Effects of Skilled Forelimb Training on Hippocampal Neurogenesis and Spatial Learning After Focal Cortical Infarcts in the Adult Rat Brain

Abstract

Background and Purpose-Environmental stimulation consistently increases dentate neurogenesis in the adult brain and improves spatial learning. We tested the hypothesis whether specific rehabilitative training of an impaired forelimb influences these processes after focal cortical infarcts. Methods-Focal cortical infarcts were induced in the forelimb sensorimotor cortex using the photothrombosis model. One group of infarcted animals and sham-operated controls housed in standard cages received one daily session of skilled reaching training of the impaired or dominant forelimb, respectively. A second group was transferred to an enriched environment, whereas a third group remained in the standard cages without further treatment. Bromodeoxyuridine was administered from day 2 until day 6 postinfarct. Proliferation and differentiation of newborn cells was analyzed at day 10 and 42 using immunocytochemistry with neuronal and glial markers and confocal laser scanning microscopy. Spatial learning was tested in the Morris water maze between days 35 and 41. Results-After cortical infarcts in the forelimb sensorimotor cortex, environmental enrichment as well as daily reaching training of the impaired paw both increase dentate neurogenesis and improve functional performance in the Morris water maze. Nevertheless, the reaching training-induced neurogenic response was significantly greater in nonlesioned controls associated with the best spatial learning performance in the water maze. Conclusions-Skilled forelimb training effectively stimulates dentate neurogenesis and spatial learning in the infarcted and healthy brain. However, this reaching training-induced increase in neurogenesis was reduced after cortical infarcts.

Constraint-Induced Movement Therapy Enhanced Neurogenesis and Behavioral Recovery after Stroke in Adult Rats

“…A recent study showed that after cortical infarcts in the forelimb sensorimotor cortex, daily reaching training of the impaired paw significantly improved functional performance in the Morris water maze. The better spatial learning performance of the CIMT treatment group as demonstrated by the water maze data in the present study was consistent with this report (Wurm et al 2007). …”

Exercise and Environmental Enrichment as Enablers of Task-Specific Neuroplasticity and Stroke Recovery

“…Improvement in cognitive function is correlated with changes in plasticity-related genes and growth factors [33], neurogenesis [36], and endothelial cell proliferation [37]. Aerobic exercise has also been shown to induce cortical angiogenesis and improve executive function in middle-aged Cynomolgus monkeys [38].…”

“…In the studies highlighted herein, animals were housed in EE beginning within the first week poststroke, and subsequently exhibited improved spatial memory and increased markers of neuroplasticity in the ensuing weeks [33][34][35][36][37].…”

“…Poststroke exercise and EE further augment these processes in various stroke models [36,[55][56][57]. Interestingly, Komitova et al [57] reported that while poststroke EE enhanced neurogenesis in the subventricular zone, unlimited access to exercise beginning 24 h poststroke attenuated this effect.…”

Thinning, movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis

“…Another possible cellular change is the birth, migration, and maturation of new neurons (Abrahams, 2009;Keiner et al, 2009;Kuge et al, 2009;Wurm, et al, 2007;Xue et al, 2009;Zhao et al, 2009). By co-labeling cells with BrdU and NeuN, it has been suggested that neural progenitor cells might migrate from the dentate gyrus and subventricular zone into the overlying ischemic cortex.…”