Institute of Interdisciplinary Isotope Research

Leipzig, Germany

Institute of Interdisciplinary Isotope Research

Leipzig, Germany
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Donat C.K.,Institute of Interdisciplinary Isotope Research | Walter B.,Friedrich - Schiller University of Jena | Kayser T.,Institute of Interdisciplinary Isotope Research | Deuther-Conrad W.,Institute of Interdisciplinary Isotope Research | And 5 more authors.
International Journal of Developmental Neuroscience | Year: 2010

Traumatic brain injury is a leading cause of death and disability in children. Studies using adult animal models showed alterations of the central cholinergic neurotransmission as a result of trauma. However, there is a lack of knowledge about consequences of brain trauma on cholinergic function in the immature brain. It is hypothesized that trauma affects the relative acetylcholine esterase activity and causes a loss of cholinergic neurons in the immature brain. Severe fluid percussion trauma (FP-TBI, 3.8 ± 0.3 atm) was induced in 15 female newborn piglets, monitored for 6 h and compared with 12 control animals. The hemispheres ipsilateral to FP-TBI obtained from seven piglets were used for acetylcholine esterase histochemistry on frozen sagittal slices, while regional cerebral blood flow and oxygen availability was determined in the remaining eight FP-TBI animals. Post-fixed slices were immunohistochemically labelled for choline acetyltransferase as well as for low-affinity neurotrophin receptor in order to characterize cholinergic neurons in the basal forebrain. Regional cerebral blood flow and brain oxygen availability were reduced during the first 2 h after FP-TBI (P < 0.05). In addition, acetylcholine esterase activity was significantly increased in the neocortex, basal forebrain, hypothalamus and medulla after trauma (P < 0.05), whereas the number of choline acetyltransferase and low-affinity neurotrophin receptor positive cells in the basal forebrain were unaffected by the injury. Thus, traumatic brain injury evoked an increased relative activity of the acetylcholine esterase in the immature brain early after injury, without loss of cholinergic neurons in the basal forebrain. These changes may contribute to developmental impairments after immature traumatic brain injury. © 2009 ISDN.


Donat C.K.,Institute of Interdisciplinary Isotope Research | Walter B.,Friedrich - Schiller University of Jena | Deuther-Conrad W.,Institute of Interdisciplinary Isotope Research | Wenzel B.,Institute of Interdisciplinary Isotope Research | And 3 more authors.
Neuropathology and Applied Neurobiology | Year: 2010

Aims: Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. Adult animal models of TBI showed cholinergic alterations. However, there is no comparable data on immature animals. Therefore, this study investigates cholinergic markers in a large animal model of juvenile TBI. Methods: Twenty-seven female newborn piglets were subjected to lateral fluid percussion (FP) injury and compared with 12 untreated animals. After 6 h, animals were sacrificed and the brains removed. The hemispheres ipsilateral to FP-TBI from seven piglets and corresponding hemispheres from six control animals were used for autoradiography. Receptor density was determined with [3H]epibatidine (nicotinic acetylcholine receptors) or [ 3H]QNB (muscarinic acetylcholine receptors). The density of the vesicular acetylcholine transporter (vAChT) was assessed with (-)-[ 3H]vesamicol. Cerebral blood flow was measured by coloured microsphere method. Results: Cerebral blood flow and brain oxygen delivery were transiently reduced early after FP-TBI (P < 0.05). TBI caused reductions of muscarinic acetylcholine receptor density (fmol/mg) in the basal forebrain (sham: 10797 ± 1339, TBI: 8791 ± 1031), while nicotinic acetylcholine receptor remained stable. Significant increases in vAChT density (fmol/mg) were observed in the basal forebrain (sham: 2347 ± 171, TBI: 2884 ± 544), putamen (sham: 2276 ± 181, TBI: 2961 ± 386), cortex (sham: 1928 ± 262, TBI: 2377 ± 294), thalamic areas (sham: 2133 ± 272, TBI: 2659 ± 413), hippocampus (sham: 2712 ± 145, TBI: 3391 ± 501) and hypothalamus (sham: 2659 ± 139, TBI: 3084 ± 304). Conclusions: Cholinergic markers are altered after mild-to-moderate TBI in the immature brain. Whereas the ACh receptors are stable in almost any brain region after TBI, vAChT expression increases after trauma at the employed severity of this specific trauma model. © 2010 Blackwell Publishing Ltd.


Chandra Sekhar K.V.G.,Birla Institute of Technology and Science | Rao V.S.,Birla Institute of Technology and Science | Deuther-Conrad W.,Institute of Interdisciplinary Isotope Research | Sridhar D.,Birla Institute of Technology and Science | And 4 more authors.
Medicinal Chemistry Research | Year: 2013

A series of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl] phenyl} thiazoles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were designed, synthesized, and characterized by spectral data (IR, 1H NMR, and MS) and the purity was ascertained by microanalysis. The D2 and 5-HT2A affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized final compounds (10a-g; 11a-g; 12a-g) were screened for their in vivo pharmacological activity in Swiss albino mice. D2 antagonism studies were performed using climbing mouse assay model and 5-HT2A antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 12d, 11f, and 10a were found to be the most active compounds with 5-HT2A/D2 ratio of 1.23077, 1.14286, and 1.12857, respectively, while the standard drug risperidone exhibited 5-HT2A/D2 ratio of 1.0989. Among the twenty one new chemical entities, three compounds (12d, 11f, and 10a) were found to exhibit better atypical antipsychotic activity as they were found to have higher Meltzer index than the standard drug risperidone. © 2012 Springer Science+Business Media, LLC.


Franke K.,Institute of Interdisciplinary Isotope Research | Kupsch H.,Institute of Interdisciplinary Isotope Research
Radiochimica Acta | Year: 2010

The known IODO-GEN-method [1] was adapted for radiolabeling of humic and fulvic acids with 131I. The water insoluble oxidizing agent l,3,4,6tetraehloro-3α,6α-diphenylglyeoluril (IODO-GEN ™) forms an iodous ion species (I+), which undergoes an eleetrophilic I/H-substitution on aromatic moieties of the humic and fulvic acids. This method offers mild conditions with a lesser extent of oxidative alterations of the target molecule, accompanied by an easy handling due to the virtual water-insolubility of the oxidizing agent. The method was optimized and different techniques were tested for the purification of the radioiodinated humic material. The yield of the labeling procedure varies between 45 and 75% depending on the provenance of the humic material and the applied purification method. A specific activity up to 40MBq/mg was achieved. Furthermore, the known inherent photo-susceptibility of the iodinated humic substance and the influence of reducing agents were verified. An additional release of 131I up to 20% and up to 35%, respectively were observed. © Oldenbourg Wissenschaftsverlag, München.


PubMed | Institute of Interdisciplinary Isotope Research
Type: Journal Article | Journal: Neuropathology and applied neurobiology | Year: 2010

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. Adult animal models of TBI showed cholinergic alterations. However, there is no comparable data on immature animals. Therefore, this study investigates cholinergic markers in a large animal model of juvenile TBI.Twenty-seven female newborn piglets were subjected to lateral fluid percussion (FP) injury and compared with 12 untreated animals. After 6 h, animals were sacrificed and the brains removed. The hemispheres ipsilateral to FP-TBI from seven piglets and corresponding hemispheres from six control animals were used for autoradiography. Receptor density was determined with [(3)H]epibatidine (nicotinic acetylcholine receptors) or [(3)H]QNB (muscarinic acetylcholine receptors). The density of the vesicular acetylcholine transporter (vAChT) was assessed with (-)-[(3)H]vesamicol. Cerebral blood flow was measured by coloured microsphere method.Cerebral blood flow and brain oxygen delivery were transiently reduced early after FP-TBI (P < 0.05). TBI caused reductions of muscarinic acetylcholine receptor density (fmol/mg) in the basal forebrain (sham: 10797 +/- 1339, TBI: 8791 +/- 1031), while nicotinic acetylcholine receptor remained stable. Significant increases in vAChT density (fmol/mg) were observed in the basal forebrain (sham: 2347 +/- 171, TBI: 2884 +/- 544), putamen (sham: 2276 +/- 181, TBI: 2961 +/- 386), cortex (sham: 1928 +/- 262, TBI: 2377 +/- 294), thalamic areas (sham: 2133 +/- 272, TBI: 2659 +/- 413), hippocampus (sham: 2712 +/- 145, TBI: 3391 +/- 501) and hypothalamus (sham: 2659 +/- 139, TBI: 3084 +/- 304).Cholinergic markers are altered after mild-to-moderate TBI in the immature brain. Whereas the ACh receptors are stable in almost any brain region after TBI, vAChT expression increases after trauma at the employed severity of this specific trauma model.

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