Sophorn Chip

Publications (2)10.86 Total impact

• Article: Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death.

  Sophorn Chip, Cordula Nitsch, Sven Wellmann, Josef P Kapfhammer
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  ABSTRACT: Transient ischemia causes delayed neurodegeneration in selective brain areas, particularly in the CA1 field of the hippocampus. This is accompanied by neurovascular impairment. It is unknown whether neurodegeneration is the cause or consequence of vascular changes. In an entorhino-hippocampal-organotypic slice culture system with well-preserved blood vessels, we studied the interplay between neurodegeneration and neurovasculature. Short-term oxygen and glucose deprivation (OGD) resulted in upregulation of hypoxic markers and with a delay of 24 to 48 hours in selective nerve cell death in CA1. In parallel, local vessel density decreased as detected by markers of endothelial cells and of the extracellular matrix. Claudin-5, a tight junction protein and marker of the blood-brain barrier was reduced. Preventing neuronal death with tetrodotoxin or 6-cyano-7-nitroquinoxaline-2,3-dione rescued blood vessels, suggesting that vessel loss is not due to OGD per se but a consequence of neuronal death. Induction of excitotoxic neuronal death with AMPA caused widespread neurodegeneration, but vessel reduction was confined to CA1. In dentate gyrus without neuronal loss, vessel density increased. We propose that neuronal stress and death influence maintenance, loss and remodeling of the neurovasculature and that the type of vascular response is in addition determined by local factors within the hippocampus.Journal of Cerebral Blood Flow & Metabolism advance online publication, 12 December 2012; doi:10.1038/jcbfm.2012.190.
  Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 12/2012; · 5.46 Impact Factor
• Article: The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection.

  Sophorn Chip, Andrea Zelmer, Omolara O Ogunshola, Ursula Felderhoff-Mueser, Cordula Nitsch, Christoph Bührer, Sven Wellmann
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  ABSTRACT: Induced hypothermia is the only therapy with proven efficacy to reduce brain damage after perinatal asphyxia. While hypothermia down-regulates global protein synthesis and cell metabolism, low temperature induces a small subset of proteins that includes the RNA-binding protein RBM3 (RNA-binding motif protein 3), which has recently been implicated in cell survival. Here, immunohistochemistry of the developing postnatal murine brain revealed a spatio-temporal neuronal RBM3 expression pattern very similar to that of doublecortin, a marker of neuronal precursor cells. Mild hypothermia (32°C) profoundly promoted RBM3 expression and rescued neuronal cells from forced apoptosis as studied in primary neurons, PC12 cells, and cortical organotypic slice cultures. Blocking RBM3 expression in neuronal cells by specific siRNAs significantly diminished the neuroprotective effect of hypothermia while vector-driven RBM3 over-expression reduced cleavage of PARP, prevented internucleosomal DNA fragmentation, and LDH release also in the absence of hypothermia. Together, neuronal RBM3 up-regulation in response to hypothermia apparently accounts for a substantial proportion of hypothermia-induced neuroprotection.
  Neurobiology of Disease 08/2011; 43(2):388-96. · 5.40 Impact Factor