Neurogenesis, Stroke and Brain Aging

Abstract

Abstract:

Brain aging, a common induced factor of neurodegenerative diseases, is associated with a striking increase in the incidence of stroke, which is a common disease of the nervous system and a major cause of disability and death among those aged 70 years and older. It is well documented that there are more serious brain ischemic changes, larger infarction area and more significant nerve dysfunction in elderly. Although many studies have confirmed decreased neurogenesis in aging brain, increased neurogenesis after stroke holds great promise for brain repair. This review seeks to integrate briefly what is known about neurogenesis and ischemic stroke after brain aging.

Key words: Neurogenesis; aging; Ischemic stroke; Neural stem cells

摘要：

大脑老化是神经退行性疾病的主要诱因。而卒中不仅是老年人的神经系统常见疾病，而且也是70岁以上老年人致残和死亡的重要原因，因此，大脑老化与卒中发病息息相关。已经证实，老年卒中患者其缺血性脑组织损伤更加严重、脑梗死面积更大、缺血后的神经功能障碍也更加显著。尽管研究已证实老龄大脑的神经再生减少，但卒中可以诱导神经再生并能有效促进神经功能恢复，这就为神经再生治疗卒中开辟了良好的途径。本文重点就大脑老化及老化后神经再生、缺血性卒中作一简要综述。

关键词: 神经再生; 老化; 神经干细胞

ZHANG Hong-Xia*, SHAO Bei, WANG Liu-Qing, LIN Zhen-Zhen, XIAO Li, JIANG Hui-Gang, CHENG Yi-Fan, SU Qiao-Er, ZHEN Wei-Ming,ZHUGE Qi-Chuan, JIN Kun-Lin.. Neurogenesis, Stroke and Brain Aging[J]. Chinese Journal of Stroke, 2013, 8(02): 147-152.

张红霞1，邵蓓1，王柳清1，林真珍1，肖丽1，蒋慧刚1，程一帆1，苏巧尔1，郑伟明2，诸葛启钏2，. 大脑老化与神经再生和卒中[J]. 中国卒中杂志, 2013, 8(02): 147-152.

References

Arnold KG. Cerebral blood flow in geriatrics-a review[J]. Age Ageing, 1981, 10:5-9.

Ramirez-Lassepas M. Stroke and the aging of the brain and the arteries[J]. Geriatrics, 1998, 53 Suppl 1:S44-48.

Yankner BA, Lu T and Loerch P. The aging brain[J]. Annu Rev Pathol, 2008, 3:41-66.

Popa-Wagner A, Carmichael ST, Kokaia Z, et al. The response of the aged brain to stroke:too much, too soon?[J]. Curr Neurovasc Res, 2007, 4:216-227.

Jin K, Sun Y, Xie L, et al. Neurogenesis and aging:FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice[J]. Aging Cell, 2003, 2:175-183.

Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors[J]. Cell, 2002, 110:429-441.

Jin K. Modern biological theories of aging[J]. Aging Dis, 2010, 1:72-74.

Davidovic M, Sevo G, Svorcan P, et al. Old age as a privilege of the "selfish ones"[J]. Aging Dis, 2010, 1:139-146.

van Heemst D. Insulin, IGF-1 and longevity[J]. Aging Dis, 2010, 1:147-157.

Cornelius E. Increased incidence of lymphomas in thymectomized mice-evidence for an immunological theory of aging[J]. Experientia, 1972, 28:459.

Brys K, Vanfleteren JR, Braeckman BP. Testing the rate-of-living/oxidative damage theory of aging in the nematode model Caenorhabditis elegans[J]. Exp Gerontol, 2007, 42:845-851.

Hulbert AJ, Pamplona R, Buffenstein R, et al. Life and death:metabolic rate, membrane composition, and life span of animals[J]. Physiol Rev, 2007, 87:1175-1213.

Bjorksten J. The crosslinkage theory of aging[J]. J Am Geriatr Soc, 1968, 16:408-427.

Gerschman R, Gilbert DL, Nye SW, et al. Oxygen poisoning and x-irradiation:a mechanism in common[J]. Science, 1954, 119:623-626.

Harman D. Aging:a theory based on free radical and radiation chemistry[J]. J Gerontol, 1956, 11:298-300.

McCay CM. Iodized salt a hundred years ago[J]. Science, 1935, 82:350-351.

Schulz TJ, Zarse K, Voigt A, et al. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress[J]. Cell Metab, 2007, 6:280-293.

Ferron SR, Marques-Torrejon MA, Mira H, et al. Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis[J]. J Neurosci, 2009, 29:14394-14407.

Djojosubroto MW, Choi YS, Lee HW, et al. Telomeres and telomerase in aging, regeneration and cancer[J]. Mol Cells, 2003, 15:164-175.

Dye CA, El Shawa H, Huffman KJ. A lifespan analysis of intraneocortical connections and gene expression in the mouse II[J]. Cereb Cortex, 2011, 21:1331-1350.

Dye CA, El Shawa H, Huffman KJ. A lifespan analysis of intraneocortical connections and gene expression in the mouse I[J]. Cereb Cortex, 2011, 21:1311-1330.

Huffman K. The developing, aging neocortex:how genetics and epigenetics influence early developmental patterning and age-related change[J]. Front Genet, 2012, 3:212.

Li N, Bates DJ, An J, et al. Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain[J]. Neurobiol Aging, 2011, 32:944-955.

Bordner KA, Kitchen RR, Carlyle B, et al. Parallel declines in cognition, motivation, and locomotion in aging mice:association with immune gene upregulation in the medial prefrontal cortex[J]. Exp Gerontol, 2011, 46:643-659.

Suzuki Y, Takagi Y, Nakamura R, et al. Ability of NMDA and non-NMDA receptor antagonists to inhibit cerebral ischemic damage in aged rats[J]. Brain Res, 2003, 964:116-120.

Won SJ, Xie L, Kim SH, et al. Influence of age on the response to fibroblast growth factor-2 treatment in a rat model of stroke[J]. Brain Res, 2006, 1123:237-244.

Popa-Wagner A, Dinca I, Yalikun S, et al. Accelerated delimitation of the infarct zone by capillary-derived nestin-positive cells in aged rats[J]. Curr Neurovasc Res, 2006, 3:3-13.

Yao H, Sadoshima S, Ooboshi H, et al. Age-related vulnerability to cerebral ischemia in spontaneously hypertensive rats[J]. Stroke, 1991, 22:1414-1418.

Cada A, de la Torre JC, Gonzalez-Lima F. Chronic cerebrovascular ischemia in aged rats:effects on brain metabolic capacity and behavior[J]. Neurobiol Aging, 2000, 21:225-233.

Lindner MD, Gribkoff VK, Donlan NA, et al. Long-lasting functional disabilities in middle-aged rats with small cerebral infarcts[J]. J Neurosci, 2003, 23:10913-10922.

Brown AW, Marlowe KJ, Bjelke B. Age effect on motor recovery in a post-acute animal stroke model[J]. Neurobiol Aging, 2003, 24:607-14.

Manwani B, Liu F, Xu Y, et al. Functional recovery in aging mice after experimental stroke[J]. Brain Behav Immun, 2011, 25:1689-1700.

Anderson MF, Blomstrand F, Blomstrand C, et al.Astrocytes and stroke:networking for survival?[J]. Neurochem Res, 2003, 28:293-305.

Astrocytes and stroke:networking for survival?[J]. Neurochem Res, 2003, 28:293-305.

Rudge JS, Silver J. Inhibition of neurite outgrowth on astroglial scars in vitro[J]. J Neurosci, 1990, 10:3594-3603.

Badan I, Buchhold B, Hamm A, et al. Accelerated glial reactivity to stroke in aged rats correlates with reduced functional recovery[J]. J Cereb Blood Flow Metab, 2003, 23:845-854.

Luo J, Daniels SB, Lennington JB, et al. The aging neurogenic subventricular zone[J]. Aging Cell, 2006, 5:139-152.

Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat:age-related decrease of neuronal progenitor proliferation[J]. J Neurosci, 1996, 16:2027-2033.

Cameron HA, McKay RD. Restoring production of hippocampal neurons in old age[J]. Nat Neurosci, 1999, 2:894-7.

Walter J, Keiner S, Witte OW, et al. Differential stroke-induced proliferative response of distinct precursor cell subpopulations in the young and aged dentate gyrus[J]. Neuroscience, 2010, 169:1279-1286.

Rao MS, Hattiangady B, Abdel-Rahman A, et al. Newly born cells in the ageing dentate gyrus display normal migration, survival and neuronal fate choice but endure retarded early maturation[J]. Eur J Neurosci, 2005, 21:464-476.

Jin K, Minami M, Xie L, et al. Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain[J]. Aging Cell, 2004, 3:373-377.

Jin K, Wang X, Xie L, et al. Evidence for stroke-induced neurogenesis in the human brain[J]. Proc Natl Acad Sci USA, 2006, 103:13198-13202.

Couillard-Despres S, Winner B, Karl C, et al. Targeted transgene expression in neuronal precursors:watching young neurons in the old brain[J]. Eur J Neurosci, 2006, 24:1535-1545.

Tang H, Wang Y, Xie L, et al. Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia[J]. Neurobiol Aging, 2009, 30:299-308.

Enwere E, Shingo T, Gregg C, et al. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination[J]. J Neurosci, 2004,24:8354-8365.

Hagihara H, Hara M, Tsunekawa K, et al. Tonic-clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine-treated mice[J]. Brain Res Mol Brain Res, 2005, 139:258-266.

Shetty AK, Hattiangady B, Shetty GA. Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus:role of astrocytes[J]. Glia, 2005, 51:173-186.

Shetty AK, Hattiangady B, Rao MS, et al. Deafferentation enhances neurogenesis in the young and middle aged hippocampus but not in the aged hippocampus[J]. Hippocampus, 2011, 21:631-646.

Ahn S, Joyner AL. In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog[J]. Nature, 2005, 437:894-897.

Goetz AK, Scheffler B, Chen HX, et al. Temporally restricted substrate interactions direct fate and specification of neural precursors derived from embryonic stem cells[J]. Proc Natl Acad Sci USA, 2006, 103:11063-11068.

Lemischka IR, Moore KA. Stem cells:interactive niches[J]. Nature, 2003, 425:778-779.

Suhonen JO, Peterson DA, Ray J, et al. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo[J]. Nature, 1996, 383:624-627.

Kearns SM, Laywell ED, Kukekov VK, et al. Extracellular matrix effects on neurosphere cell motility[J]. Exp Neurol, 2003, 182:240-244.

Xie T, Spradling AC. A niche maintaining germ line stem cells in the Drosophila ovary[J]. Science, 2000,290:328-330.

Conboy IM, Conboy MJ, Wagers AJ, et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment[J]. Nature, 2005, 433:760-764.

Gopinath SD, Rando TA. Stem cell review series:aging of the skeletal muscle stem cell niche[J]. Aging Cell, 2008, 7:590-598.

Rando TA. Stem cells, ageing and the quest for immortality[J]. Nature, 2006, 441:1080-1086.

Darsalia V, Heldmann U, Lindvall O, et al. Stroke-induced neurogenesis in aged brain[J]. Stroke, 2005, 36:1790-1795.

Macas J, Nern C, Plate KH, et al. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain[J]. J Neurosci, 2006, 26:13114-13119.

Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke[J]. Nat Med, 2002, 8:963-970.

Chen J, Zhang ZG, Li Y, et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats[J]. Circ Res, 2003, 92:692-699.

Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia[J]. J Clin Invest, 2003, 111:1843-1851.

Brivanlou AH, Gage FH, Jaenisch R, et al. Stem cells. Setting standards for human embryonic stem cells[J]. Science, 2003, 300:913-916.

Fricker RA, Carpenter MK, Winkler C, et al. Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain[J]. J Neurosci, 1999, 19:5990-6005.

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