Once an arm was chosen, the rat was placed in the stem of the maze again, and the trial repeated. neurological function while significantly increasing neutrophil counts. On the other hand, the G-CSF+Ab group significantly reduced infarct volume, improved neurological function and decreased neutrophil counts. The Ab alone group showed reversal of the neuroprotective effects of the G-CSF+Ab group. No significant differences were found in peripheral organ weights between groups. Conclusion Our data suggest that coadministration of G-CSF with Ab not only prevented brain atrophy but also significantly improved neurological function by decreasing blood neutrophil counts. Hence the neuroprotective effects of G-CSF may be further enhanced if neutrophilia is usually avoided. Keywords: Granulocyte- colony stimulating factor (G-CSF), Anti-neutrophil antibody (Ab), Hypoxia- ischemia (HI), Neurological function, Neutrophil, Neonatal Introduction Hypoxia ischemia (HI) refers to the insufficient blood and oxygen supply to the brain that results in severe brain damage and the development of neurological impairments such as cerebral palsy; cognitive, behavioral, socialization and learning difficulties; seizures and encephalopathy. It is the main cause of mortality and morbidity in infants; affecting two to four of 1000 full-term births and nearly 60% of premature births (Bracewell and Marlow 2002; Ferriero 2004; Vannucci and Vannucci 1997; Volpe 2001). Current clinical treatments available such as anticonvulsants, therapeutic hypothermia, and fluid and electrolyte management, have proven only some Rabbit Polyclonal to APBA3 degree of success (Koenigsberger 2000; Zanelli, et al. 2009), thus the necessity for alternative strategies to either replace or amplify the current therapeutic protocols. Granulocyte C colony stimulating factor (G-CSF), a 20-kDa hematopoietic growth factor, stimulates survival, proliferation and Cyclovirobuxin D (Bebuxine) development of neuronal stem cells and regulates maturation and survival of neutrophil granulocyte precursors (Roberts 2005; Schneider, et al. 2005; van Raam, et al. 2008). G-CSF has anti-apoptotic (Komine-Kobayashi, et al. 2006; Schabitz, et al. 2003; Schneider, et al. 2005) and anti-inflammatory (Gibson, et al. 2005) effects and has been shown to confer neuroprotection in a number of in vivo studies (Popa-Wagner, et al. 2010; Solaroglu, et al. 2009; Solaroglu, et al. 2006; Yata, et al. 2007). Rats treated with G-CSF tend to have lower infarct volumes, less brain tissue loss and improved long term neurological function (Beck, et al. 2003; Fathali, et al. 2010). However, G-CSF has been identified as the main component in the generation of neutrophilic granulocytes and is in widespread clinical use for the treatment of neutropenia (Schabitz, et al. 2010). G-CSF in conjunction with HI further increases the upregulation of endothelial cell adhesion molecules which captures circulating neutrophils (Justicia, et al. 2003; Vemuganti, et al. 2004). Neutrophils aggregate into cerebral microvasculature leading to breakdown of blood flow and may worsen brain damage (del Zoppo and Mabuchi 2003; Stoll, et al. 1998). A number of studies have shown, both in adult and neonatal animal models of cerebral ischemia, that neutrophils accumulate within cerebral blood vessels and then extravasate into the brain parenchyma (Barone, et al. 1991; Garcia, et al. 1994; Matsuo, et al. 1994; Shiga, et al. 1991). There is evidence that neutrophils Cyclovirobuxin D (Bebuxine) contribute to ischemic injury in adult and Cyclovirobuxin D (Bebuxine) neonatal animals as neutrophil depletion has been reported to be markedly protective (Heinel, et al. 1994; Hudome, et al. 1997; Matsuo, et al. 1994; Shiga, et al. 1991). No study to date has examined whether the neuroprotective Cyclovirobuxin D (Bebuxine) effects of combined treatment with G-CSF and anti-neutrophil antibody (Ab) can translate into decreasing infarct volumes and brain tissue loss, associated with improvements in neurological function, or whether there is an additive benefit against systemic organ atrophy. This study aims to investigate.
Once an arm was chosen, the rat was placed in the stem of the maze again, and the trial repeated
