• 2018-07
  • 2018-10
  • 2018-11
  • Recently we and others demonstrated that cells with


    Recently, we and others demonstrated that cells with astroglial characteristics and radial processes are still present in specific regions of the adult brain. These cells are termed radial glia-like cells (RGLCs) and they are present in the SVZ and in the SGL (Alvarez-Buylla et al., 2002; Gubert et al., 2009; Shapiro et al., 2005; Sundholm-Peters et al., 2004). In the SVZ, we have shown that RGLCs can be identified by their radial morphology, with the cell body in the SVZ and long processes extending to the striatum. These cells express vimentin, nestin, astrocyte-specific glutamate transporter (GLAST) and Pax6, well-known markers of radial glia cells during development (Gubert et al., 2009), and similarly to these cells, they seem to have NSC characteristics in the SVZ (Gubert et al., 2009; Mirzadeh et al., 2008). Several groups have studied the response of NSCs to injury or neurodegenerative diseases. In pathological conditions that cause neuronal death, such as cerebral ischemia, epilepsy or traumatic polycomb repressive complex injury, neurogenesis increases in the SVZ and in the SGL (Barkho and Zhao, 2011; Dash et al., 2001; Kokaia et al., 2006; Li et al., 2002; Liu et al., 1998). In these conditions, the newly formed neurons are attracted and migrate to the lesion site (Arvidsson et al., 2002; Jin et al., 2003; Kokaia et al., 2006; Parent et al., 2002; Zhang et al., 2001). After an injury that affects glial cells such as oligodendrocytes, a similar response is observed; NSC proliferation increases and newly formed oligodendrocyte progenitors migrate to the lesion (Gonzalez-Perez and Alvarez-Buylla, 2011; Menn et al., 2006; Picard-Riera et al., 2002). However, even though the endogenous NSCs respond to injuries, this increase in proliferation is insufficient to replace a significant number of the lost cells. In an attempt to regenerate or protect neural cells after injury, several research groups are testing therapies with stem cells in animal models and humans (Barbosa da Fonseca et al., 2009, 2010; Friedrich et al., 2012; Pimentel-Coelho and Mendez-Otero, 2010; Rost et al., 2012; Thwaites et al., 2012). One of the sources of stem cells used is bone marrow, and several studies using animal models of neurological diseases have shown that these cells can attenuate the functional loss after an injury to the nervous system (de Vasconcelos Dos Santos et al., 2010; Giraldi-Guimaraes et al., 2012; Li et al., 2006; Ribeiro-Resende et al., 2009; Vasconcelos-Dos-Santos et al., 2012; Zaverucha-do-Valle et al., 2011). Although the mechanisms involved in the therapeutic effects described above are still subject to debate, it is accepted that these cells migrate to the lesion area and probably release neuroprotective and/or trophic factors that may have neuroprotective and/or neuroregenerative functions. In this respect, several studies have demonstrated that bone-marrow therapy reduces cell death, glial scar formation, microglial activation and inflammation, protects the tissue against insult, and also stimulates axonal growth (Costa-Ferro et al., 2012; de Vasconcelos Dos Santos et al., 2010; Li et al., 2005; Ohtaki et al., 2008; Ribeiro-Resende et al., 2009; Schwarting et al., 2008; Zaverucha-do-Valle et al., 2011). It has also been demonstrated that bone-marrow therapy increases the proliferation of NSCs in the SVZ and SGL (Chen et al., 2003; Kan et al., 2011), and some growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) or fibroblast growth factor-2 (FGF-2) have been found to be related to this event (Cao et al., 2004; Craig et al., 1996; Doetsch et al., 2002; Sun et al., 2009). In addition, infusion of growth factors could also increase the number of RGLCs in the SVZ of adult mice (Gregg and Weiss, 2003). In the present study, we subjected adult rats to chronic cerebral hypoperfusion, a model of global cerebral ischemia that decreases the cerebral blood flow to about 25 to 94% of the normal levels (Tsuchiya et al., 1992) and causes damage mainly in the white matter (Kurumatani et al., 1998; Wakita et al., 2002). We investigated if in this model of moderate brain injury, intravenously injected bone-marrow cells migrate to the brain and have any effect on the SVZ, an important NSC niche in the adult brain.