Differential Effects of Physical and Social Enriched Environment on Angiogenesis in Male Rats After Cerebral Ischemia/Reperfusion Injury

Abstract

Different housing conditions, including housing space and the physiological and social environment, may affect rodent behavior. Here, we examined the effects of different housing conditions on post-stroke angiogenesis and functional recovery to clarify the ambiguity about environmental enrichment and its components. Male rats in the model groups underwent right middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO rats were divided into four groups: the physical enrichment (PE) group, the social enrichment (SE) group, the combined physical and social enrichment (PSE) group and the ischemia/reperfusion + standard conditioning (IS) group. The rats in the sham surgery (SS) group were housed under standard conditions. In a set of behavioral tests, including the modified Neurological Severity Score (mNSS), rotarod test, and adhesive removal test, we demonstrated that the animals in the enriched condition groups exhibited significantly improved neurological functions compared to those in the standard housing group. Smaller infarction volumes were observed in the animals of the PSE group by MRI detection. The enriched conditions increased the microvessel density (MVD) in the ischemic boundary zone, as revealed by CD31 immunofluorescent staining. The immunochemical and q-PCR results further showed that environmental enrichment increased the expression levels of angiogenic factors after ischemia/reperfusion injury. Our data suggest that all three enrichment conditions promoted enhanced angiogenesis and functional recovery after ischemia/reperfusion injury compared to the standard housing, while only exposure to the combination of both physical and social enrichment yielded optimal benefits.

Enriched environment promotes post-stroke angiogenesis through astrocytic interleukin-17A

“…Rats were tested under the accelerating rotor mode with acceleration from 5 to 40 rpm for in 300 s. The length of time that the animal remained on the rod was noted by an investigator who was blinded to the experimental groups. The final score for statistical analysis was expressed as the mean time that a rat could remain on the rod over two trials ( Zhang et al, 2021 ).…”

“…An enriched environment (EE) is a non-invasive approach comprising voluntary physical activity, social interaction, introduction to new stimuli (by equipping the environment with different toys), and providing a larger space than a standard cage. EE has been shown to play important roles in promoting brain plasticity, angiogenesis, and neurogenesis, ultimately exerting a beneficial influence on brain function and recovery after injury ( Kühn et al, 2017 ; Zhang et al, 2018 , 2021 ). Our previous studies on this subject have proved that exposure to EE following ischemic stroke may lead to astrocyte proliferation and angiogenesis along with trophic factor production, ultimately contributing to functional recovery ( Chen X. et al, 2017 ; Zhang et al, 2017 ).…”

The role of enriched environment in neural development and repair

“…A significant increase in angiogenesis specific marker CD31 was observed in the cortical area around infarction after EE, and the neurological function was positively correlated with angiogenesis (Yu et al, 2014 ). When sub-components were isolated to dissect their contribution to the total effect of EE by rearing animals either by stimulating physical exercise, or under social enrichment alone, the results showed that complete EE had a more significant benefit than single sub-components on microvessel density, as manifested by elevated expression of angiopoietin 1, VEGF, and CD31 (Zhang et al, 2021 ). The mechanism underlying angiogenesis may be mediated by hepatocyte growth factor, a blood-derived factor, which was elevated by EE in cortex and serum after middle cerebral artery occlusion (MCAO).…”

Combined robot motor assistance with neural circuit-based virtual reality (NeuCir-VR) lower extremity rehabilitation training in patients after stroke: a study protocol for a single-centre randomised controlled trial

“…24 Besides, enriched environment treatment may provide neuroprotection 25 and enhance angiogenesis to promote functional recovery after stroke. 26 Furthermore, multiple studies have shown that reward positively affects motor adaptation, [27][28][29] influencing neural activity related to motor preparation and execution. 30 Actually, a previous study has found that multiple rewards can enhance motor recovery and adaptive brain plasticity.…”

“…A previous study found that enriched environmental training can activate brain-derived neurotrophic factor protein expression, improve neurological function and enhance resilience to cerebral ischaemia 24. Besides, enriched environment treatment may provide neuroprotection25 and enhance angiogenesis to promote functional recovery after stroke 26. Furthermore, multiple studies have shown that reward positively affects motor adaptation,27–29 influencing neural activity related to motor preparation and execution 30.…”