Effects of Cortical Ischemia and Postischemic Environmental Enrichment on Hippocampal Cell Genesis and Differentiation in the Adult Rat

Abstract

Summary:The study aimed to elucidate the effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis. A cortical infarct was induced by a permanent ligation of the middle cerebral artery distal to the striatal branches in 6-month-old spontaneously hypertensive rats. Bromodeoxyuridine (BrdU) was administered as 7 consecutive daily injections starting 24 hours after surgery and animals were housed in standard or enriched environment. Four weeks after completed BrdU administration, BrdU incorporation and its co-localization with the neuronal markers NeuN and calbindin D28k, and the astrocytic marker glial fibrillary acidic protein in the granular cell layer and subgranular zone of the hippocampal dentate gyrus were determined with immunohistochemistry and were quantified stereologically. Compared with sham-operated rats, rats with cortical infarcts had a fiveto sixfold ipsilateral increase in BrdU-labeled cells. About 80% of the new cells were neurons. Differential postischemic housing did not influence significantly the total number of surviving BrdU-labeled cells or newborn neurons. However, postischemic environmental enrichment increased the ipsilateral generation of astrocytes normalizing the astrocyte-to-neuron ratio, which was significantly reduced in rats housed in standard environment postischemically.

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

“…18 Briones et al 19 further demonstrated that enriched environment did not stimulate progenitor cell proliferation after transient global brain ischemia. Interestingly, Komitova et al 20 only observed an increased dentate gliogenesis at day 35 after middle cerebral artery occlusion when the running wheel was excluded from the enriched environment. In contrast to these previous studies, we here used a model of small circumscribed cortical ischemic lesions with no direct or indirect damage to the hippocampus allowing the targeted induction of cortical infarcts in the forelimb sensorimotor cortex.…”

Adult Neurogenesis and the Ischemic Forebrain

“…Although infarct size does not appear to be affected, enrichment significantly improves performance on several measures of motor behavior and cognitive function (e.g., Ohlsson and Johansson, 1995;Komitova et al, 2002;Dahlqvist et al, 2004;Gobbo and O'Mara, 2004). Postischemic enrichment is most effective soon after stroke (Biernaskie et al, 2004), and recovery of function is further enhanced by exposure to an enriched environment both before and after stroke (Ohlsson and Johansson, 1995).…”

“…Postischemic enrichment is most effective soon after stroke (Biernaskie et al, 2004), and recovery of function is further enhanced by exposure to an enriched environment both before and after stroke (Ohlsson and Johansson, 1995). Postischemic enrichment has no apparent affect on dentate gyrus neurogenesis (Komitova et al, 2002), but an enriched environment after stroke, paired with daily rehabilitative training targeting fine digit and forelimb function, increases dendritic arborization of layer 5 pyramidal neurons within the contralateral forelimb motor cortex (Biernaskie and Corbett, 2001). Similar to the beneficial effect of environmental enrichment on stroke recovery, exercise improves functional outcome after ischemic brain injury.…”

Endothelial Proliferation and Increased Blood–Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydroxyphenyl-l-Alanine-Induced Dyskinesia

“…Under similar conditions, endothelial cells in the brain can exhibit proliferative responses (Hellsten et al, 2004;Alonso et al, 2005;Gotts and Chesselet, 2005). Moreover, an increased proliferation and maturation of precursor cells has been described in the two neurogenic regions of the adult brain (i.e., the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus) in experimental models of stroke (Arvidsson et al, 2002;Komitova et al, 2002Komitova et al, , 2005, epileptic seizures (Bengzon et al, 1997), and electroconvulsive and antidepressant therapy (Duman et al, 2001;Hellsten et al, 2002). Mitotic activity and/or cell differentiation in these two neurogenic regions is also modulated by dopaminergic deafferentation and stimulation (Hoglinger et It is presently unknown whether L-DOPA-induced dyskinesia is associated with a structural reorganization of neural circuits and their supporting glial and vascular microenvironment.…”