Different exercises can modulate the differentiation/maturation of neural stem/progenitor cells after photochemically induced focal cerebral infarction

Abstract

Introduction Exercise therapies during rehabilitation significantly promote recovery from various deficits after cerebral infarction, which is mediated by neuronal plasticity with distinct inputs. Although adult neurogenesis can also be modulated by neuronal activity before synaptogenesis, how distinct exercises contribute to the neurological reorganization of the injured cerebral cortex remains unclear. In the present study, we aimed to elucidate the effects of different exercise therapies on motor recovery and neuronal reorganization after photochemically induced focal cerebral infarction. Methods Here, we examined the effects of three different exercises—(a) forced lower‐intensity and (b) higher‐intensity treadmill exercises, and (c) voluntary exercise with wheel running—on motor recovery and adult neurogenesis in a rat model of focal cerebral infarction. Photochemically induced thrombosis (PIT) was used to generate focal infarction in rats that was mostly confined to their motor cortices. Results Beam walking tests showed that recovery after PIT‐induced cortical infarction differed in acute and chronic stages and was influenced by the type of exercise. Furthermore, forced low‐intensity training had more positive effects on functional recovery than other exercises or control. To evaluate the production of newly generated cells including de novo neurogenesis, we performed lineage analysis with BrdU labeling and immunofluorescence experiments. Lower‐intensity treadmill exercise increased the number of BrdU/NeuN colabeled cells, but not total BrdU‐retaining or BrdU/Sox2‐colabeled cells, in the peri‐infarct region of the ipsilateral cortex. In contrast, high‐intensity treadmill or voluntary exercises had the opposite effects. Conclusions These results suggest that neuronal maturation can be differently modulated by distinct exercises and that low‐intensity treadmill exercise could result in more potent generation of mature neurons. This also suggests the possibility that the generation of neural stem/progenitor cells and differentiation might be modulated by rehabilitation‐mediated neural plasticity.

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

“…The ischemic brain lesion can be easily assessed and monitored in this model by a real-time reduction in blood perfusion, which is validated by TTC-unstained brain tissue, which indicates the infarcted area. A recent preclinical study [35] in rats that used the photothrombotic stroke model demonstrated a 60-78% loss in uniform blood perfusion in the damaged area. A similar effect was observed in this study and other research by the group [17,26], and it was closely linked to sensorimotor deficit [9].…”

The potential of a combined cell‐based therapy and rehabilitation approach for stroke recovery

“…It is imperative that the increase in endogenous NSPCs after cell‐based therapy must be followed up with not only an increased training but also an appropriate rehabilitation modality that would allow the immature endogenous and exogenous cells to properly mature and effectively integrate with the host tissue. Voluntary exercise, forced physical training, and EE have all been shown to improve motor function by increasing BDNF and neurogenesis, which is one of the main driving forces underlying stroke recovery 24,25,43,61 . However, behavioral task specificity and integration need to be more widely incorporated in experimental rehabilitation strategies to achieve better functional outcomes in stroke animals 39 …”

Enriched Environment and Exercise Enhance Stem Cell Therapy for Stroke, Parkinson’s Disease, and Huntington’s Disease

“…Aerobic exercise has been shown to increase BDNF and endogenous neurogenesis ( Mang et al, 2013 ). Forced low-intensity exercise increases NPC maturation and facilitates a more robust motor recovery ( Morishita et al, 2020 ). Most importantly, both EE and stem cell transplantation increase adult neurogenesis which has been implicated as the main driving force behind recovery ( Zhan et al, 2020 ; Garthe et al, 2016 ; Tajiri et al, 2103; Singhal et al, 2014 ; van Praag et al, 1999 ) The stem cells induce neuroprotection early and influence proliferation when the rodents are still in recovery.…”