Einfluss von Minocyclin und Indometacin auf trainingsinduzierte Neurogenese nach experimentellen Schlaganfällen

Schlegel, Nadja GND

Rehabilitative training has been shown to stimulate neurogenesis in the dentate gyrus following stroke and supports hippocampal function. Increasing evidence also indicates that ischemic insults impair neurogenic plasticity. Since inflammatory processes are possibly involved in stroke-induced disturbance of dentate neurogenesis we analyzed whether treatment with anti-inflammatory drugs further promotes training-induced dentate neurogenesis and hippocampal function. Using the photothrombosis model, cortical infarcts were induced in the forelimb and hindlimb sensorimotor cortex of adult rats. After the infarct three groups of animals received daily skilled training of the impaired forepaw and intraperitoneal application of minocycline, indometacin or vehicle during the first two weeks. Another group of control animals received vehicle injections without daily reaching training. Whilst proliferating progenitors were labeled by bromodeoxyuridine injections between day 2-6 post-infarct, dentate neurogenesis was immunocytochemically analyzed 42 days after lesion. Using this approach, we clearly demonstrate that both drugs strongly enhance the effects of skilled reaching training on adult neurogenesis in the dentate gyrus. Compared to animals receiving reaching training alone we detected approximately 60 % more newborn neurons. Assessed against controls with neither training nor drug treatment, post-lesional dentate neurogenesis was more than doubled. Behavioral testing in the Morris water maze from day 35 to day 42 revealed that this increased levels of dentate neurogenesis have marginal effects on spatial learning performance. Combined rehabilitative training and administration of the anti-inflammatory agents minocycline or indometacin significantly promote neurogenesis in the dentate gyrus following stroke, but increased dentate neurogenesis in the context of stroke is not necessarily associated with improved hippocampal performance.


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Schlegel, Nadja: Einfluss von Minocyclin und Indometacin auf trainingsinduzierte Neurogenese nach experimentellen Schlaganfällen. 2014.

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