Introduction: Growing evidence has brought stem cell therapy to the forefront as new promising approaches towards stroke treatment. Of all candidate seeding cells, adipose-derived stem cells (ADSCs) are considered as one of the most appropriate for stroke treatment. However, previous experimental data could not reach to an agreement on the efficacy of ADSC transplantation for treating stroke in vivo as well as its mechanism which hinders their further clinical translational application. Methods: To explore their in vivo mechanism of hADSC administration on neurological injury, hADSC were labeled with Enhanced Green Fluorescence Protein expressing FG12 lentivirus and injected into MCAO mouse infarct area by in situ way. Neurological function was evaluated by Rogers Scaling System and their spatial learning and memory was determined by Morris Test. 2,3,5-triphenyltetrazolium chloride was carried out to compare the infarct area among groups. Histoimmunostaining was used to track the injected hADSCs for their in vivo migration, transdifferentiation and integration with the endogenous neuronal circuitry. To better address the underlying rescuing mechanism, qRT-PCR was performed on neural markers of MBP, MAP2, GFAP, microglia marker of Iba1. Results: It was found that hADSCs could promote both spatial learning and memory of MCAO mice. Co-localization of GFP and MAP2 were found in the whole cortex with significantly (P<0.01) higher percentage at the contralateral cortex compared with the ipsilateral cortex. Low percentage of GFP and GFAP co-localized cells were found at whole cortex. Meanwhile, Iba1⁺ microglia and GFAP⁺ astrocyte cells were significantly (P<0.05) suppressed by hADSC injection. Conclusions: hADSCs could transdifferentiate into neuron like cells (MAP2⁺) in vivo and probably used as seeding cells for replacement based stem cell therapy of stroke. Also, significant immunomodulation was found. Meanwhile hADSCs could significantly protect the endogenous neuron survival. This study demonstrated that hADSC intervention with MCAO mice could apparently ameliorate stroke symptoms by direct cell replacement, enhanced immnunosuppression and increasing the viability of endogenous neurons.

Objective: To investigate whether the “obesity paradox” in acute ischemic stroke (AIS) is a masking effect of metabolic lipid reserves. We evaluated the independent and opposing associations of body weight status and admission triglycerides (TG) with 90-day functional outcomes to distinguish the structural burden of obesity from metabolic health. Methods: This dual-center retrospective cohort study included 571 consecutive AIS patients recruited between 2019 and 2024. Patients were categorized into normal-weight (NW, n = 245; BMI 18.5–23.9 kg/m ² ) and overweight-or-obesity (OW, n = 326; BMI ≥ 24.0 kg/m ² ) groups. The primary endpoint was an excellent functional outcome [modified Rankin Scale (mRS) 0–1] at 90 days. Multivariable logistic regression and inverse probability weighting (IPW) were employed to isolate the independent effects of weight status and TG levels. Results: At 90 days, the proportion of patients achieving an excellent outcome was significantly higher in the NW group than in the OW group (60.4% vs. 50.6%; p = 0.020). In univariable analysis, patients who achieved an excellent outcome (mRS 0–1) had significantly higher admission TG levels than those who did not [median 1.33 (IQR 0.97–1.92) vs. 1.13 (IQR 0.90–1.48) mmol/L; p &lt; 0.001]. After adjusting for comprehensive confounders including age, NIHSS, and other lipid profiles, overweight-or-obesity was independently associated with lower odds of an excellent outcome (adjusted OR = 0.611, 95% CI: 0.394–0.945; p = 0.027). Conversely, higher admission TG levels were significantly associated with better recovery (adjusted OR = 1.405 per 1 mmol/L increase, 95% CI: 1.057–1.867; p = 0.019). These opposing associations remained robust in IPW sensitivity analyses. Conclusion: The “obesity paradox” in AIS appears to be a masking effect driven by TG reserves. Once disentangled from metabolic benefits, overweight and obesity emerge as independent risk factors for poorer recovery. These findings support a phase-specific metabolic management strategy: mitigating the physical and systemic burdens of obesity while ensuring sufficient TG levels within the physiological range to support neural repair during the acute window.