The prevalence of cognitive dysfunction in ischemic stroke patients is abnormally high, reaching 42.4%. This issue is becoming increasingly severe among the aging population. Patients often exhibit symptoms such as memory decline, attention deficits, and reduced executive function.1,2 Therefore, early diagnosis and effective intervention are key factors to improving patient prognosis. Shepherdson et al.3 noted that “environmental enrichment for animals” involves providing essential environmental stimuli in a monotonous environment, promoting typical behavioral and psychological activities for the species, thus contributing to their mental and physical health. Numerous studies have also demonstrated4,5 that environmental enrichment serves as a rehabilitation model for rodents. Further research suggests6,7 that environmental enrichment can improve cognitive function in genetically modified Alzheimer’s rats even if β-amyloid deposits in the hippocampus remain unchanged. Therefore, it is evident that environmental enrichment can enhance cognitive abilities in animals.
This study aimed to apply nursing interventions based on environmental enrichment concepts. Cognitive function will be assessed in ischemic stroke patients using cognitive behavioral tests, while the detection of hippocampal Brain-Derived Neurotrophic Factor (BDNF) protein expression levels will be conducted using Western blot analysis, to reveal the mechanisms by which environmental enrichment interventions improve cognitive function in stroke patients.
Male SD rats (2–3 months old) were provided by the Experimental Animal Center of Xuzhou Medical University (Animal Use Permit No.: SYXK 2002-0038). The four-vessel occlusion (4-VO) model for global cerebral ischemia-reperfusion was used in this study.8 Rats were anesthetized with 20% chloral hydrate, the bilateral common carotid arteries were separated, and the vertebral arteries were electrocoagulated. On the second postoperative day, the bilateral common carotid arteries of the rats were occluded for 15 min. The sham-operated group underwent the same procedures as the experimental group, except that the bilateral common carotid arteries were not occluded. During ischemia, the rectal temperature of all animals was maintained between 36.5°C and 37.5°C, with an ear temperature of 37°C. Electroencephalogram (EEG) recording: Prior to ischemia, electrodes were implanted into the animal’s skull, positioned at the diagonal suture, and connected to a MacLab (GE HealthCare, Shanghai, China) bioelectric amplifier to record cortical wave activity. Post-ischemia, all animals were placed in a constant-temperature chamber for 3 h (30–33°C) before being returned to their cages. Animals were randomly assigned to sham, ischemia-reperfusion (1/R), and ischemia-reperfusion + environmental enrichment intervention (1/R + EEI) groups, with 10 rats per group.
Thirty male SD rats were randomly assigned to the sham, ischemia-reperfusion (1/R), and ischemiareperfusion + environmental enrichment intervention (1/R + EEI) groups, with 10 rats in each group. The sham group underwent vertebral artery electrocoagulation without common carotid artery occlusion, and was kept in a standard rearing environment for 1 week. The 1/R group underwent the 4-VO global cerebral ischemiareperfusion model and was housed in a standard rearing environment for 1 week. The 1/R + EEI group also underwent the 4-VO global cerebral ischemia-reperfusion model, but was housed in an enriched environment for 1 week.
The sham and 1/R groups were housed in an environment at a temperature of 18–22°C and relative humidity of 50%–60%, and provided with sufficient food and water, with balanced day and night cycles.
The 1/R + EEI group9 was housed in a spacious cage with a small house, ladders, hanging ropes, and wood for gnawing. In addition to water and food, peanuts and sunflower seeds were provided, and music was played for 1 h each morning and afternoon. The temperature was maintained at 18–22°C with a relative humidity of 50%–60%.
One week after ischemia-reperfusion, Western blot analysis was used to detect BDNF protein expression in the hippocampus of SD rats.10,11
During the experiment, the platform was fixed in the northwest (NW) quadrant, submerged 5 cm below the water surface. The experiment lasted for 6 d. On the first day of training (post-modeling day 8), the rats were allowed to swim freely for 1 min. From the second day onward (post-modeling day 9), each rat was tested 4 times daily, being placed in the water facing the pool wall. The average escape latency was calculated based on the arithmetic mean of the 4 trials.12–14 This study aimed to determine whether environmental enrichment improves learning ability in global ischemiareperfusion rats.
After completing the place navigation test (training day 7, post-modeling day 14), the platform was removed. Rats were placed in the water from the southeast (SE) quadrant, and their movement paths were recorded for 60 s, including time spent in the original platform quadrant, time ratio, distance ratio, average swimming speed, and the number of times they crossed the platform area.15 This study aimed to determine whether environmental enrichment enhances memory ability in global ischemiareperfusion rats.
SPSS 16.0 statistical software (IBM Corporation, Chicago, United States) was used for data analysis. All experiments were repeated three times to ensure the reliability and stability of the results. Simultaneously, this study used one-way analysis of variance (ANOVA) is used to compare the differences in cognitive function and BDNF protein expression among different treatment groups (sham surgery group, 1/R group, and 1/R + EEI group). The measurement of data within each group is independent, and the assumptions of one-way ANOVA between experimental groups are met. Measurement data were expressed as mean ± standard deviation (±s) and analyzed using one-way ANOVA. P-values <0.05 indicated statistical significance. The count data were analyzed using the chi-square test, with P-values <0.05 indicating statistical significance.
Figure 1 shows the Western blot results. Figure 1A indicates BDNF protein expression levels in the hippocampus of rats, with b-actin as the internal control. Figure 1B shows that BDNF protein levels were significantly increased in the 1/R group (P < 0.05) compared to the Sham group. Furthermore, compared to the 1/R group, BDNF protein levels were significantly increased in the 1/R + EEI group (P < 0.05). This suggests that environmental enrichment interventions can stimulate hippocampal neuron regeneration, thereby increasing BDNF protein expression.
Expression of BDNF protein content in the hippocampus of rats in different treatment groups.
Note: The sham group is set as 1. Compared with the sham group, aP < 0.05; compared with the 1/R group, bP < 0.05; Sample size, n = 10.
The place navigation test results showed that on the seventh day after ischemia-reperfusion, the 1/R group had significantly longer escape latency compared to the Sham group (P < 0.05), while the 1/R + EEI group had significantly shorter escape latency compared to the 1/R group (P < 0.05) (Figure 2).
Place navigation results for rats in different treatment groups.
The data in Table 1 indicate that the Sham group has the best cognitive and physical performance in the Morris water maze task, which is expected as they were not subjected to any ischemic injury. The 1/R group shows significant cognitive deficits due to ischemic reperfusion injury, evidenced by low platform crossings, swim speed, and time/distance ratios. The 1/R + EEI group exhibits a significant recovery in cognitive functions and physical performance, as shown by increased platform crossings and time/distance ratios compared to the 1/R group, suggesting that environmental enrichment can lead to beneficial effects on recovery from cognitive impairment following ischemic events.
Comparison of platform crossings, swim speed, time ratio, and distance ratio among different treatment groups in SD rats.
| Group | Platform crossings (60 s) | Swim speed (cm/s) | Time ratio (%) | Distance ratio (%) |
|---|---|---|---|---|
| Sham | 5.32 ± 1.76 | 40 ± 2.87 | 42.34 ± 3.23 | 42.56 ± 3.53 |
| 1/R | 2.32 ± 1.21 | 36 ± 2.01 | 24.67 ± 3.97 | 23.78 ± 2.65 |
| 1/R + EEI | 3.99 ± 1.53 | 38 ± 2.54 | 37.36 ± 3.01 | 37.84 ± 3.23 |
Ischemia-reperfusion brain injury can result in neuronal apoptosis or irreversible necrosis, affecting cognitive function.16–21 Environmental enrichment-based nursing interventions provide a lot of environmental stimuli, which may significantly enhance BDNF expression in the hippocampus. As an essential neurotrophic factor, BDNF plays a crucial role in the development and synaptic formation of the nervous system. Increased BDNF expression may promote neuronal survival and regeneration, alleviating cognitive dysfunction caused by ischemic injury.
Research has shown that hippocampal BDNF expression levels are closely related to cognition, learning, and memory functions. Environmental enrichment interventions could enhance hippocampal BDNF expression, contributing to improved cognitive abilities and memory function. BDNF may also promote the migration of neuronal precursor cells to ischemic areas, further supporting neurogenesis and functional recovery. Therefore, detecting hippocampal BDNF protein expression may effectively assess the severity of cognitive dysfunction and reveal the importance of environmental enrichment interventions in promoting cognitive recovery in ischemic stroke rats.
The innovation of this study lies in revealing the mechanism by which a nursing intervention based on environmental enrichment influences cognitive function after brain ischemia. By combining nursing interventions with basic medical testing methods, the study aims to enhance the cognitive function of ischemic stroke patients by improving external environmental stimuli to the brain. Unlike traditional drug treatments or purely cognitive training, this intervention provides diverse environmental stimuli to promote adaptive changes in the brain and improve cognitive abilities. The study also assesses cognitive function using cognitive behavioral tests and measures the expression levels of BDNF protein in the hippocampus using Western blot analysis, revealing the biological mechanism by which environmental enrichment interventions improve cognitive function. Additionally, the research highlights the crucial role of BDNF, a neurotrophic factor, in cognitive recovery, suggesting that BDNF may serve as a biological marker to assess the effectiveness of environmental enrichment interventions, providing new insights for clinical evaluation of cognitive recovery.
At the same time, our research team believes that nursing interventions based on environmental enrichment are not only applicable to ischemic stroke patients but can also be extended to patients with cognitive dysfunction from other neurological diseases, such as Alzheimer’s disease and Parkinson’s disease. Especially in different stages of the disease, this non-invasive, lowcost intervention method may yield positive effects. To maximize the intervention’s effectiveness, environmental enrichment interventions should be tailored to the patient’s cognitive status, age, and disease severity. In clinical practice, it is recommended that multidisciplinary teams, including nurses, neurologists, psychologists, and rehabilitation specialists, collaborate to comprehensively consider various intervention methods, such as environmental stimuli, cognitive training, and medication, to enhance the patient’s cognitive function and quality of life.
This study demonstrates the positive impact of environmental enrichment-based nursing interventions on cognitive function in ischemic stroke rats, providing an effective, non-invasive intervention strategy for ischemic stroke patients. This strategy supports clinical rehabilitation efforts aimed at improving patient prognosis, quality of life, and neural functional recovery. Future research could involve long-term follow-up studies to evaluate the sustained effects and safety of this intervention on cognitive recovery in patients, and explore the impact of different intervention timings based on the disease stages. Additionally, an investigation into the molecular mechanisms underlying cognitive improvement due to environmental enrichment is needed, such as genomics, transcriptomics, and other multi-omics, to identify potential molecular markers and signaling pathways. Exploring the interactions and combined effects of different neurotrophic factors (e.g., BDNF) on cognitive function will help deepen our understanding of the biological mechanisms of this intervention. As research progresses, future studies could optimize and standardize intervention protocols based on the needs of different patient populations (e.g., varying age groups, disease stages, and comorbidities), develop specific intervention guidelines, and conduct large-scale clinical validation to provide strong evidence for clinical application. Furthermore, considering differences in lifestyle and environmental stimuli across regions and cultural backgrounds, future studies could conduct cross-cultural and multi-center research to compare the effects of environmental enrichment interventions in different populations, guiding global clinical applications.