Adulte Neurogenese im Gyrus dentatus der Ratte 28 Tage nach inkompletter globaler zerebraler Ischämie und Reperfusion und deren Beeinflussung durch S(+)Ketamin

Kaeppel, Birgit (2005): Adulte Neurogenese im Gyrus dentatus der Ratte 28 Tage nach inkompletter globaler zerebraler Ischämie und Reperfusion und deren Beeinflussung durch S(+)Ketamin. Dissertation, LMU München: Tierärztliche Fakultät

Abstract

The effect of S(+)ketamine on neuroregenerative potency in the dentate gyrus of the adult rat after incomplete global cerebral ischemia and reperfusion The present study investigates the concentration dependent effect of the anaesthetic agent S(+)ketamine on the neuronal damage in the hippocampus and on the adult neurogenesis in the rat after incomplete global cerebral ischemia and reperfusion after a time period of 28 days. Animals were randomly assigned to one of the following anaesthetic groups: halothane (0.8 Vol%), S(+)ketamine 0.75 mg/kg/min and S(+)ketamine 1.0 mg/kg/min. Each anaesthetic group was subdivided into an ischemic group and a control group (each group n=8). Ischemia of the forebrain was induced by bilateral occlusion of the common carotid arteries for 10 minutes in combination with hemorrhagic hypotension (mean arterial pressure: 40 mmHg) in animals of the three ischemic but not in the three control groups. A native group (n = 8) without any treatment serves as physiological control for the histological examinations in addition to the operated test groups. To mark the stem cells in vivo 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg) was injected intraperitoneally to all animals. After 28 days at the end of the observation period the animals were euthanized and the brains were prepared for further analysis. We used a Hematoxylin-Eosin (HE) staining to evaluate the extent of tissue damage in the CA1- and CA3-region of the hippocampus. The immunohistochemical detection of BrdU, which was incorporated into the nucleus of mitotic cells, was performed to examine the number of proliferating cells in the dentate gyrus. To differentiate whether newly formed cells were neurons or other cells, an additional double immunofluorescence staining with BrdU and the neuronal marker NeuN was performed and the ratio of neurogenesis assessed. HE-staining revealed no significant differences in the extent of the ischemic damage dependant of the mode of anaesthesia, although there was a tendency found that S(+)ketamine in a dosage of 1.0 mg/kg/min seems to reduce the neuronal damage compared to halothane anaesthesia. The results of the BrdU-staining show an increase of cell proliferation after an ischemic insult compared with the control groups and the native group. But neither in the control groups nor in the ischemic groups were significant differences in the number of BrdU-positive cells dependent of the chosen anaesthetic agents or dosages. There was a trend of S(+)ketamine in higher dosages to reduce the neuroregenerative potency. The data of the double immunofluorescence staining showed that neither the mode of anaesthesia nor the induction of an ischemic insult influenced the differentiation of newly born cells. In summary, the findings suggest that a high dose of S(+)ketamine acts neuroprotective up to 28 days after an ischemic insult, but concurrently reduces the extent of damage-induced neurogenesis. Further investigations will be required to investigate the detailed mechanisms of the anestheic agent S(+)ketamine on neuroregenerative potency and to develop a successful treatment of ischemic insult and its consequences.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 590 Tiere (Zoologie)
• Fakultäten: Tierärztliche Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 15. Juli 2005
• 1. Bericht­erstatter:in: Schmahl, Wolfgang