Early disruptions of the blood–brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats

DiNapoli, Vincent; Huber, Jason D.; Houser, Kimberly; Li, Xinlan; Rosen, Charles L.

doi:10.1016/j.neurobiolaging.2006.12.007

Cited by 152 publications

(149 citation statements)

References 41 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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“…However, the risk of stroke is increased as females age [169][170][171][172]. More severe strokes and poorer recovery was observed in elderly women and aged rodents, regardless of the sex [162][163][164][173][174][175][176]. A primary ovarian hormone, estrogen has been associated with the sex difference in ischemic stroke as treatment of estrogen in the male or ovariectomized animals reduced infarct and neuronal death following ischemia [177][178][179][180].…”

Section: Sex-associated Modulation Of Mononuclear Phagocytesmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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“…In aged rats, increased mortality rate, but similar recovery and infarct volume were found (138). Another study showed that aged rats suffer larger infarctions, reduced functional recovery and increased BBB disruption that precede observable neuronal injury (139). Aging has been shown to reduce hypoxia-induced microvascular growth in the rodent hippocampus (140).…”

Section: General Considerations When Choosing Atherosclerosis Models mentioning

confidence: 78%

Modeling Risk Factors and Confounding Effects in Stroke

2016

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Most research to date has used experimental models in rodents which fail to mimic the underlying causes of stroke in patients or the primary confounding factors. Available data indicate that factors such as atherosclerosis, hypertension, obesity, diabetes, age, and inflammation have a major influence on outcome. These findings suggest that we need to rethink the preclinical data that are required before selection of candidate interventions for clinical trials in stroke.

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Early disruptions of the blood–brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats

Cited by 152 publications

References 41 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

Microglia and Monocyte-Derived Macrophages in Stroke

Modeling Risk Factors and Confounding Effects in Stroke

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