How does zebrafish support new strategies for neuroprotection and neuroregeneration in hypoxia-related diseases?

Hypoxia is a condition found commonly in several disorders, such as ischemia, asthma, anemia and neonatal hypoxia. Individuals subjected suddenly to high altitude or extreme exercise are also challenged to low oxygen (O2) levels. Since the brain presents elevated basal O2 consumption, this organ is readily affected by hypoxia. For this reason, cerebral hypoxia has been investigated in different species in order to elucidate the involved molecular mechanisms. Based on these models, it is now understood that many of the neural ischemic events occur in cerebral hypoxia, such as excessive release of chelatable Zn from neurons (Udayabanu et al., 2012), glial activation (Li et al., 2010), depletion in mitochondrial activity, increase in reactive oxygen species and cell necrosis (see review in Lukyanova and Kirova, 2015). Moreover, it has been recently reported that chelatable Zn contribute also to the development of the pathophysiology of hypoxia, triggering neuroinflammatory and oxidative stress responses observed in hypoxia (Malairaman et al., 2014). Thus, potential compounds have been tested on hypoxia models to evaluate new neuroregenerative and neuroprotective therapies able to replace the loss of neural cells and decrease the progression of secondary injuries caused by hypoxia, respectively. To advance the research in hypoxia, we have supported the development of a new model in zebrafish. These animals have been used in large scale screening of neuroprotective drugs, because they present features, such as easy maintenance, low operating cost and functional conservation of mammalian brain areas. Moreover, the sharing of many human genes, including those encoding to hypoxia-inducible factors (HIFs), further supports the adoption of zebrafish to evaluate the effects of hypoxia.