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

Abstract

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.

Microemboli alter the acute stress response and cause prolonged expression of MCP-1 in the hippocampus

“…Thereafter, and for up to 1 month, CORT responses to subsequent stressors are enhanced (De la Tremblaye et al, 2014). These findings are replicated in the current set of experiments despite the comparatively mild physiological effects of ME and the young age of the rats used in the current experiment (Merrett et al, 2010). Together, these data demonstrate that even mild cerebrovascular insults may have implications for HPA axis function up to 2 weeks following injury and suggest that further attention is warranted in this area given the high prevalence of cerebromicrovascular disease (Nemeth et al, 2014b).…”

Blockade of Mineralocorticoid and Glucocorticoid Receptors Reverses Stress-Induced Motor Impairments

“…For example, conditions such as Parkinson’s disease and stroke may become exaggerated by the experience of stress [21,22,24,81]. Blockade of MR and GR may represent a potential therapeutic target to facilitate symptomatic relief.…”

“…These observations also apply to studies of brain damage. In rat models of stroke and Parkinson’s disease, both stress and CORT can impair motor recovery [21,24] and exaggerate loss of movement [22], respectively. Notably, the motor system shows sexual dimorphism in response to stress [25].…”

Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats

“…Age is the leading nonmodifiable risk factor; thus, the elderly population is disproportionately affected by stroke. In addition to increasing risk, advanced age negatively impacts functional recovery following stroke in animal models and patients (Alaverdashvili and Whishaw, 2010; Knoflach et al, 2012; Merrett et al, 2010). Despite physical rehabilitation, many elderly stroke patients are left with a significant degree of upper limb disability (Kelly-Hayes et al, 2003).…”