Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats
Aging and vascular comorbidities such as hypertension comprise critical cofactors that influence how the brain responds to stroke. Ischemic stress induces neurogenesis and oligodendrogenesis in younger brains. However, it remains unclear whether these compensatory mechanisms can be maintained even u...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2016-04-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368916X690557 |
| _version_ | 1818063443858554880 |
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| author | Anna C. Liang Emiri T. Mandeville Takakuni Maki Akihiro Shindo Angel T. Som Naohiro Egawa Kanako Itoh Tsu Tshen Chuang John D. Mcneish Julie C. Holder Josephine Lok Eng H. Lo Ken Arai |
| author_facet | Anna C. Liang Emiri T. Mandeville Takakuni Maki Akihiro Shindo Angel T. Som Naohiro Egawa Kanako Itoh Tsu Tshen Chuang John D. Mcneish Julie C. Holder Josephine Lok Eng H. Lo Ken Arai |
| author_sort | Anna C. Liang |
| collection | DOAJ |
| description | Aging and vascular comorbidities such as hypertension comprise critical cofactors that influence how the brain responds to stroke. Ischemic stress induces neurogenesis and oligodendrogenesis in younger brains. However, it remains unclear whether these compensatory mechanisms can be maintained even under pathologically hypertensive and aged states. To clarify the age-related remodeling capacity after stroke under hypertensive conditions, we assessed infarct volume, behavioral outcomes, and surrogate markers of neurogenesis and oligodendrogenesis in acute and subacute phases after transient focal cerebral ischemia in 3- and 12-month-old spontaneously hypertensive rats (SHRs). Hematoxylin and eosin staining showed that 3- and 12-month-old SHRs exhibited similar infarction volumes at both 3 and 14 days after focal cerebral ischemia. However, recovery of behavioral deficits (neurological score assessment and adhesive removal test) was significantly less in 12-month-old SHRs compared to 3-month-old SHRs. Concomitantly, numbers of nestin + neural stem/progenitor cells (NSPCs) near the infarct border area or subventricular zone in 12-month-old SHRs were lower than 3-month-old SHRs at day 3. Similarly, numbers of PDGFR-α + oligodendrocyte precursor cells (OPCs) in the corpus callosum were lower in 12-month-old SHRs at day 3. Lower levels of NSPC and OPC numbers were accompanied by lower expression levels of phosphorylated CREB. By day 14 postischemia, NSPC and OPC numbers in 12-month-old SHRs recovered to similar levels as in 3-month-old SHRs, but the numbers of proliferating NSPCs (Ki-67 + nestin + cells) and proliferating OPCs (Ki-67 + PDGFR-α + cells) remained lower in the older brains even at day 14. Taken together, these findings suggest that aging may also decrease poststroke compensatory responses for neurogenesis and oligodendrogenesis even under hypertensive conditions. |
| first_indexed | 2024-12-10T14:20:11Z |
| format | Article |
| id | doaj.art-7f922247b54b4e03869f0a5b1867d9c6 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-10T14:20:11Z |
| publishDate | 2016-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-7f922247b54b4e03869f0a5b1867d9c62022-12-22T01:45:13ZengSAGE PublishingCell Transplantation0963-68971555-38922016-04-012510.3727/096368916X690557Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive RatsAnna C. Liang0Emiri T. Mandeville1Takakuni Maki2Akihiro Shindo3Angel T. Som4Naohiro Egawa5Kanako Itoh6Tsu Tshen Chuang7John D. Mcneish8Julie C. Holder9Josephine Lok10Eng H. Lo11Ken Arai12Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USARegenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Boston, MA, USARegenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Boston, MA, USARegenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Stevenage, UKNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USANeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USAAging and vascular comorbidities such as hypertension comprise critical cofactors that influence how the brain responds to stroke. Ischemic stress induces neurogenesis and oligodendrogenesis in younger brains. However, it remains unclear whether these compensatory mechanisms can be maintained even under pathologically hypertensive and aged states. To clarify the age-related remodeling capacity after stroke under hypertensive conditions, we assessed infarct volume, behavioral outcomes, and surrogate markers of neurogenesis and oligodendrogenesis in acute and subacute phases after transient focal cerebral ischemia in 3- and 12-month-old spontaneously hypertensive rats (SHRs). Hematoxylin and eosin staining showed that 3- and 12-month-old SHRs exhibited similar infarction volumes at both 3 and 14 days after focal cerebral ischemia. However, recovery of behavioral deficits (neurological score assessment and adhesive removal test) was significantly less in 12-month-old SHRs compared to 3-month-old SHRs. Concomitantly, numbers of nestin + neural stem/progenitor cells (NSPCs) near the infarct border area or subventricular zone in 12-month-old SHRs were lower than 3-month-old SHRs at day 3. Similarly, numbers of PDGFR-α + oligodendrocyte precursor cells (OPCs) in the corpus callosum were lower in 12-month-old SHRs at day 3. Lower levels of NSPC and OPC numbers were accompanied by lower expression levels of phosphorylated CREB. By day 14 postischemia, NSPC and OPC numbers in 12-month-old SHRs recovered to similar levels as in 3-month-old SHRs, but the numbers of proliferating NSPCs (Ki-67 + nestin + cells) and proliferating OPCs (Ki-67 + PDGFR-α + cells) remained lower in the older brains even at day 14. Taken together, these findings suggest that aging may also decrease poststroke compensatory responses for neurogenesis and oligodendrogenesis even under hypertensive conditions.https://doi.org/10.3727/096368916X690557 |
| spellingShingle | Anna C. Liang Emiri T. Mandeville Takakuni Maki Akihiro Shindo Angel T. Som Naohiro Egawa Kanako Itoh Tsu Tshen Chuang John D. Mcneish Julie C. Holder Josephine Lok Eng H. Lo Ken Arai Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats Cell Transplantation |
| title | Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats |
| title_full | Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats |
| title_fullStr | Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats |
| title_full_unstemmed | Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats |
| title_short | Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats |
| title_sort | effects of aging on neural stem progenitor cells and oligodendrocyte precursor cells after focal cerebral ischemia in spontaneously hypertensive rats |
| url | https://doi.org/10.3727/096368916X690557 |
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