Abstract
Adult neurogenesis is present in the dentate gyrus and the subventricular zone in mammalian brain under physiological conditions. Recently, adult neurogenesis has also been reported in other brain regions after brain injury. In this study, we established a focal striatal ischemic model in adult mice via photothrombosis (PT) and investigated how focal ischemia elicits neurogenesis in the striatum. We found that astrocytes and microglia increased in early post-ischemic stage, followed by a 1-week late-onset of doublecortin (DCX) expression in the striatum. The number of DCX-positive neurons reached the peak level at day 7, but they were still observed at day 28 post-ischemia. Moreover, Rbp-J (a key effector of Notch signaling) deletion in astrocytes has been reported to promote the neuron regeneration after brain ischemia, and we provided the change of gene expression profile in the striatum of astrocyte-specific Rbp-J knockout (KO) mice glial fibrillary acidic protein (GFAP-CreER:Rbp-Jfl/fl), which may help to clarify detailed potential mechanisms for the post-ischemic neurogenesis in the striatum.
Highlights
Ischemic brain stroke is a serious disease with high incidence and poor prognosis worldwide if systemic thrombolysis or endovascular treatment is not applied in time, and it may result in memory disorder, vascular dementia, affective disorder and ataxia (Donnan et al, 2008; Khandelwal et al, 2016)
Because the deletion of Rbp-J, a key component of Notch signaling, has been reported to promote neural regeneration in middle cerebral artery occlusion (MCAO)-induced ischemia (Magnusson et al, 2014), we investigated the changes of the transcription factors in the striatum of astrocyte-specific Rbp-J knockout (KO) mice in order to provide more insight into this process
Nissl staining showed an obvious loss of cellular structure in the ischemic region at day 2, and 5, but it became smaller at day 7 and 14 and was repopulated with Nissl-stained cells at day 28 after the focal ischemia, most of which were Glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium binding adapter molecule 1 (Iba1)-positive microglia (Figures 1C,E)
Summary
Ischemic brain stroke is a serious disease with high incidence and poor prognosis worldwide if systemic thrombolysis or endovascular treatment is not applied in time, and it may result in memory disorder, vascular dementia, affective disorder and ataxia (Donnan et al, 2008; Khandelwal et al, 2016). It is well accepted that active adult neurogenesis is present in the mammalian brain it is largely restricted to the dentate gyrus and the subventricular zone lining the lateral ventricle (Duan et al, 2008; Zhao et al, 2008; Ming and Song, 2011). The current methods to build ischemic animal models in adult mammalian brain include the middle cerebral artery occlusion (MCAO; Memezawa et al, 1992), electric coagulation and photothrombosis (PT). The infarct area induced by MCAO often covers one third or even larger brain regions in transverse sections, and this large damage is not often present in survived patients. PT shows great strengths in building striatal ischemic models (Kuroiwa et al, 2009)
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