Neural progenitor cells NPCs are self renewing multipotent c

Neural progenitor cells (NPCs) are self-renewing, multipotent cells that are capable of differentiating into neurons, astrocytes and oligodendrocytes. NPCs are activated in response to a variety of pathological states in neurodegenerative diseases such as Parkinson’s disease and multiple sclerosis, as well as in cytochalasin d injuries such as ischemia, trauma and epilepsy (Mazurova et al., 2006). Cell death is a characteristic of acute CNS disorders and neurodegenerative diseases. The loss of cells is amplified by the lack of regenerative abilities for cell replacement and repair in the CNS. One way to circumvent this is to use cell replacement therapy via regenerative NPCs. These NPCs proliferated with growth factors such as EGF and bFGF in vitro. Upon withdrawal of these growth factors, NPCs differentiate into neurons, astrocytes, or oligodendrocytes which can be transplanted within the brain at the site of injury (Bonnamain et al., 2012, Kim et al., 2008, Xu et al., 2011). The benefits of this therapeutic approach have been examined inParkinson’s disease (Richardson et al., 2005),Huntington's disease (McBride et al., 2004), andmultiple sclerosis (Cohen et al., 2014, Donegà et al., 2014). Transplanted NPCs can integrate within existing host circuitry, provide and provoke trophic support, and modulate host immune responses. Importantly, NPC-mediated trophic secretion can mobilize endogenous stem cells and enhance neurodegenerative responses, within the injured milieu (Cossetti et al., 2012, Shetty, 2014). A recent study showed that transplantation of NPCs may be a potential treatment strategy for traumatic brain injury (TBI) due to their intrinsic advantages, including the secretion of neurotrophins (Blaya et al., 2015). NPCs displayed processes that extended into several remote structures, including the hippocampus and contralateral cortex. NPCs conferred significant preservation of pericontusional host tissues and enhanced hippocampal neurogenesis (Blaya et al., 2015). On the other hand, transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord (Cusimano et al., 2012). It had reported that systemic transplantation of NPCs ameliorates the clinicopathological features of chronic and relapsing experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. NPCs possess tropic properties, maintain multipotency, and can be genetically modified to deliver potentially therapeutic molecules (Gage and Temple, 2013). Therefore, we established a 96-well-based screening system to screen the compound that controlled the proliferation of NPCs. This screening system can be used to screen other compounds that promote cell proliferation and provide new targets for the treatment of neurodegenerative diseases.
Materials and methods
Acknowledgements This work was supported by grants from the National Natural Science Foundation of China (71704136).
Introduction Adenosine acts at four distinct extracellular G-protein-coupled receptors (A1R, A2AR, A2BR, A3R) as an endogenous signaling agent, and participates in physiological, non-physiological (perturbed) and pathological (diseased, dysfunctional) states. It can regulate diverse functions such as cardiovascular, respiratory and renal function, inflammatory and immune events, and CNS events, and there has been considerable interest in developing adenosine-based therapeutics for conditions involving these systems (Jacobson and Gao, 2006; Schenone et al., 2010; Gessi et al., 2011, Chen et al., 2013). A role for adenosine in antinociception was first identified in the 1970s and then elaborated in the 1980s with systemic and spinal (intrathecal, or i.t.) administration of selective agonists. These studies emphasized the role of adenosine A1Rs in producing antinociception, with some effects due to adenosine A2ARs (the only other subtype known at the time) also identified. In the 1990s, adenosine receptor actions at peripheral sites were identified, and actions in nerve injury models for neuropathic pain elaborated. These observations were the subject of several earlier reviews on nociception (Sawynok, 1998, Dickenson et al., 2000, Sawynok and Liu, 2003). During this time period, clinical studies examined effects of intravenous (i.v.) infusions of adenosine and of ATP (which is rapidly metabolized to adenosine in blood) for chronic pain and in a perioperative setting, and these studies have been reviewed specifically (Segerdahl and Sollevi, 1998, Hayashida et al., 2005, Gan and Habib, 2007). Importantly, during the 1990s, A2B- and A3Rs were cloned and adenosine receptor nomenclature was refined to include the four distinct receptors that are currently known (Fredholm et al., 2001, Fredholm et al., 2011. Adenosine has a higher affinity for A1-, A2A- and A3Rs than for A2BRs (Fredholm et al., 2011), but its affinity can vary according to the assay and, in some cases, it has a similar affinity for all four subtypes (Fredholm, 2014).