Effects of enriched environment on hippocampal neuronal cell death and neurogenesis in rat global ischemia.

Enriched environments reportedly show neuroprotective effects. Here, we evaluated the effect of an enriched environment prior to cerebral ischemia on neuronal cell death and neurogenesis in rats. Male SD rats were housed under standard conditions (SC) or in an enriched environment (EE), then subjected to global ischemia. The Y-maze test and novel object cognition test were used to evaluate cognitive function before and after ischemia. At 7 days post-ischemia, we evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding protein (phospho-CREB) was also evaluated immunohistochemically. The EE + ischemia group showed a significant decrease of cell death post-ischemia compared with the SC + ischemia group. There was no difference in neurogenesis post-ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed a significant increase of performance before and after ischemia compared with the SC + ischemia group. Phospho-CREB-positive cells were significantly increased post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed hippocampal cell death due to global ischemia. Additionally, enhancement of cognitive function before and after ischemia and prevention of cognitive impairment associated with ischemia were observed compared with the controls (rats housed in SC without ischemia). The CREB pathway may play an important role in protection of cognitive ability.

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS.

Acute stress exposure preceding global brain ischemia accelerates decreased doublecortin expression in the rat retrosplenial cortex.

BACKGROUND: Psychological distress is a risk factor of stroke in humans and worsens the behavioral and neurological outcomes. In rats, acute stress exposure preceding ischemic events attenuates learning and memory. The retrosplenial cortex (RS) plays an important role in these functions, and global brain ischemia (GBI) or acute stress exposure can induce a decrease in expression of the immature neuronal marker, doublecortin (DCX), in the RS. However, little is known about the DCX expression in the RS after stress exposure prior to GBI. METHODS: Eighteen male Sprague-Dawley rats were used. Acute stress exposure was applied as the forced swim paradigm and GBI was induced by bilateral common carotid arterial occlusion for 10 min. The rats were divided into three groups: GBI model preconditioned by stress (n = 6, Group P), GBI model preconditioned by non-stress (n = 6, Group G), and controls (n = 6, Group C). We performed immunohistochemistry to observe and analyze the DCX-expressing cells and Fluoro-Jade B (FJB) staining to detect cell death in the RS after GBI in each group. RESULTS: The total number of DCX-expressing cells was 1,032, 1,219, and 1,904 in Group P, Group G, and Group C, respectively. The mean number of DCX-expressing cells per unit area was significantly lower in Group P and Group G than in Group C (P < 0.001). Moreover, the number was significantly lower in Group P than in Group G (P < 0.05). In each group, no FJB positive cells were observed. CONCLUSION: DCX plays an important role in various cytoskeletal changes. Preconditioning by acute stress exposure accelerated the decrease in DCX expression in the RS after GBI.

DCX-expressing neurons decrease in the retrosplenial cortex after global brain ischemia.

Many studies have demonstrated cognitive function disorders including space learning disorders after global brain ischemia (GBI). Previous research on space perception and learning has indicated that the retrosplenial cortex (RS) is strongly involved. We performed immunostaining with doublecortin (DCX) for neurons with plasticity potential in the RS and investigated the neuronal numbers to assess the changes of plasticity in the RS following GBI. We employed male Sprague-Dawley rats and carried out bilateral carotid arterial occlusion for 10 min as a GBI model (control, n = 5; GBI model, n = 5). We counted the right and left hemispheres separately on two serial sections, for a total of four regions per animal to examine the differences in expression related to GBI. Additionally, we performed Fluoro-Jade B (FJB) staining to investigate the cause of any DCX-expressing neuron decrease. The total number of DCX-expressing neurons was 1,652 and 912 in the controls and GBI model, respectively. The mean number of DCX-expressing neurons per unit area was significantly lower in the GBI model than in the controls. FJB positive neurons were not found in the RS, while many were present in the -hippocampus CA1 after GBI. The decrease of DCX-expressing neurons in the RS indicated a plasticity decrease following GBI. The lack of FJB positive neurons in the RS after GBI suggested that the decrease of DCX-expressing neurons in the RS was not due to neuronal cell death in contrast to the hippocampus CA1, while the FJB positive neurons in the hippocampus indicated a delayed neuronal cell death as observed in many previous studies.