Neuroprotective effects of human neural stem cells over-expressing choline acetyltransferase in a middle cerebral artery occlusion model

Publication date: January 2020Source: Journal of Chemical Neuroanatomy, Volume 103Author(s): Jihyun Kim, Kyungha Shin, Yeseul Cha, Young-Hwan Ban, Sung Kyeong Park, Heon Sang Jeong, Dongsun Park, Ehn-Kyoung Choi, Yun-Bae KimAbstractStroke is one of the most-devastating brain diseases causing acute death or permanent disability. Although tissue-type plasminogen activator was approved by Food and Drug Administration for early reperfusion of the occluded vessels, oxidative injury may cause extensive brain infarction. Accordingly, there is a need for effective neuroprotection during reperfusion, and stem cell-based therapeutic approaches should fulfill this requirement. We established human neural stem cells (NSCs) encoding gene of choline acetyltransferase (F3.ChAT), an acetylcholine-synthesizing enzyme, and investigated whether infusion of the F3.ChAT cells attenuate the ischemia-reperfusion brain damage in a rat model of middle cerebral artery occlusion (MCAO). F3.ChAT cells were found to produce much higher amounts of ChAT as well as neuroprotective and anti-inflammatory neurotrophins than their parental F3 NSCs. After 2-h occlusion, the artery was reperfused, along with intravenous infusion of the stem cells (1 × 106 cells/rat). Administration of the F3.ChAT cells markedly reduced the infarction volume and improved both the cognitive dysfunction and behavioural deficits of MCAO animals, in which F3.ChAT cells were superior to F3 cells. F3.ChAT cells not only restored microt...
Source: Journal of Chemical Neuroanatomy - Category: Neuroscience Source Type: research