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The Pro-Apoptotic Substance Thapsigargin Selectively Stimulates Re-Growth of Brain Capillaries

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Thapsigargin is a pro-apoptotic chemical, which has been shown to be useful to study cell death of cholinergic or dopaminergic neurons, or cells, which degenerate in Alzheimer's disease or Parkinson's disease, respectively. The aim of the present work was to study the effects of thapsigargin in the well established organotypic brain co-slice model composed of the basal nucleus of Meynert (nBM), ventral mesencephalon (vMes), dorsal striatum (dStr) and parietal cortex (Ctx). Cholinergic acetyltransferase-positive neurons in the nBM and dStr and dopaminergic tyrosine hydroxylasepositive neurons in the vMes survived, when cultured for 4 weeks with nerve growth factor and glial cell line-derived neurotrophic factor. Nerve fibers of cholinergic nBM neurons grew into the cortex and dopaminergic nerve fibers sprouted into dopamine D2 receptor-positive dStr. The whole co-slice contained a dense laminin-positive capillary network. Treatment of co-cultures with 3 μM thapsigargin for 24 hr significantly decreased the number of cholinergic neurons and dopaminergic neurons. This cell death displayed apoptotic DAPI-positive malformed nuclei and enhanced TUNEL-positive cells. Thapsigargin selectively stimulated the laminin-positive capillary growth between the nBM and Ctx. In conclusion, the induced cell death of cholinergic and dopaminergic neurons may be accompanied by enhanced angiogenic activity.

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Keywords: Angiogenesis; in vitro model; neuronal cell death; vascularization

Document Type: Research Article

Publication date: 2009-08-01

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  • Current Neurovascular Research (CNR) provides a cross platform for the publication of scientifically rigorous research that addresses disease mechanisms of both neuronal and vascular origins in neuroscience. The journal serves as an international forum for the publication of novel and pioneering original work as well as timely neuroscience research reviews in the disciplines of cell developmental disorders, plasticity, and degeneration that bridge the gap between basic science research and clinical discovery. CNR emphasizes the elucidation of disease mechanisms, both cellular and molecular, which can impact the development of unique therapeutic strategies for neuronal and vascular disorders.
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