In vivo effects of bumetanide at brain concentrations incompatible with NKCC1 inhibition on newborn DGC structure and spontaneous EEG seizures following hypoxia-induced neonatal seizures

Models of hypoxia and ischemia-induced seizures

“…These models are also used to study the influence of HIE-induced seizures on the postnatal brain development, including the formation and maturation of synapses and neural networks. It is noteworthy that recent evidence of long-term spontaneous seizures and social behavioral deficits in the neonatal hypoxia-induced seizure models (LippmanBell et al, 2013;Rakhade et al, 2011;Talos et al, 2012;Wang et al, 2015) allows further investigations on the mechanisms underlying epileptogenesis and cognitive deficits following perinatal HIE injuries. Using appropriate animal models will continue to contribute to the critical breakthroughs in mechanisms and identification of novel therapeutic treatment targets of seizures/epilepsy following perinatal hypoxic/ischemic encephalopathies in human.…”

“…Rats (Long-Evans rats, Wistar rats and Sprague-Dawley rats) (Jensen et al, 1991(Jensen et al, , 1998Jensen and Wang, 1996;Moshe and Albala, 1985;Rakhade et al, 2008Rakhade et al, , 2011Wang et al, 2015) and mice (Leonard et al, 2013;Rakhade et al, 2012;Rubaj et al, 2003;Wais et al, 2009;Wang et al, 2013;Zanelli et al, 2014) are the most commonly used species, with a recent emerging use of other species, i.e., rabbits (Holtzman et al, 1999;Kekelidze et al, 2000), to study the molecular mechanisms in hypoxia-induced seizures in the immature brain. In rats, hypoxic seizures can only be induced during the critical developmental window, P6-12, which is a period of synaptic maturation and corresponds to the age-dependence of clinical hypoxia-associated neonatal seizures (Chiba, 1985;Jensen et al, 1991Jensen et al, , 1998Leonard et al, 2013;Owens et al, 1997;Rakhade and Jensen, 2009;Rakhade et al, 2011).…”

Bumetanide-induced NKCC1 inhibition attenuates oxygen–glucose deprivation-induced decrease in proliferative activity and cell cycle progression arrest in cultured OPCs via p-38 MAPKs

“…In some animal models with increased levels of NKCC1, and NKCC1 inhibition has been shown to promote recovery from injuries such as middle cerebral artery occlusion, spinal cord injury, epilepsy, and so on and reported to promote cell proliferation in vivo (Chen et al, 2005;Cramer et al, 2008;Robinson et al, 2010;Wang et al, 2015). However, NKCC1 inhibition may also have a negative role in cell cycle regulation in corneal epithelial cells (Wang et al, 2011).…”

Exploring novel AEDs from drugs used for treatment of non-epileptic disorders

“…injected into the rats for 3 weeks at a dose of 0.5 mg/kg. The authors found that this treatment could significantly increase cell proliferation in the hippocampus, increase the number of newborn granule cells as the rats developed, and reduce seizure activity [96].…”