOM NAJA NAJA OXIANA AT SPINAL CORD HEMISECTION]

ABRAHAMYAN S. Silva, MELIKSETYAN B. Irina, CHAVUSHYAN A. Vergine, ALOYAN L. Mery, SARKISSIAN S. John

[Based on data accumulated regarding the neuroprotective action of Proline-Rich-Peptide-1 (PRP-1, a fragment of neurophysin vasopressin associated hypothalamic glycoprotein consisting of 15 amino acid residues) on neurons survival and axons regeneration and taking into the account that LVV-Hemorphin-7 (LVV-H7, an opioid peptide, widely distributed in different cell types of various tissues of intact rats, including those of the nervous and immune systems) derived from the proteolitic processing of hemoglobin in response to adverse environmental and physiological conditions, possesses the anti-stressor properties, we used histochemistry, immunohistochemistry and electrophysiology to investigate the putative neuroprotective action of Central Asian Cobra Naja naja oxiana snake venom (NOX) on trauma-injured rats. ABC immunohistochemical method and histochemical method on detection of Ca2+- dependent acid phosphatase activity were used for the morpho-functional study. By recording the electrical activity of the signals from the single neurons in and below the SC injury place, NOX venom has been shown to result in the complete restoration of hypothalamic-spinal projections originated from ipsi- and contra-lateral PVN and SON to neurons of SC lumbar part. NOX prevented the scar formation, well observed two months after SC injury in the control rats, resulted in the regeneration of nerve fibers growing through the trauma region, survival of the PRP-1- and LVV-H7-immunoreactive (Ir) neurons, and increase of the PRP-1- and LVV-H7-Ir nerve fibers and astrocytes in the SC lesion region. NOX was suggested to exert the neuroprotective effect, involving the PRP-1 and LVV-H7 in the underlying mechanism of neuronal recovery.]

Clinical Neuroscience

[CENTRAL ATRIAL NATRIURETIC PEPTIDE IN DEHYDRATION]

BAHNER Udo, GEIGER Helmut, PALKOVITS Miklós, LENKEI Zsolt, LUFT C. Friedrich, HEIDLAND August

[To test the effect of dehydration on brain atrial natriuretic peptide (ANP) concentrations in areas important to salt appetite, water balance and cardiovascular regulation, we subjected rats to dehydration and rehydration and measured ANP concentration in 18 brain areas, as well as all relevant peripheral parameters. Water deprivation decreased body weight, blood pressure, urine volume, and plasma ANP, while it increased urine and plasma osmolality, angiotensin II, and vasopressin. ANP greatly increased in 17 and 18 brain areas (all cut cerebral cortex) by 24 h. Rehydration for 12 h corrected all changes evoked by dehydration, including elevated ANP levels in brain. We conclude that chronic dehydration results in increased ANP in brain areas important to salt appetite and water balance. These results support a role for ANP as a neuroregulatory substance that participates in salt and water balance.]

Clinical Neuroscience

[OXYGEN-GLUCOSE DEPRIVATION-INDUCED CHANGES IN ORGANOTYPIC CULTURES OF THE RAT HIPPOCAMPUS]

BALI Balázs, NAGY Zoltán, KOVÁCS J. Krisztina

[Introduction - (-)Deprenyl is an irreversible inhibitor of type B monoamine oxidase (MAO-B), which is now used for treatment of Parkinson’s or Alzheimer’s diseases. Evidence suggests that the neuroprotective effect of deprenyl may not be related exclusively to the inhibition of the enzyme MAO-B. Methods - To test the impact of deprenyl on ischemiainduced changes in vitro, we followed the time course of propidium iodide (PI) uptake as an indicator of neuronal cell death as well as the expression of apoptotic factors in organotypic hippocampal slice cultures exposed to oxygen- glucose deprivation (OGD) for 45 min. Results - The first signs of neuronal death were detected 2 hours after OGD and were extended to all subfields of the hippocampus by 24 hours post-injury. Presence of deprenyl (10-9 M) significantly delayed the cell death induced by the insult. Exposure of control cultures to deprenyl significantly increased the abundance of Bcl-2 and Bcl-xl mRNAs as revealed by RT-PCR. OGD resulted in an elevation of anti-apoptotic factors, while the expression of pro-apoptotic bax remained unchanged. Conclusion - These data suggest that deprenyl is neuroprotective in an in vitro model of ischemia. Although deprenyl upregulates the expression of Bcl-2 under basal conditions, its effect on anti-apoptotic factors is not significantly manifested during OGD.]

Clinical Neuroscience

[EFFECT OF LOCAL (INTRACEREBRAL AND INTRACEREBROVENTRICULAR) ADMINISTRATION OF TYROSINE HYDROXYLASE INHIBITOR ON THE NEUROENDOCRINE DOPAMINERGIC NEURONS AND PROLACTIN RELEASE]

BODNÁR Ibolya, HECHTL Dániel, SZÉKÁCS Dániel, OLÁH Márk, NAGY M. György

[Background and purpose - Hypothalamic dopamine (DA), the physiological regulator of pituitary prolactin (PRL) secretion, is synthesized in the neuroendocrine DAergic neurons that projects to the median eminence and the neurointermediate lobe of the pituitary gland. The rate-limiting step of DA biosynthesis is catalyzed by the phosphorylated, therefore activated, tyrosine hydroxylase (TH) that produces L-3,4-dihydroxy- phenylalanine from tyrosine. The aims of our present study were to investigate 1. the effect of local inhibition of the DA biosynthesis in the hypothalamic arcuate nucleus on PRL release, and to get 2. some information whether the phosphorylated TH is the target of enzyme inhibition or not. Methods - A TH inhibitor, α-methyl-p-tyrosine was injected either intracerebro-ventricularly or into the arcuate nucleus of freely moving rats and plasma PRL concentration was measured. Immunohistochemistry, using antibodies raised against to native as well as phosphorylated TH were used to compare their distributions in the arcuate nucleus-median eminence region. Results - Intracerebro-ventricular administration of α-methyl-p-tyrosine has no effect, unlike the intra-arcuatus injection of enzyme inhibitor resulted in a slight but significant elevation in plasma PRL. Parallel with this, the level of DA and DOPAC were reduced in the neurointermediate lobe while no change in norepinephrine concentration can be detected indicating a reduced biosynthesis of dopamine following TH inhibition. On the other hand, systematic application of the α-methyl-p-tyrosine that inhibits TH activity located in DA terminals of the median eminence and the neurointermediate lobe, resulted in the most significant elevation of PRL. Conclusion - Our results suggest that α-methyl-p-tyrosine administered close to the neuroendocrine DAergic neurons was able to inhibit only a small proportion of the TH. Moreover, it also indicate that the majority of the activated TH can be found in the axon terminals of DAergic neurons, therefore, the DA released into the pituitary portal circulation is synthesized at this site.]

Clinical Neuroscience

[USING BRAIN SLICE CULTURES OF MOUSE BRAIN TO ASSESS THE EFFECT OF GROWTH FACTORS ON DIFFERENTIATION OF BONE MARROW DERIVED STEM CELLS]

BRATINCSÁK András, LONYAI Anna, SHAHAR Tal, HANSEN Arne, TÓTH E. Zsuzsanna, MEZEY Éva

[Bone marrow derived stem cells (BMDSCs) have been reported to form neurons and supportive cells in the brain. We describe a technique that combines the simplicity of in vitro studies with many of the advantages of in vivo experiments. We cultured mouse brain slices, deposited GFPtagged BMDSCs evenly distributed on their surfaces, and then added test factors to the culture medium. Addition of both SDF-1 and EGF resulted in morphological changes of BMDSC and in the induction of islet-1, a marker of neuroepithelial progenitors. We conclude that organotypic tissue culture (OTC) may allow us to detect the effects of exogenous factors on the differentiation of BMDSCs (or any other type of stem cells) in an environment that may resemble the CNS after brain injury. Once such factors have been identified they could be evaluated for tissue regeneration in more complex, whole animal models.]

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[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]

JANSZKY József, HORVÁTH Réka, KOMOLY Sámuel

[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]

Clinical Neuroscience

[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]

RAJNA Péter

[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

LAM KID

[New findings in the cortical bone biology and its role in bone fractures]

BALOGH Ádám, BHATTOA Harjit Pál

[The authors surveyed the already known factors responsible for the osteoporotic bone fragility. Then the results of using modern imaging techniques (micro-CT, high-resolution peripheral computed quantitative tomograph - HR-pQCT) and advanced computer analytic methods (finite element analysis, FEA) are presented. These data - beyond the already known fracture risk factors (age, risk of falling, bone mineral density - BMD, and fine structure damage of trabecular bone) are stressing the importance of the (micro)damage of cortical bone as a fracture risk factor, which has been still underrated. The cortical thickening and increased porosity - verified on various population samples - are increasing the risk of fractures in certain subgroups of subjects having identical BMD values, even among those, who are considered only osteopenic by the earlier classification based on BMD values. Backed with modern software batteries, the new imaging techniques are expected to enter clinical application in the near future. Pharmacologic agents with stronger cortical effect are already available and research is continuing to find new drugs to use in the management of osteoporotic patients of high fracture risk.]

Clinical Neuroscience

[Earlier and more efficiently: the role of deep brain stimulation for parkinson’s disease preserving the working capabilities]

DELI Gabriella, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ASCHERMANN Zsuzsanna, NAGY Ferenc, BOSNYÁK Edit, KOVÁCS Norbert

[Background – The recently published “EarlyStim” study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. Methods – We reviewed the data of 39 young (<60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job (“Job+” group, n=15) and retired patients (without active job, “Job-” group, n=24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. Results – As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p<0.01, McNemar test). Conclusion – Although our retrospective study has several limitations, our results fit well with the conclusions of “EarlyStim” study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.]

Lege Artis Medicinae

[Notes on the management of hypertension in chronic kidney disease ]

AMBRUS Csaba

[The prevalence of hypertension among pa­tients with chronic kidney disease is high, reaching more than 80%. Hypertension is both one of the main causes and also the most common consequence of chronic kidney disease. It is also a main factor responsible for the high cardiovascular morbidity and mortality in this patient population. Blood pressure control can improve patient outcomes, lower cardiovascular risk and slow down the progression of kidney dis­ease, irrespective of the underlying cause. The optimal therapy should therefore focus not only on blood pressure reduction but also on renoprotection. Basic understanding of the renal pathophysiology in hypertension and renal effects of various medications is of paramount importance. In this review, we summarized cornerstones of the antihypertensive therapy in patients with chronic kidney disease. The management of patients receiving kidney replacement therapies, such as hemodialysis, peritoneal dialysis or transplanta­tion requires special knowledge and expe­rience, therefore it is not discussed here. The aim of this review was to allow non-nephrologist physicians to take care of their kidney patients with more confidence and effectiveness.]