51 research outputs found
Policy Directions & Tasks for the Human Resource Development in Education
๋ณธ ์ฐ๊ตฌ์์๋ ๊ต์ก์ธ์ ์์ ๊ฐ๋ฐ์ ์ฑํจ๋ฅผ ์ข์ฐํ๋ค๊ณ ๋ณผ ์ ์๋ ํต์ฌ์ธ๋ ฅ์ธ 1) ๊ต์, 2) ํ๊ตํ์ ๊ฐ, 3) ๊ต์ก์ ๋ฌธ์ง, 4) ์ผ๋ฐํ์ ์ง, 5) ๋ํ๊ต์, 6) ๋ํํ์ ์ง ๋ฑ ๊ต์ก ๋ถ์ผ์ ์ฃผ์ ํต์ฌ ์ธ๋ ฅ์ ๋์์ผ๋ก ์ธ์ ์์ ๊ฐ๋ฐยท๊ด๋ฆฌ์ ํํฉ๊ณผ ๋ฌธ์ , ๊ทธ๋ฆฌ๊ณ ๊ฐ์ ๋ฐฉ์์ ํ์ํ์๋ค. ๊ตฌ์ฒด์ ์ผ๋ก ๋งํด, ๊ต์ก์ธ์ ์์ ๊ฐ๋ฐยท๊ด๋ฆฌ์ ์ฃผ์๊ณผ์ ์ธ 1) ์์ฑ, 2) ๊ฐ๋ฐ, 3) ํ์ฉ, 4) ์ ์ง ๋ฑ์ ์ธก๋ฉด์์ ์ฐ๋ฆฌ๋๋ผ ๊ต์ก์ธ์ ์์๊ฐ๋ฐ์ ํํฉ ๋ฐ ๋ฌธ์ ์ , ๊ทธ๋ฆฌ๊ณ ์์ผ๋ก์ ๊ฐ์ ๋ฐฉํฅ ๋ฐ ๊ณผ์ ๋ฑ์ ๋ชจ์ํจ์ผ๋ก์จ ์ฐ๋ฆฌ๋๋ผ ๊ต์ก๋ถ์ผ ์ธ์ ์์ ์ ์ฑ
๊ฐ๋ฐ๊ณผ ๋ฐฉํฅ ์ค์ ์ ์์ฌ์ ์ ์ ๊ณตํด ๋ณด๊ณ ์ ํ์๋ค.โ
. ์ฐ๊ตฌ์ ๊ฐ์ 1
1. ์ฐ๊ตฌ ํ์์ฑ ๋ฐ ๋ชฉ์ 1
2. ์ฐ๊ตฌ์ ๋ด์ฉ๊ณผ ๋ฒ์ 2
3. ์ฐ๊ตฌ๋ฐฉ๋ฒ 3
โ
ก. ์ดยท์ค๋ฑ ๊ต์ฌ์ ํ๋ณด์ ๊ฐ๋ฐ 5
1. ์ ์ค 5
2. ๊ต์ฌ์ ํ๋ณด, ๊ฐ๋ฐ์ ํํฉ 5
3. ๊ต์ฌ์ ํ๋ณด, ๊ฐ๋ฐ์ ๋ฌธ์ ์ 17
4. ์ฃผ์๊ตญ์ ๊ต์ฌ ์์ฑ 27
5. ๊ต์ฌ์ ํ๋ณด, ๊ฐ๋ฐ์ ๋ฐ์ ๋ฐฉํฅ 28
6. ์ ๊ฒฐ 34
โ
ข. ๋ํ๊ต์์ ํ๋ณด์ ๊ฐ๋ฐ 35
1. ์ ์ค 35
2. ๊ต์์์ ์ธ์ ์์ ๊ฐ๋ฐ 35
3. ํํฉ ๋ฐ ๋ฌธ์ ์ 38
4. ์ฃผ์๊ตญ์ ๋ํ ๊ต์ 45
5. ๋ฐ์ ๋ฐฉํฅ ๋ฐ ๊ณผ์ 52
6. ์ ๊ฒฐ 57
โ
ฃ. ํ๊ตํ์ ๊ฐ์ ํ๋ณด์ ๊ฐ๋ฐ 59
1. ์ ์ค 59
2. ํ๊ตํ์ ๊ฐ ํ๋ณด ๋ฐ ๊ฐ๋ฐ์ ํํฉ๊ณผ ๋ฌธ์ ์ 60
3. ์ฃผ์๊ตญ์ ํ๊ตํ์ ๊ฐ ์์ฑ ๋ฐ ๊ฐ๋ฐ 67
4. ํ๊ตํ์ ๊ฐ์ ์์ฑ ๋ฐ ๊ฐ๋ฐ ๋ฐฉํฅ 74
5. ์ ๊ฒฐ 80
โ
ค. ๊ต์ก์ ๋ฌธ์ง์ ํ๋ณด์ ๊ฐ๋ฐ 85
1. ์ ์ค 85
2. ๊ต์ก์ ๋ฌธ์ง์ ์ญํ ๊ณผ ์
๋ฌด 87
3. ๊ต์ก์ ๋ฌธ์ง์ ์์ง๊ณผ ์๊ฒฉ 92
4. ์ฃผ์๊ตญ์ ๊ต์ก์ ๋ฌธ์ง 95
5. ๊ต์ก์ ๋ฌธ์ง์ ์ธ๋ ฅ๊ด๋ฆฌ ํํฉ ๋ฐ ๋ฌธ์ ์ 101
6. ๊ต์ก์ ๋ฌธ์ง์ ํ๋ณด์ ๊ฐ๋ฐ์ ์ํ ๋ฐฉํฅ ๋ฐ ๊ณผ์ 109
7. ์ ๊ฒฐ 116
โ
ฅ. ๋ํํ์ ์ง์ ํ๋ณด์ ๊ฐ๋ฐ 117
1. ์ ์ค 117
2. ๋ํํ์ ๊ด๋ฆฌ์ง์ ํํฉ ๋ฐ ๋ฌธ์ ์ 118
3. ์ฃผ์๊ตญ์ ๋ํํ์ ์ง 122
4. ๋ํํ์ ๊ด๋ฆฌ ํ์ ์ ์ํ ๊ธฐ๋ฐ์กฐ์ฑ 128
5. ๋ํํ์ ๊ด๋ฆฌ์์ ์๊ฒฉ๊ณผ ํต์ฌ์ญ๋์ ๊ฐ๋ฐ๊ณผ์ 134
6. ์ ๊ฒฐ 137
โ
ฆ. ๊ต์กํ์ ์ง์ ํ๋ณด์ ๊ฐ๋ฐ 139
1. ์ ์ค 139
2. ๊ต์กํ์ ์ง์ ๊ฐ๋
๊ณผ ๊ท๋ชจ 140
3. ํํฉ 142
4. ์ฃผ์ ๋ฌธ์ ์ 153
5. ๊ต์กํ์ ์ง ์ธ์ ์์๊ฐ๋ฐ ์ ์ฑ
๋ฐฉํฅ๊ณผ ๊ณผ์ 156
6. ์ ๊ฒฐ 160
โ
ง. ๊ฒฐ๋ก ๋ฐ ์ ์ธ 161
์ฐธ๊ณ ๋ฌธํ 16
A Study on The Infra Construction of National Human Resource Development
21์ธ๊ธฐ ๊ตญ๊ฐ ์ ๋ต์ฌ์
์ ์ผํ์ผ๋ก ๊ตญ๊ฐ์ธ์ ์์์ ๊ฐ๋ฐ์ ์ธํ๋ผ ๊ตฌ์ถ์ ์ํด์๋ ์ธ์ ์์๊ฐ๋ฐ๊ณผ ๊ด๋ จํ ์ ๋ฐ ์ฌํญ๋ค์ด ์ข
ํฉ์ ์ผ๋ก ์ฌ๊ฒํ ๋์ด์ผ ํ๋ค. ์ด๋ฅผ ์ํด์๋ ๊ต์กํ์ ์ฒด์ ์ ๋ํ ์ ๋ฉด์ ์ธ ์ง๋จ๊ณผ ๋ถ์์ด ์๊ตฌ๋๋ฉฐ, ๊ต์๊ฐ๋ฐ์ฒด์ ์ ์๋ก์ด ๊ตฌ์ถ, ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ์ ๋ถ ๋ถ์ฒ๊ฐ ์กฐ์ ๊ณผ ํ๋ ฅ์ ๋น๋กฏํ ๊ด๋ จ ๋ฒ๋ น์ ์ฌ์ ๋น๊ฐ ์์ฒญ๋๋ฉฐ, ์์ธ๋ฌ ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ํฌ์์ ์ฌ์์ ์ฐ์ ์์๊ฐ ์๊ธํ ์ฌ๊ฒํ ๋์ด์ผ ํ๋ค. ๋ฐ๋ผ์, ๋ณธ ์ฐ๊ตฌ๋ ์ด์ ๊ฐ์ ๊ฐ๊ฐ์ ๊ณผ์ ์ ๋ํ ๋์๋ค์ด ๊ตฌ์ํ๊ณ ์ ์ํจ์ผ๋ก์จ ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ ๋ต ์๋ฆฝ๊ณผ ์ถ์ง์ ์ํ ๊ธฐ์ด์ ์ธ ์ ๋ณด์ ์๋ฃ๋ฅผ ์ ๊ณตํ๋ ๋ฐ ์ฃผ์์ ์ ๋๊ณ ์ ํ๋ค.Recently the government came up with the National Human Resources Development(NHRD) policy. The South Korean government has adopted the NHRD as an essential project. Because the efficient training and use of the NHR upgrade the quality of life and national competitiveness. That is to say, it is the NHRD that can develop human potentiality and ability throughout the social system. It is imperative to establish the social infra system that would play a role in the training, placement and use of the NHR in the future for its efficient operation . Until now, studies on the NHRD have been limited to specific scholars or organizations. More profound researches and studies have to be prevailed for improving the NHRD. In this paper, in order to clear the way of developing human resources, we have taken five issues: 1) the construction of educational administration system, 2) the establishment of teacher training system, 3) the adjustment and cooperation among the government organizations, 4) the investigation of laws and regulations related to the NHRD and 5) the investment and the financial resource for the NHRD.
First, we study the educational administration system at the level of the central government and the local government respectively. Nationally, we study the educational administration structure of the central government and locally, do we focus on the interrelationship with the central one. In addition, we went over the drive system of local government's NHRD policy.
Second, in order to establish the teacher training system, considering the educational contents of teachers and their human resource, we suggested the establishment of the teacher evaluation system, the enforcement of the teacher's licence test, the enactment of standard curriculum for the teacher training, practice education enforcement as institution of the probationary period, and the change of the performance-oriented research study.
Third, through the adjustment and cooperation among the government organizations, the government can make the best use of the NHRD policy. Overlapped policies must be adjusted to one organization and, if necessary, intense cooperation between the organizations also ought to be made. On the basis of this adjustment and cooperation, we study four fields : 1) connecting job training to related work, 2) training professional human resources and supporting R&D in national strategic field, 3) developing woman resources and their application on the field . 4) developing vulnerable youths and physically challenged peoplen To achieve these purposes, our research shows that the government need to make a use of internet, publicize the importance of the NHRD, share the information of the NHR with people, reorganize the government, revaluate the NHRD policy regularly, and maximize the autonomy of the private sector.
Fourth, we investigate laws and regulations related to the NHRD and propose some solutions. We study the Education Basic Law (the legislation of basic articles about job education, the problem of religion education in primary and secondary school), the Primary and Secondary Education Law(the enactment of various school systems, government designed textbook, controversial point and assignment of the merger and abolition of the schools), the Higher Education law, the Life-long Education and Training Law and so on .
Last, we study the necessary investment and the financial resource for the NHRD, the priority and the method for the investment. The priority
of the investment is to finance basic social utilities and database on information society, higher quality human resources, and the undeveloped areas and lower class for the purpose of unifying the society. In addition, there are two methods in the NHRD for the government. One is to invest directly and the other is to compensate private sector investment which needs to examined seriously.
For Infra construction for the NHRD, we have studied five fields, analysed the situation, and produced the alternatives. However, these tasks too serious to be reached independently further. Anyway there are enough reasons the government must invest the manpower and human resources to develop the national competitiveness and the quality of life.์ฐ๊ตฌ์์ฝ
โ
. ์ ๋ก 1
1. ์ฐ๊ตฌ์ ํ์์ฑ ๋ฐ ๋ชฉ์ 1
2. ์ฐ๊ตฌ๋ด์ฉ ๋ฐ ๋ฐฉ๋ฒ 4
3. ์ฐ๊ตฌ์ ๋ฒ์์ ํ๊ณ 5
โ
ก. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ๊ต์กํ์ ์ฒด์ ์ ๊ตฌ์ถ 7
1. ์ธ์ ์์๊ฐ๋ฐ์ ๊ฐ๋
๊ณผ ์๋ฏธ 7
2. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ์ธํ๋ผ ๊ตฌ์ถ ๊ณผ์ 16
3. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ๊ต์กํ์ ์ฒด์ ๊ตฌ์ถ 19
โ
ข. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ๊ต์๊ฐ๋ฐ์ฒด์ ์ ๊ตฌ์ถ 29
1. ๊ต์๊ฐ๋ฐ์ ์ํ ๋ชจํ๊ณผ ๊ธฐ์ค 29
2. ์ธ์ ์์๊ฐ๋ฐ ๊ด์ ์์์ ๊ต์๊ฐ๋ฐ์ฒด์ ๊ตฌ์ถ๋ฐฉ์ 33
โ
ฃ. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ์ ๋ถ ๋ถ์ฒ๊ฐ ์กฐ์ ๊ณผ ํ๋ ฅ 43
1. ๋ฌธ์ ์ธ์ 43
2. ๋ถ์์ ์ค๊ฑฐ์ ๋์ 46
3. ์คํ ๋ถ์ ๊ฒฐ๊ณผ 48
4. ์ ๋ถ๋ถ์ฒ๊ฐ ์กฐ์ ๊ณผ ํ๋ ฅ์ ์ํ ๊ณผ์ 59
โ
ค. ๊ตญ๊ฐ์ธ์ ์์ ๊ฐ๋ฐ์ ์ํ ๊ด๋ จ ๋ฒ๋ น์ ๊ฒํ ์ ๊ณผ์ 63
1. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ ๊ด๋ จ ๋ฒ๋ น์ ์ฒด๊ณ 64
2. ๋ฒ๋ น ๊ฒํ ๋ฐ ์ ๋น์ ๊ธฐ๋ณธ ์๋ฆฌ 75
3. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ ๊ด๋ จ ๋ฒ๋ น์ ๊ฒํ ์ ๊ณผ์ 80
โ
ฅ. ๊ตญ๊ฐ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ํฌ์์ ์ฌ์ 91
1. ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ํฌ์์ ํ์์ฑ 91
2. ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ํฌ์์ ์ฐ์ ์์ 93
3. ์ธ์ ์์๊ฐ๋ฐ์ ์ํ ํฌ์์ ๋ฐฉ๋ฒ 106
โ
ฆ. ์์ฝ ๋ฐ ๊ฒฐ๋ก 111
์ฐธ๊ณ ๋ฌธํ 115
ABSTRACT 12
O-GlcNAcylation of RIPK1 rescues red blood cells from necroptosis
Necroptosis is a type of cell death with excessive inflammation and organ damage in various human diseases. Although abnormal necroptosis is common in patients with neurodegenerative, cardiovascular, and infectious diseases, the mechanisms by which O-GlcNAcylation contributes to the regulation of necroptotic cell death are poorly understood. In this study, we reveal that O-GlcNAcylation of RIPK1 (receptor-interacting protein kinase1) was decreased in erythrocytes of the mouse injected with lipopolysaccharide, resulting in the acceleration of erythrocyte necroptosis through increased formation of RIPK1-RIPK3 complex. Mechanistically, we discovered that O-GlcNAcylation of RIPK1 at serine 331 in human (corresponding to serine 332 in mouse) inhibits phosphorylation of RIPK1 at serine 166, which is necessary for the necroptotic activity of RIPK1 and suppresses the formation of the RIPK1-RIPK3 complex in Ripk1 -/- MEFs. Thus, our study demonstrates that RIPK1 O-GlcNAcylation serves as a checkpoint to suppress necroptotic signaling in erythrocytes.ope
Neurorestoration induced by mesenchymal stem cells: potential therapeutic mechanisms for clinical trials
Stem cells are emerging as therapeutic candidates in a variety of diseases because of their multipotent capacities. Among these, mesenchymal stem cells (MSCs) derived from bone marrow, umbilical cord blood or adipose tissue, comprise a population of cells that exhibit extensive proliferative potential and retain the ability to differentiate into multiple tissue-specific lineage cells including osteoblasts, chondrocytes, and adipocytes. MSCs have also been shown to enhance neurological recovery, although the therapeutic effects seem to be derived from an indirect paracrine effect rather than direct cell replacement. MSCs secrete neurotrophic factors, promote endogenous neurogenesis and angiogenesis, encourage synaptic connection and remyelination of damaged axons, decrease apoptosis, and regulate inflammation primarily through paracrine actions. Accordingly, MSCs may prevail as a promising cell source for cell-based therapy in neurological diseases.ope
DNA double-strand break-free CRISPR interference delays Huntington's disease progression in mice
Huntingtonโs disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. CRISPR-Cas9 nuclease causes double-strand breaks (DSBs) in the targeted DNA that induces toxicity, whereas CRISPR interference (CRISPRi) using dead Cas9 (dCas9) suppresses the target gene expression without DSBs. Delivery of dCas9-sgRNA targeting CAG repeat region does not damage the targeted DNA in HEK293T cells containing CAG repeats.
When this study investigates whether CRISPRi can suppress mutant HTT (mHTT), CRISPRi results in reduced expression of mHTT with relative preservation of the wild-type HTT in human HD fibroblasts. Although both dCas9 and Cas9 treatments reduce mHTT by sgRNA targeting the CAG repeat region, CRISPRi delays behavioral deterioration and protects striatal neurons against cell death in HD mice. Collectively, CRISPRi can delay disease progression by suppressing mHtt, suggesting DNA DSB-free CRISPRi is a potential therapy for HD that can compensate for the shortcoming of CRISPR-Cas9 nuclease.ope
Fibroblast Growth Factor-2 Induced by Enriched Environment Enhances Angiogenesis and Motor Function in Chronic Hypoxic-Ischemic Brain Injury
This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1ยฎ mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and ฮฑ-smooth muscle actin (ฮฑ-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of ฮฑ-SMA+ and PECAM-1+ cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by upregulation of FGF-2 in chronic hypoxic-ischemic brain injury.ope
Induction of Striatal Regeneration Delays Motor Deterioration in a Mouse Model of Huntingtonโs Disease
Intraventricular administration of brain-derived neurotrophic factor (BDNF) can induce striatal neurogenesis.
Epidermal growth factor (EGF), by expanding the mitotic pool of neural stem/progenitor cells in the subventricular
zone (SVZ) responsive to neuronal instruction by BDNF, can potentiate this process. The objective of
this study was to investigate the induction of striatal regeneration and consequent functional benefits after chronic
infusion of BDNF and EGF in a R6/2 transgenic mouse model of Huntingtonโs disease (HD). At 6 weeks of age, the
mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments
into the ventricle: combination of BDNF and EGF (B/E), BDNF, EGF, or phosphate buffered saline (PBS). Two
weeks after treatment, the B/E-treated mice revealed a significant increase of new neurons co-stained with BrdU and
ฮฒIII-tubulin in the ventricular side of neostriata (VZ~300 ฮผm), compared with PBS controls. The newly generated
cells were also expressed as migrating neuroblasts co-labeled with doublecortin or PSA-NCAM in the SVZ. The survival
rates of the new neurons were in the range of 30~50% at 6 weeks after treatment. For behavioral assessments,
the B/E combination therapy group showed a significant delay in motor deterioration relative to PBS controls in both
constant and accelerating rotarod as well as locomotor activity test 6 weeks after treatment. However, administration
of BDNF alone did not exhibit significant delays in motor deterioration in most of behavioral assessments. Neither
did motor performance improve in R6/2 mice treated only with EGF. In conclusion, induction of striatal regeneration
by the intraventricular administration of BDNF and EGF delayed disease progression in HD. Therefore, this treatment
may offer a promising strategy for restoration of motor function in HDope
A Study on the Usage of Miร o(ๅป) and Gลng(ๅฎฎ) in Zhou Dynasty through the Mentions to Them in the Scripture Sentences of ใChลซn-qiลซ(ๆฅ็ง)ใ - In the Process of Investigating the Existence of Zhou Dynasty's System to Regulate the Number of Zลng-miร o(ๅฎๅป)ใ1/2ใ
A Study on the Origin of โthe System to Regulate the Number of Zลng-miร os that Each Class Could Ownโ โ Focusing on the Discussion on the System Regulating the Number of Zลng-miร os in Han Dynasty and Warring State Period
๋ํํ ๋ง์ฐ์ค ๋ชจ๋ธ์์ ์ฌํ๋ก๊ทธ๋๋ฐ ์ธ์์ ์์ฒด๋ด ๋ฐํ์ ํตํ ์ฑ์๊ต์ธํฌ์ ์น๋ฃ ๊ฐ๋ฅ์ฑ
์๊ณผํCerebral ischemia and stroke can lead incurable brain damage or death. Astrocytes, one of the most abundant cells in the brain, are activated by injury such as ischemia. Reactive astrocytes, in particular, play a crucial role in recovery from brain injury. Four reprogramming factors (Pou5f1, Sox2, Myc, and Klf4) expression have been used to convert cell types, but it has rarely been studied promoting functional recovery by expression of reprogramming factors in ischemic injury. The aim of this study is therefore to determine whether in vivo transient expression of reprogramming factor can improve neurobehavioral function. Cerebral ischemia was induced by two methodsโtransient bilateral common carotid artery occlusion (BCCAO) and permanent unilateral common carotid artery ligation with hypoxia (8% O2)โafter which brains were treated (in the lateral ventricle or striatum) with doxycycline (DOX) in transgenic mice in which the four reprogramming factors were expressed by doxycycline. Either doxycycline (DOX-1; 1 ฮผg/ml, DOX-100; 100 ฮผg/ml) or phosphate-buffered saline (PBS) was then infused into the brain via an osmotic pump for 7 days. In the BCCAO model, histologic evaluation showed that this transient expression of reprogramming factor induced the proliferation of astrocytes and neural progenitors, while neurons and glial scar formation was not observed. Furthermore, in vivo expression of reprogramming factor caused neuroprotective effects and angiogenesis in the striatum. Tumor formation was not observed in any group. Importantly, the rotarod and ladder walking tests showed to promote functional restoration from ischemic damage via the expression of the four reprogramming factors. To elucidate the therapeutic mechanisms associated with astrogliosis, RNA sequencing analysis was performed in order to identify a transcriptome that was significantly changed in the DOX-100 group compared to PBS group. Among downregulated genes (complement C3, C4a, C4b, C1qa, C1qb and C1qc) and astrocyte markers (GFAP, Vimentin and S100ฮฒ) were validated using qRT-PCR. Because C3 is a detrimental astrocyte marker, C3 in particular was measured using histologic analysis. The results showed that C3 was significantly reduced in DOX-100 treated mice compared with the DOX-1 and PBS groups. A hypoxic-ischemic (HI) model, a stroke model used in another experimental group, was used to compare efficacy of reprogrammed expression in two areas of the brain, the ventricle and striatum. That results showed that the astrocytes and neural progenitors were significantly proliferated, but not neurons or glial scar, and the condition of blood vessels in the injured brain was improved following in vivo reprogramming factor expression. Furthermore, in vivo reprogramming factor expression was protective of neurons under hypoxic ischemic conditions. Notably, neurobehavioral evaluations such as the grip strength, cylinder, ladder walking and open field tests showed functional recovery was dramatically improved via the expression of the four reprogramming factors in the lateral ventricle. Interestingly, the expression of the reprogramming factors in the striatum did not lead to changes in neurological function in any group. In the rotarod test, there were no significant differences in both the lateral ventricular-targeted and striatum-targeted group. Tumor development was not observed in the lateral ventricle-targeted group, but the striatum-targeted group showed that abnormal cell proliferation in DOX-100 treated mice brain. Furthermore, treatment with DOX-1,000 (doxycycline; 1,000 ฮผg/ml) lead to tumor formation in the striatum-targeted group. Taken together, newly generated astrocytes are essential for protecting neurons from damage following cerebral ischemia (BCCAO and HI mouse model) and for enhancing blood vessels. These results show that a therapeutic potential of methods that aim to improve functional recovery by reducing reactive astrocytes (harmful A1 astrocytes) in BCCAO mouse models. In the HI mouse model, we noted a recovery effect in the group in which the lateral ventricle was targeted with the expression of reprogramming factors, but not in the striatum-targeted group. Therefore, targeting the lateral ventricle for expression of reprogramming factors may offer better therapeutic results.open๋ฐ
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