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Neuronal pentraxin 1: a molecular determinant of hypoxic‐ischemic brain injury
Author(s) -
Hossain Mir Ahamed
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.711.5
Subject(s) - hippocampal formation , programmed cell death , tunel assay , apoptosis , gene silencing , biology , ischemia , brain damage , neuroscience , in vivo , brain ischemia , medicine , pathology , gene , genetics
The mechanism(s) involved in neonatal hypoxic‐ischemic brain injury remain poorly understood. Here, we report the induction of a novel neuronal protein ‘neuronal pentraxin 1’ (NP1) in brain injury in neonatal animal model of hypoxia‐ischemia (HI). Neonatal brains developed marked infarcts at 24 h and showed significant loss of ipsilateral cortical and hippocampal volumes at 7 d post‐HI. Elevated expression of NP1 was observed in cortical layers and in the hippocampal CA1 and CA3 areas following HI; same brain areas that developed infarcts and increased TUNEL‐positive cells. In contrast, NP1 knockout (NP1‐KO) and NP triple KO (NP‐TKO) neonatal mice showed complete absence of brain infarction following HI compared to the wild‐type (WT) animals; supporting a role for NP1 in brain injury. Primary cortical and hippocampal neurons showed an OGD time‐dependent induction of NP1 and subsequent increase in cell death; consistent with in vivo findings. NP1 gene silencing in WT cortical neurons by NP1‐siRNA significantly reduced neuronal death, and NP1 (−/−) null cortical neurons were significantly protected against OGD. Overexpression of NP1 by infecting WT and NP1‐KO cells with pLenti6v5‐Nptx1 further enhanced the OGD‐induced neuronal death. Our findings point to a novel molecular target of brain injury, and will foster new strategies for clinical management of neonates suffering from HI. Supported by RO1NS046030.