Background: The society is aging in China, and the cognitive level of elderly post-stroke patients gradually declines. Face-to-face cognitive functional training is no longer sufficient. Immersive virtual reality (IVR) is a promising rehabilitation training device. In this study, we developed an IVR-based puzzle game to explore its effectiveness, feasibility, and safety in elderly stroke patients with cognitive dysfunction. Methods: A total of 30 patients with mild post-stroke cognitive impairment after stroke were randomly assigned to a control or IVR group. Patients in both groups received routine rehabilitation therapy. Patients in the control group received traditional cognitive training, and those in the IVR group received IVR-based puzzle game therapy. Before and after treatment, Montreal cognitive assessment (MOCA), trail-making test-A (TMT-A), digit symbol substitution test (DSST), digital span test (DST), verbal fluency test (VFT), and modified Barthel index (MBI) were evaluated in both groups. In addition, the IVR group was administered a self-report questionnaire to obtain feedback on user experience. Results: There was no significant difference in the baseline data between the two groups. After six weeks of treatment, the cognitive assessment scores were improved in both groups. Moreover, the IVR group showed more improvements than the control group in the DSST (Z = 2.203, p = 0.028 < 0.05, η² = 0.16); MOCA (T = 1.186, p = 0.246 > 0.05, d = 0.44), TMT-A (T = 1.791, p = 0.084 > 0.05, d = 0.65), MBI (T = 0.783, p = 0.44 > 0.05, d = 0.28), FDST (Z = 0.78, p = 0.435 > 0.05, η² = 0.02), BDST (Z = 0.347, p = 0.728 > 0.05, η² = 0.004), and VFT(Z = 1.087, p = 0.277 > 0.05, η² = 0.039) did not significantly improve. The significant difference in DSST represents an improvement in executive function and visual–spatial cognitive characteristics. The other assessment scores did not show such features. Therefore, we did not observe significant differences through this measure. According to the results of the self-report questionnaire, most of the patients were satisfied with the equipment stability and training content. Several individuals reported mild adverse reactions. Conclusions: This pilot study suggests that IVR-based puzzle games are a promising approach to improve post-stroke cognitive function, especially executive cognitive function, and visual–spatial attention in older adults.

Exercise training is a neuroprotective strategy in cerebral ischemic injury, but the underlying mechanisms are not yet clear. In the present study, we investigated the effects of treadmill exercise pretreatment on the expression of mitochondrial dynamic proteins. We examined the expression of OPA1/DLP1/MFF/Mfn1/Mfn2, which regulatesmitochondrial fusion and fission, and cytochrome C oxidase subunits (COX subunits), which regulatemitochondrial functions, after middle cerebral artery occlusion (MCAO) in rats. T2-weighted magnetic resonance imaging (MRI) was evaluated as indices of brain edema after ischemia as well. Treadmill training pretreatment increased the expression levels of OPA1 and COXII/III/IV and alleviated brain edema, indicating that exercise pretreatment provided neuroprotection in cerebral ischemic injury via the regulation of mitochondrial dynamics and functions.

Stroke is one of the leading causes of death and the primary cause of acquired disability worldwide. Many stroke survivors have difficulty using their upper limbs, which have important functional roles in the performance of daily life activities. Consequently, the independence and quality of life of most stroke patients are reduced. Robot‐assisted therapy is an effective intervention for improving the upper limb function of individuals with stroke. Human‐robot collaborative interaction force control technology is critical for improving the flexibility and followability of the robot’s motion, thereby improving rehabilitation training outcomes. However, there are few reports on the effect of robot‐assisted rehabilitative training on upper limb function. We applied this technology using a robot to assist patients with task‐oriented training. Posttreatment changes in Fugl‐Meyer and modified Barthel index (MBI) scores were assessed to determine whether this technology could improve the upper limb function of stroke patients. One healthy adult and five stroke patients, respectively, participated in functional and clinical experiments. The MBI and Fugl‐Meyer scores of the five patients in the clinical experiments showed significant improvements after the intervention. The experimental results indicate that human‐robot collaborative interaction force control technology is valuable for improving robots’ properties and patients’ recovery. This trial was registered in the Chinese clinical trial registry (ChiCTR2000038676).

Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC)-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1) protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.

Understanding the patterns of brain glucose metabolism and connectivity in hypoxic-ischemic encephalopathy (HIE) patients with prolonged disorders of consciousness (DOC) may be of positive significance to the accurate assessment of consciousness and the optimization of neuromodulation strategy. We retrospectively analyzed the brain glucose metabolism pattern and its correlation with clinical Coma Recovery Scale-Revised (CRS-R) score in six HIE patients with prolonged DOC who had undergone ¹⁸F-deoxyglucose brain positron emission tomography scanning (FDG-PET). We also compared the differences in global metabolic connectivity patterns and the characteristics of several brain networks between HIE patients and healthy controls (HC). The metabolism of multiple brain regions decreased significantly in HIE patients, and the degree of local metabolic preservation was correlated with CRS-R score. The internal metabolic connectivity of occipital lobe and limbic system in HIE patients decreased, and their metabolic connectivity with frontal lobe, parietal lobe and temporal lobe also decreased. The metabolic connectivity patterns of default mode network, dorsal attention network, salience network, executive control network and subcortex network of HIE also changed compared with HC. The present study suggested that pattern of cerebral glucose metabolism and network connectivity of HIE patients with prolonged DOC were significantly different from those of healthy people.

Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P<0.0001, AUC=1.000), and furthermore could effectively distinguish MCS from UWS (P=0.037, AUC=0.821, sensitivity: 85.7 %, specificity: 75.0 %). Particularly in the subgroup of DOC patients survived global hypoxic-ischemic brain injury, DOCRP expression exhibited even better discriminatory power between MCS and UWS (P=0.046, AUC=1.000). DOCRP might serve as an objective biomarker in distinguishing between UWS and MCS, especially in patients survived global hypoxic-ischemic brain injury. ChiCTR2300073717 (Chinese clinical trial registry site, http://www.chictr.org).