The response of the aged brain to stroke: Too much, too soon?
Popa-Wagner, Aurel ; Carmichael, Stanley Thomas ; Kokaia, Zaal LU
; Kessler, Christof
and Walker, Lary C.
(2007)
In Current Neurovascular Research
4(3).
p.216-227
- Abstract
- Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are only recently coming to light. Potential mechanisms include changes in brain plasticity-promoting factors, unregulated expression of neurotoxic factors, or differences in the generation of scar tissue that impedes the formation of new axons and blood vessels in the infarcted region. Behaviorally, aged rats are more severely impaired by stroke than are young rats, and they also show diminished functional recovery. Infarct volume does not differ significantly in young and aged animals, but critical differences are apparent in the cytological response to stroke, most notably an... (More)
- Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are only recently coming to light. Potential mechanisms include changes in brain plasticity-promoting factors, unregulated expression of neurotoxic factors, or differences in the generation of scar tissue that impedes the formation of new axons and blood vessels in the infarcted region. Behaviorally, aged rats are more severely impaired by stroke than are young rats, and they also show diminished functional recovery. Infarct volume does not differ significantly in young and aged animals, but critical differences are apparent in the cytological response to stroke, most notably an age-related acceleration of the establishment of the glial scar. The early infarct in older rats is associated with a premature accumulation of BrdU-positive microglia and astrocytes, persistence of activated oligodendrocytes, a high incidence of neuronal degeneration, and accelerated apoptosis. Regeneration-associated mechanisms in the rat brain are active thoughout life, albeit at lower levels in the aged animals. However; after stroke in aged rats, neuroepithelial marker-positive cells emanating largely from capillaries did not make a significant contribution to neurogenesis in the infarcted cortex of aged animals. Furthermore, the expression of plasticity-associated proteins, such as MAP1B, was delayed in aged rats. Tissue recovery was further delayed by the upregulation of Nogo, ephrin-A5 and MAG, which exert a powerful negative effect on axonal sprouting in the aged peri-infarct cortex, and by an age-related increase in the amount of the neurotoxic C-terminal fragment of the beta-amyloid precursor protein (beta APP) at 2 wks post-stroke. Our findings indicate that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis of this phenomenon in the aging brain could yield novel approaches to neurorestoration following stroke or head injury in the elderly. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/647816
- author
- Popa-Wagner, Aurel
; Carmichael, Stanley Thomas
; Kokaia, Zaal
LU
; Kessler, Christof
and Walker, Lary C.
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- plasticity, glial scar, astrocytes, stroke, aging, cell biology.
- in
- Current Neurovascular Research
- volume
- 4
- issue
- 3
- pages
- 216 - 227
- publisher
- Bentham Science Publishers
- external identifiers
-
- wos:000248343300009
- scopus:34547816672
- ISSN
- 1567-2026
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Restorative Neurology (0131000160)
- id
- d26e81b2-a4c6-476e-ab14-3a316b226fa6 (old id 647816)
- alternative location
- http://www.ingentaconnect.com/content/ben/cnr/2007/00000004/00000003/art00009
- date added to LUP
- 2016-04-01 12:32:07
- date last changed
- 2022-01-27 06:22:02
@article{d26e81b2-a4c6-476e-ab14-3a316b226fa6,
abstract = {{Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are only recently coming to light. Potential mechanisms include changes in brain plasticity-promoting factors, unregulated expression of neurotoxic factors, or differences in the generation of scar tissue that impedes the formation of new axons and blood vessels in the infarcted region. Behaviorally, aged rats are more severely impaired by stroke than are young rats, and they also show diminished functional recovery. Infarct volume does not differ significantly in young and aged animals, but critical differences are apparent in the cytological response to stroke, most notably an age-related acceleration of the establishment of the glial scar. The early infarct in older rats is associated with a premature accumulation of BrdU-positive microglia and astrocytes, persistence of activated oligodendrocytes, a high incidence of neuronal degeneration, and accelerated apoptosis. Regeneration-associated mechanisms in the rat brain are active thoughout life, albeit at lower levels in the aged animals. However; after stroke in aged rats, neuroepithelial marker-positive cells emanating largely from capillaries did not make a significant contribution to neurogenesis in the infarcted cortex of aged animals. Furthermore, the expression of plasticity-associated proteins, such as MAP1B, was delayed in aged rats. Tissue recovery was further delayed by the upregulation of Nogo, ephrin-A5 and MAG, which exert a powerful negative effect on axonal sprouting in the aged peri-infarct cortex, and by an age-related increase in the amount of the neurotoxic C-terminal fragment of the beta-amyloid precursor protein (beta APP) at 2 wks post-stroke. Our findings indicate that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis of this phenomenon in the aging brain could yield novel approaches to neurorestoration following stroke or head injury in the elderly.}},
author = {{Popa-Wagner, Aurel and Carmichael, Stanley Thomas and Kokaia, Zaal and Kessler, Christof and Walker, Lary C.}},
issn = {{1567-2026}},
keywords = {{plasticity; glial scar; astrocytes; stroke; aging; cell biology.}},
language = {{eng}},
number = {{3}},
pages = {{216--227}},
publisher = {{Bentham Science Publishers}},
series = {{Current Neurovascular Research}},
title = {{The response of the aged brain to stroke: Too much, too soon?}},
url = {{http://www.ingentaconnect.com/content/ben/cnr/2007/00000004/00000003/art00009}},
volume = {{4}},
year = {{2007}},
}