eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
Current issue Archive Manuscripts accepted About the journal Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 56
Original paper

Neurogenesis in adult human brain after hemorrhage and ischemic stroke

Tomasz Stępień, Sylwia Tarka, Dominik Chutorański, Paulina Felczak, Albert Acewicz, Teresa Wierzba-Bobrowicz

Folia Neuropathol 2018; 56 (4): 293-300
Online publish date: 2018/12/31
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Adult neurogenesis includes proliferation and differentiation of progenitor cells as well as their migration and maturation. In the adult human brain, two neurogenic regions, the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of lateral ventricles, have been identified. In the dentate gyrus, three types of transcriptionally active cells and in the subventricular zone, four types of transcriptionally active cells, including GFAP-positive neural stem cells (NSCs), have been differentiated.

Material and methods
The aim of the study was to identify and compare density of neurogenic cells between two study groups of patients (7 men, 7 women, mean age 70 ± 6.03) with ischemic stroke and with hemorrhage (6 men, 2 women, mean age 64.75 ± 12.23) and the control group of patients (6 men, 2 women, mean age 64 ± 10.95) free of neuropathologic changes who died suddenly within less than 10 min.

In both groups, in the hippocampal dentate gyrus and in the subventricular zone of lateral ventricles, the presence of single GFAP-positive neural stem cells and the transcriptionally active cells labelled with phosphorylated histone H3Ser-10 (p-Histone H3Ser-10)/neural progenitor cells (NPCs), was observed. The quantitative analysis of cells with p-Histone H3Ser-10 expression in the hippocampal DG revealed significant differences between the hemorrhage and control groups (p = 0.001, test t). However, in the SVZ, it showed a statistically significant decrease in the density of transcriptionally active cells in the group of patients with ischemic stroke (p = 0.001, test t). A distinct decrease in the density of transcriptionally active cells, proportional to the length of the patients’ hospitalization, was observed.

Hypoxia belongs to pathomechanic factors responsible for ischemic stroke, which can induce neurogenesis. However, hypoxia along with ischemia and other factors implicated in ischemic stroke, such as the patient’s age or duration of ischemia can have a decisive influence on the decrease in the density of transcriptionally active cells in this pathologic process.


adult neurogenesis, ischemic stroke, p-histone H3Ser-10

Alvarez-Buylla A, García-Verdugo JM, Tramontin AD. A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2001; 2: 287-293.
Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8: 963-970.
Attardo A, Fabel K, Krebs J, Haubensak W, Huttner WB, Kempermann G. Tis21 expression marks not only populations of neurogenic precursor cells but also new postmitotic neurons in adult hippocampal neurogenesis. Cereb Cortex 2010; 20: 304-314.
Bath KG, Lee FS. Neurotrophic factor control of adult SVZ neurogenesis. Dev Neurobiol 2010; 70: 339-349.
Brown JP, Couillard-Després S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG. Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 2003; 467: 1-10.
Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC. Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction. J Cell Sci 1995; 108 (Pt 11): 3599-3609.
Chadee DN, Hendzel MJ, Tylipski CP, Allis CD, Bazett-Jones DP, Wright JA, Davie JR. Increased Ser-10 phosphorylation of histone H3 in mitogen-stimulated and oncogene-transformed mouse fibroblasts. J Biol Chem 1999; 274: 24914-2420.
Duan X, Kang E, Liu CY, Ming GL, Song H. Development of neural stem cell in the adult brain. Curr Opin Neurobiol 2008; 18: 108-115.
Eckenhoff MF, Rakic P. Radial organization of the hippocampal dentate gyrus: a Golgy, ultrastructural, and immunocitochemical analysis in the developing rhesus monkey. J Comp Neurol 1989; 223: 1-21.
Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4: 1313-1317.
Gleeson JG, Lin PT, Flanagan LA, Walsh CA. Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 1999; 23: 257-271.
Gójska-Grymajło A, Zieliński M, Gąsecki D, Kowalczyk K, Kwarciany M, Seroczyńska B, Nyka WM. CD271+, CXCR7+, CXCR4+, and CD133+ Stem/Progenitor Cells and Clinical Characteristics of Acute Ischemic Stroke Patients. Neuromolecular Med 2018; doi: 10.1007/s12017-018-8494-x.
Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP, Horvat V, Volk B, Kempermann G. Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 2010; 5: e8809.
Lee HJ, Park IH, Kim HJ, Kim SU. Human neural stem cells overexpressing glial cell line-derived neurotrophic factor in experimental cerebral hemorrhage. Gene Ther 2009; 16: 1066-1076.
Liu J, Solway K, Messing RO, Sharp FR. Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 1998; 18: 7768-7778.
Macas J, Nern C, Plate KH, Momma S. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J Neurosci 2006; 26: 13114-13119.
Mahadevan LC, Willis AC, Barratt MJ. Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell 1991; 65: 775-783.
Nagalski A, Kiersztan A. Physiology and molecular mechanism of glucocorticoid action. Postepy Hig Med Dosw (Online) 2010; 64: 133-145 [In Polish].
Ohira K, Furuta T, Hioki H, Nakamura KC, Kuramoto E, Tanaka Y, Funatsu N, Shimizu K, Oishi T, Hayashi M, Miyakawa T, Kaneko T, Nakamura S. Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells. Nat Neurosci 2010; 13: 173-179.
Okano H, Sawamoto K. Neural stem cells: involvement in adult neurogenesis and CNS repair. Philos Trans R Soc Lond B Biol Sci 2008; 363: 2111-2122.
Otero L, Zurita M, Bonilla C, Rico MA, Aguayo C, Rodriguez A, Vaquero J. Endogenous neurogenesis after intracerebral hemor­rhage. Histol Histopathol 2012; 27: 303-315.
Pluta R, Bogucka-Kocka A, Ułamek-Kozioł M, Furmaga-Jabłoń­ska W, Januszewski S, Brzozowska J, Jabłoński M, Kocki J. Neurogenesis and neuroprotection in postischemic brain neurodegeneration with Alzheimer phenotype: is there a role for curcumin? Folia Neuropathol 2015; 53: 89-99.
Rodríguez JJ, Jones VC, Tabuchi M, Allan SM, Knight EM, LaFerla FM, Oddo S, Verkhratsky A. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One 2008; 3: e2935.
Shen J, Xie L, Mao X, Zhou Y, Zhan R, Greenberg DA, Jin K. Neurogenesis after primary intracerebral hemorrhage in adult human brain. J Cereb Blood Flow Metab 2008; 28: 1460-1468.
Seri B, García-Verdugo JM, McEwen BS, Alvarez-Buylla A. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 2001; 21: 7153-7160.
Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, James D, Mayer S, Chang J, Auguste KI, Chang EF, Gutier­rez AJ, Kriegstein AR, Mathern GW, Oldham MC, Huang EJ, Garcia-Verdugo JM, Yang Z, Alvarez-Buylla A. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 2018; 555: 377-381.
Tanaka R, Yamashiro K, Mochizuki H, Cho N, Onodera M, Mizuno Y, Urabe T. Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector. Stroke 2004; 35: 1454-1459.
Tang MM, Lin WJ, Zhang JT, Zhao YW, Li YC. Exogenous FGF2 reverses depressive-like behaviors and restores the suppressed FGF2-ERK1/2 signaling and the impaired hippocampal neurogenesis induced by neuroinflammation. Brain Behav Immun 2017; 66: 322-331.
Trejo JL, Carro E, Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001; 21: 1628-1634.
Urrea C, Castellanos DA, Sagen J, Tsoulfas P, Bramlett HM, Dietrich WD. Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat. Restor Neurol Neurosci 2007; 25: 65-76.
Zhang R, Zhang L, Zhang Z, Wang Y, Lu M, Lapointe M, Chopp M. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann Neurol 2001; 50: 602-611.
Zhang R, Zhang Z, Chopp M. Function of neural stem cells in ischemic brain repair processes. J Cereb Blood Flow Metab 2016; 36: 2034-2043.
Zigova T, Pencea V, Wiegand SJ, Luskin MB. Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Mol Cell Neurosci 1998; 11: 234-245.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe