Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke.
BACKGROUND
The relationship between functional improvements in ischemic rats given a neural stem cell (NSC) transplant and the modulation of the class I major histocompatibility complex (MHC) mediated by NSC-derived neurotrophins was investigated.


METHODS
The levels of gene expression of nerve growth factor (NGF), brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) were assayed from cultures of cortical NSC from Sprague-Dawley rat E16 embryos. The levels of translated NGF in spent culture media from NSC cultures and the cerebral spinal fluid (CSF) of rats with and without NGF injection or NSC transplant were also measured.


RESULTS
We found a significant increase of NGF, BDNF and NT-3 transcripts and NGF proteins in both the NSC cultures and the CSF of the rats. The immunochemical staining for MHC in brain sections and the enzyme-linked immunosorbent assay of CSF were carried out in sham-operated rats and rats with surgically induced focal cerebral ischemia. These groups were further divided into animals that did and did not receive NGF administration or NSC transplant into the cisterna magna. Our results show an up-regulation of class I MHC in the ischemic rats with NGF and NSC administration. The extent of caspase-III immunoreactivity was comparable among three arms in the ischemic rats.


CONCLUSIONS
Readouts of somatosensory evoked potential and the trap channel test illustrated improvements in the neurological function of ischemic rats treated with NGF administration and NSC transplant.
Sun
Chongran
C
Department of Neural Stem Cell, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China.
Zhang
Han
H
Li
Jin
J
Huang
Hua
H
Cheng
Hongbin
H
Wang
Yajie
Y
Li
Ping
P
An
Yihua
Y
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009043:Motor Activity / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044968:Regenerative Medicine / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism*; D020521:Stroke / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D053148:Caspase 3; D001973:Bromodeoxyuridine