Background and purpose: The age-related decline in plasticity of the brain may be one factor underlying the poor functional recovery after stroke. In the present work we tested the hypothesis that the attenuation of neural plasticity could be the result of an age-related REDUCTION in the upregulation of factors promoting brain plasticity (microtubule-associated protein 1B [MAP1B], beta-amyloid precursor protein [betaAPP]), and an age-related INCREASE in glial reactivity and the accumulation of Abeta, a proteolytic cleavage product of betaAPP with neurotoxic properties.
Methods: Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. The functional outcome was assessed in neurobehavioral tests 3, 7, 14 and 28 days after surgery. At the indicated time points, brains were removed and immunostained for glial cells. Abeta, as well as the markers of brain plasticity, betaAPP and MAP1B.
Results: Histologically, in young rats there was a gradual activation of both microglia and astrocytes that peaked by days 14-28 with the formation of a glial scar. In contrast, aged rats showed an accelerated astrocytic and microglial reaction that peaked in the first week after stroke. The expression patterns of a growth-associated phenotype of betaAPP as well as with MAP1B accumulation in varicosities along axons in cortical areas affected by stroke peaked between days 14 and 28 in young animals. In aged rats their expression was both delayed (28 days) and reduced. In addition the carboxy terminal fragment of betaAPP steadily accumulated over time and reached a maximum by day 14 in aged rats as compared to 28 days in young rats.
Conclusions: These results suggest that a temporally anomalous gliotic reaction to cerebral ischemia in aged rats in conjunction with a late and limited upregulation of neuronal plasticity proteins as well as a diminished neurogenesis potential lead to the prevalence of scar tissue that impedes functional recovery from stroke.
Copyright 2003 S. Karger AG, Basel