Protective Effects ofN-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

Abstract

Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects of N-acetyl-l-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia

“…Neonates were obtained from natural delivery, and male pups of post-natal day (PND) 7 underwent HIL; i.e. their left common carotid artery was occluded and placed in an 8% oxygen/92% nitrogen incubator (36°C) for 2 hours 18 , 32 . Finally, the pups were intraperitoneally injected with LPS after 1-hour recovery to induce inflammation, and returned to their dam.…”

“…Each animal was individually placed in a glass cylinder (21 cm in diameter, 34 cm in height) for 3 min. The weight-bearing forepaw to contact the cylinder wall during a full rear was recorded as left (normal), right (impaired), or both 18 , 35 . Paw preference was calculated as [(normal forepaw–impaired forepaw)/(normal forepaw + impaired forepaw + both) × 100%].…”

“…Motor balance and coordination were evaluated using a rotarod test system (Panlab Technology, Barcelona, Spain) at PND14, 20, 30, and 40. Rats were placed on a rotating rod at a constant speed of 12 rpm, and the time for the rats to fall off the rod was recorded 18 , 35 , 36 . The average latency was calculated from three consecutive measurements.…”

“…Current therapeutic strategies are very limited and restricted to supportive intensive care. For example, clinical hypothermia 14 – 16 and experimental administration with erythropoietin, minocycline or N -acetyl-L-cysteine 17 – 19 were found to delay the progress of bodily dysfunction. Recent research has reported that various stem cells such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and multipotent progenitor cells have beneficial effects on HI brain injury 20 – 23 .…”

Analysis of using of citicoline in term newborns during the acute period of hypoxic ischemic encephalopathy

“…N-ацетил-L-цистеїн є потужним антиоксидантом і попередником глутатіону; знижує запалення і покращує виживання клітин [18]. Поліфенолице молекули, присутні у фруктах і травах, мають протизапальні та регенеративні властивості.…”