Small Vessel Disease and Cerebral Infarct Healing InErvation Via Limb Distant Adaptation

the Role and Mechanism of Distant Ischemic Adaptation in Improving Cognitive Impairment in Cerebral Infarction and Cerebral Small Vessel Disease

Cerebral infarction (ischemic stroke) and cerebral small vessel disease (CSVD) represent major global causes of disability, cognitive decline, and mortality. Despite advances in reperfusion therapies, many patients experience residual neurological deficits and remain at high risk for recurrent stroke and vascular dementia. Effective adjunctive treatments that are safe, accessible, and capable of improving long-term outcomes are urgently needed.

Distant ischemic adaptation (also known as remote ischemic conditioning, RIC) is a non-invasive, safe, and cost-effective intervention that induces endogenous protection against ischemic injury by applying brief, intermittent ischemia to a remote limb. While several large-scale clinical trials (e.g., RICAMIS, RECAST) have demonstrated promising neuroprotective effects of RIC in acute ischemic stroke, results remain inconsistent across studies, particularly in patients with CSVD. Key challenges include the lack of standardized RIC protocols and the absence of specific biomarkers to predict treatment response and elucidate underlying mechanisms.

To address these gaps, this study aims to identify potential effector proteins and specific biomarkers that mediate the therapeutic effects of RIC in patients with cerebral infarction and CSVD. By collecting and analyzing serum samples from RIC-treated patients and controls, we seek to uncover molecular mechanisms underlying RIC-induced neuroprotection and cognitive preservation. The findings may establish a theoretical foundation for optimizing RIC therapy, provide novel drug targets, and ultimately improve clinical outcomes for patients suffering from ischemic stroke and small vessel disease.

Inclusion Criteria:

• Aged between 50 and 65 years.
• Definite diagnosis of cerebral infarction or cerebral small vessel disease-related cerebral infarction confirmed by brain MRI or other imaging examinations.
• Ability to complete the 3-month follow-up and RIC intervention (for the experimental group).
• Few underlying comorbidities, limited to hypertension and hyperlipidemia; clear consciousness with the ability to provide informed consent.
• Modified Rankin Scale (mRS) score < 2, with no severe cognitive impairment as assessed by the Montreal Cognitive Assessment (MoCA).
• Enrolled within 48 hours after the onset of stroke symptoms (i.e., from the time the patient was last known to be well, during the acute phase).

Exclusion Criteria:

• Complicated with diabetes mellitus, smoking history, or other metabolic disorders.
• Complicated with other types of stroke (e.g., cardioembolic stroke, large artery atherosclerotic stroke, etc.).
• Presence of severe cognitive impairment, depression, or other psychiatric or neurological disorders.