title: Sodium Butyrate, a Histone Deacetylase Inhibitor, Exhibits Neuroprotective/Neurogenic Effects in a Rat Model of Neonatal Hypoxia-Ischemia.
abstract: Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunctions. Currently, there are no well-established treatments to reduce brain damage and its long-term sequel in infants. Recently, reported data show that histone deacetylase inhibitors provide neuroprotection in adult stroke models. However, the proof of their relevance in vivo after neonatal HI brain injury remains particularly limited. In the present study, we show neuroprotective/neurogenic effect of sodium butyrate (SB), one of histone deacetylase inhibitors (HDACis), in the dentate gyrus of HI-injured immature rats. Postnatal day 7 (P7) rats underwent left carotid artery ligation followed by 7.6 % O2exposure for 1 h. SB (300 mg/kg) was administered in a 5-day regime with the first injection given immediately after the onset of HI. The damage of the ipsilateral hemisphere was evaluated by weight deficit. Newly produced cells were labeled with BrdU, at 50 mg/kg, injected twice daily for 3 consecutive days. Subsequent differentiation of the newborn cells was investigated 2 and 4 weeks after the insult by immunohistochemistry using neuronal and glial cell-lineage markers and BrdU incorporation. Finally, we performed several behavioral tests to evaluate functional outcome. In summary, SB led to a remarkable reduction of the brain damage caused by HI. Moreover, the application of this HDACi protected against HI-induced loss of neuroblasts and oligodendrocyte precursor cells, as well as against neuroinflammation. The observed neuroprotective action suggests that SB may serve as a potential candidate for future treatment of HI-evoked injury in neonates.
authors: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland.
authors: Malgorzata
authors: M
authors: Ziemka-Nalecz
authors: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland.
authors: Joanna
authors: J
authors: Jaworska
authors: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland.
authors: Joanna
authors: J
authors: Sypecka
authors: Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors: Rafał
authors: R
authors: Polowy
authors: Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors: Robert K
authors: RK
authors: Filipkowski
authors: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland. terezal@imdik.pan.pl.
authors: Teresa
authors: T
authors: Zalewska
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D056572:Histone Deacetylase Inhibitors; D018696:Neuroprotective Agents
keywords: Histone deacetylase inhibitors; Neonatal hypoxia-ischemia; Neurogenesis; Neuroprotection; Oligodendrocytes; Sodium butyrate