title: L-serine treatment may improve neurorestoration of rats after permanent focal cerebral ischemia potentially through improvement of neurorepair.
abstract: The present study was conducted to clarify whether treatment with L-serine can improve the brain repair and neurorestoration of rats after permanent middle cerebral artery occlusion (pMCAO). After pMCAO, the neurological functions, brain lesion volume, and cortical injury were determined. GDNF, NGF, NCAM L1, tenascin-C, and Nogo-A levels were measured. Proliferation and differentiation of the neural stem cells (NSCs) and proliferation of the microvessels in the ischemic boundary zone of the cortex were evaluated. Treatment with L-serine (168 mg/kg body weight, i.p.) began 3 h after pMCAO and was repeated every 12 h for 7 days or until the end of the experiment. L-Serine treatment: 1) reduced the lesion volume and neuronal loss; 2) improved the recovery of neurological functions; 3) elevated the expression of nerve growth-related factors; and 4) facilitated the proliferation of endogenous NSCs and microvessels activated after pMCAO and increased the number of new-born neurons. 5) D-cycloserine, an inhibitor of serine hydroxymethyltransferase, blunted the effects of L-serine on NSC proliferation, differentiation, microvascular proliferation. In conclusions, L-serine treatment in pMCAO rats can reduce brain injury and facilitate neurorestoration which is partly associated with the improvement of proliferation of NSCs and microvessels, reconstruction of neurovascular units and resultant neurorepair. The effects of L-serine on endogenous NSC proliferation and microvascular proliferation are partly mediated by the action of L-serine as a substrate for the production of one-carbon groups used for purine and pyrimidine synthesis and modulation of the expression of some nerve growth-related factors.
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Infectious Diseases, The Third People's Hospital of Nantong, Jiangsu, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Qiang
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China; Department of Neurology, Affiliated Hospital, Nantong University, Jiangsu, China.
authors.forename: Zheng-Lin
authors.initials: ZL
authors.lastname: Jiang
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China; Department of Neurology, Affiliated Hospital, Nantong University, Jiangsu, China.
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Zhao
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China; Department of Neurology, Affiliated Hospital, Nantong University, Jiangsu, China.
authors.forename: Tao-Jie
authors.initials: TJ
authors.lastname: Ren
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Jiangsu, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Xu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D055806:Microvessels / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002491:Central Nervous System Agents; D012694:Serine