Accelerated Glial Reactivity to Stroke in Aged Rats Correlates with Reduced Functional Recovery

Badan, Irina; Buchhold, B; Hamm, Alfons O.; Gratz, Matthias; Walker, Lary C.; Platt, Daniel H.; Kessler, C.; Popa‐Wagner, Aurel

doi:10.1097/01.wcb.0000071883.63724.a7

Cited by 204 publications

(202 citation statements)

References 46 publications

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“…Aged rats with ischemic insult were shown to develop larger infarct volumes [39][40][41] or greater tissue distortion than young animals [28]. These observations might be related to increased necrosis, damaged blood-brain barrier, and enhanced microglial activation that were reported for aged animals [39][40][41][42].…”

Section: Discussionmentioning

confidence: 81%

Synergistic effects of age and stress in a rodent model of stroke

Merrett

Kirkland

Metz

2010

Behavioural Brain Research

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Ageing and stress represent critical influences on stroke risk and outcome. These variables are intricately linked, as ageing is frequently associated with gradual dysregulation of the hypothalamic-pituitary-adrenal axis. This study determined the effects of stress on motor function in aged rats, and explored possible interactions of age and stress on motor recovery following stroke in a rat model. Young adult (4 months) and aged (18 months) male Wistar rats were tested in skilled and non-skilled movement before and after focal ischemia in motor cortex. One group of each age received restraint stress starting seven days pre-lesion until three weeks post-lesion. Aged rats were less mobile and stress further diminished their overall exploratory activity. Aged rats were also less proficient in motor skill acquisition and slower to improve after lesion. Stress diminished post-lesion improvement and prevented recovery of endpoint measures. The larger functional loss in aged rats vs. young rats was accompanied by greater damage of cortical tissue and persistent elevations in corticosterone levels. The behavioural and physiological measures suggest limited ability of aged animals to adapt to chronic stress. These findings show that age or stress alone can modulate motor performance but may have greater influence by synergistically affecting stroke recovery.

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Section: Discussionmentioning

confidence: 81%

Synergistic effects of age and stress in a rodent model of stroke

Merrett

Kirkland

Metz

2010

Behavioural Brain Research

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“…Interestingly, it has been reported that aged rats have accelerated glial reactivity in response to cerebral ischemia, which coincides with stagnation of functional recovery. 25 Thus, the worsening of neurological deficits in Tg huS100B mice after pMCAO may represent an event caused by inappropriately accelerated glial responses.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis After Permanent Focal Ischemia

Mori

Tan

Arendash

et al. 2008

Stroke

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Background and Purpose-We have previously demonstrated that augmented and prolonged activation of astrocytes detrimentally influences both the subacute and chronic phases of cerebral ischemia. Furthermore, we have suggested that the astrocyte-derived protein S100B may be important in these pathogenic events. However, the causal relationship between S100B and exacerbation of brain damage in vivo remains to be elucidated. Methods-Using transgenic mice overexpressing human S100B (Tg huS100B mice), we examined whether S100B plays a cardinal role in aggravation of brain damage after permanent middle cerebral artery occlusion (pMCAO). Results-Tg huS100B mice had significantly larger infarct volumes and worse neurological deficits at any time point examined after pMCAO as compared with CD-1 background strain-matched control mice. Infarct volumes in Tg huS100B mice were significantly increased from 1 to 3 and 5 days after pMCAO (delayed infarct expansion), whereas those in control mice were not significantly altered. S100, glial fibrillary acidic protein, and Iba1 burdens in the periinfarct area were significantly increased through to 7 days after pMCAO in Tg huS100B mice, whereas those in control mice reached a plateau at 3 days after pMCAO. Conclusions-These results provide genetic evidence that overexpression of human S100B acts to exacerbate brain damage and periinfarct reactive gliosis (astrocytosis and microgliosis) during the subacute phase of pMCAO. (Stroke.

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“…To date, however, experimental studies of radiation-induced inflammation, brain injury and cognitive dysfunction have been conducted almost exclusively in animals a few weeks to a few months old, young ages that do not reflect important neurobiological changes that occur with normal aging, such as decreased proliferation and neurogenesis (15)(16)(17)(18), increased microglial activation (19,20) and expression of pro-inflammatory cytokines (20)(21)(22). Experimental studies of stroke, traumatic brain injury, exogenous cytokine administration, and axotomy support the hypothesis that aging impacts the intensity and duration of brain inflammation and glial activation following challenges (23)(24)(25)(26)(27)(28). Moreover, evidence that old age impacts the duration of some radiation-induced cognitive deficits in rodents (29,30) suggests greater radiation-induced injury in older rats.…”

Section: Introductionmentioning

confidence: 99%

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

Schindler¹,

Forbes²,

Robbins³

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To assess the impact of aging on the radiation response in the adult rat brain.Methods and Materials-Male rats 8, 18, or 28 months of age received a single 10Gy dose of whole brain irradiation (WBI). The hippocampal dentate gyrus (DG) was analyzed one and ten weeks later for sensitive neurobiological markers associated with radiation-induced damage: changes in the density of proliferating cells, immature neurons, total microglia, and activated microglia.Results-A significant reduction in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased following WBI in young rats but not in old rats. Total microglial number decreased following WBI at all ages but microglial activation increased markedly, particularly in older animals.Conclusions-Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in the number of immature neurons following WBI but have a greater inflammatory response. The latter may play an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

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Accelerated Glial Reactivity to Stroke in Aged Rats Correlates with Reduced Functional Recovery

Cited by 204 publications

References 46 publications

Synergistic effects of age and stress in a rodent model of stroke

Synergistic effects of age and stress in a rodent model of stroke

Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis After Permanent Focal Ischemia

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

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