Age effect on motor recovery in a post-acute animal stroke model

doi:10.1016/S0197-4580(02)00129-X

Neurobiology of Aging

Volume 24, Issue 4, July–August 2003, Pages 607-614

https://doi.org/10.1016/S0197-4580(02)00129-X Get rights and content

Abstract

Male Fischer 344 rats aged 3, 6, 12, 18 and 24 months were trained to walk on a narrow beam, then lesioned in the right hindlimb sensorimotor cortex by photothrombosis. Motor performance was measured daily for 60 days using a 7-point rating scale from which deficit scores were calculated. Tissue analysis included lesion volume measurement after Nissl staining. Animals aged 3 and 6 months fully recovered by day 10 and 31, respectively. Animals aged 18 months acquired significant neurological impairment that persisted greater than 60 days. Deficit scores were significantly greater than in groups aged 12, 6 and 3 months. Degenerative morbidity and mortality confounded behavioral study of animals aged 24 months. The duration of neurological impairment after photochemical sensorimotor cortex lesion increased with age. Animals aged 18 months at lesion acquired the greatest chronic impairment. This aged post-acute animal model is clinically relevant to stroke rehabilitation.

Introduction

Experimental models of cerebrovascular disease have largely utilized invasive surgical lesion methods and young animals. Treatment has focused on acute intervention to limit the extent of tissue injury, with histological and behavioral analysis occurring early in the recovery phase. There is no established model of chronic neurological impairment after focal cortical lesion, a condition common to an increasing number of stroke survivors. We developed an animal model of stroke utilizing the non-invasive photochemical lesion technique of Watson et al. [87] in young albino rats aged 3 months [3]. Using magnetic resonance imaging (MRI) and non-aversive behavioral methods to study recovery of locomotor function, we showed that the acute MRI lesion signature in this model is consistent with human stroke in the subacute to chronic phase [12], [38]. These animals aged 3 months recovered locomotor function within 10 days. We hypothesize that the duration of neurological impairment after focal cortical lesion will increase with age, providing an experimental model of chronic neurological impairment such as that experienced by the majority of stroke survivors.

Section snippets

Materials and methods

This protocol was approved by the Institutional Animal Care and Use Committee of the Mayo Foundation for Education and Research. A total of 133 male F344 rats (National Institute on Aging, Harlan Sprague–Dawley) aged 3, 6, 12, 18 and 24 months were housed 3–4 per cage under standard conditions, in a cubicle isolated from females or other species, with free access to food and water and an automated 12-h light cycle. Behavioral training and testing occurred between the hours of 6 a.m. and 1 p.m.

Results

Of the 133 animals used for this study, 49 were excluded. Thirty-four animals were unsuccessfully trained due to an age-dependent behavior of continual static beam sitting (18 animals aged 3 months; 4 animals aged 6 months; 7 animals aged 12 months; 3 animals aged 18 months; 2 animals aged 24 months). An additional 7 animals aged 24 months were unable to be trained due to disease, death, tumor or pre-existing impairment. Eight trained and lesioned animals were eliminated due to death prior to

Discussion

Physical and cognitive performance generally diminishes with age in humans, and discovering the neurobiological correlates to these behavioral changes is a point of intense research focus. The previously held view of a senescent decrease in neuron number [4], [5], [13], [42], [45], [46], [85] is changing to one of relative neuronal preservation [29], [41], [47], [53], [82], though considerable individual variability is a consistent finding throughout the literature [28], [29], [30], [78].

Acknowledgements

The authors gratefully acknowledge Dr. Fredric Meyer, Mr. Robert Anderson, Ms. Heidi Martin, the Department of Neurologic Surgery, Mayo Clinic Rochester, and Mayo Foundation for their support of this work.

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Age effect on motor recovery in a post-acute animal stroke model

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Brain Res.

Neurobiol. Aging

Neuroscience

Mech. Ageing Dev.

Neurobiol. Aging

Mech. Ageing Dev.

Neurobiol. Aging

Progr. Neurobiol.

Neurobiol. Aging

Brain Res.

Neurobiol. Aging

Neurobiol. Aging

Mech. Ageing Dev.

Neurobiol. Aging

Mech. Ageing Dev.

J. Neurol. Sci.

Neurobiol. Aging

Neurobiol. Aging

Neurosci. Lett.

Neurobiol. Aging

Neurobiol. Aging

Neurobiol. Aging

Brain Res.

Neurosci. Lett.

Int. J. Dev. Neurosci.

Neurobiol. Aging

Lancet

Brain Res.

Age and hemisphere effects on dendritic structure

Brain

Neurochemical changes in the hippocampus of the brown Norway rat during aging

Neurobiol. Aging

Beam walking without aversive stimuli as a tool to record recovery after photochemical induced unilateral lesion of the sensory-motor cortex. Training effect contra d-amphetamine treatment [abstract]

Abstr. Soc. Neurosci.

Organization of the cerebral cortex III. A study of aging in the human cerebral cortex

J. Comp. Neurol.

Neocortical synapse density and Braak stage in the Lewy body variant of Alzheimer disease: a comparison with classic Alzheimer disease and normal aging

J. Neuropathol. Exp. Neurol.

Dying-back of Purkinje cell dendrites with synapse loss in aging rats

J. Neurocytol.

Synaptic plasticity and functional stabilization in the hippocampal formation: possible role in Alzheimer’s disease

Adv. Neurol.

Experimental stroke and neuroprotection in the aging rat brain

Stroke

Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex

Eur. J. Neurosci.

The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age

J. Cerebral Blood Flow Metab.

Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury

Science

Embolic stroke in aged rats

Stroke

Changes in somatodendritic but not terminal dopamine regulation in aged rhesus monkeys

J. Neurochem.

EM study of the numbers of cortical synapses in the brains of ageing people and people with Alzheimer-type dementia

Acta Neuropathologica