Stroke and its consequences

Stroke is the third most common cause of death and the leading cause of disability in adults. Ischaemic stroke (about 85% of cases) — occlusion of a cerebral artery by thrombus or embolus — is distinguished from haemorrhagic stroke — vessel rupture with intracerebral haemorrhage. After the acute period (4–6 weeks) a scar zone forms and neurological deficits persist: hemiparesis, speech disorders (aphasia), cognitive impairment, coordination problems. Standard rehabilitation produces its greatest effect within the first 3–6 months, after which the pace of recovery sharply declines. Cell therapy is considered in the subacute (1–3 months post-stroke) and chronic (3–12+ months) periods as a means of extending the rehabilitation window and reactivating the brain's intrinsic recovery resources.

According to WHO, approximately 13 million new strokes are recorded worldwide each year, with around 5.5 million deaths attributable to them. In Russia about 450,000 cases occur annually; 30–35% of patients die within the first year, and 60–70% of survivors carry long-term functional limitations. Major modifiable risk factors are arterial hypertension, atrial fibrillation, diabetes mellitus, dyslipidaemia, smoking, abdominal obesity, and physical inactivity. Non-modifiable factors include age, male sex (until 75 years), heredity, and presence of thrombophilic states. Secondary prevention is the obligatory background of any rehabilitation, including cell-based therapy: without blood-pressure control, antiplatelet therapy in ischaemic stroke, or anticoagulation in atrial fibrillation, any regenerative method works against a continuous risk of recurrence.

The pathophysiology of ischaemic stroke unfolds as a cascade lasting from minutes to weeks. Within seconds of occlusion, neurons in the core lose ATP, membranes depolarise, glutamate is massively released, and calcium excitotoxicity ensues; mitochondria fail and apoptotic caspases activate. Around the core a penumbra forms — functionally silent but still viable tissue. The size and fate of the penumbra depend on collateral flow and time to reperfusion; saving it is the goal of acute therapy. Over the following days, activated microglia and neutrophils invade the lesion and a secondary inflammatory cascade ensues with IL-1β, TNF-α, IL-6 production. By 2–4 weeks a glial scar of reactive astrocytes and chondroitin sulphate proteoglycans (CSPGs) forms, physically and biochemically obstructing axonal sprouting and the integration of new synapses. By this stage, spontaneous neuroplasticity diminishes, though it does not disappear.

Standard stroke care is structured by phase. In the acute period the first line remains tPA thrombolysis within 4.5 hours of symptom onset, with extended endovascular thrombectomy windows of 6–24 hours in selected patients with confirmed viable penumbra on perfusion MRI. In the subacute and chronic periods secondary prevention is established and comprehensive rehabilitation is initiated — kinesiotherapy following Bobath or Brunnstrom principles, occupational therapy, speech therapy where aphasia is present, and modalities targeting neuroplasticity: CIMT (constraint-induced movement therapy), mirror therapy, FES, robot-assisted gait training, navigated rTMS, and tDCS. Each has its own niche and evidence base, but all leverage a single biological substrate — the brain's own neuroplasticity. The longer the post-stroke interval, the less this substrate spontaneously remodels.

Cell therapy does not replace rehabilitation; it amplifies its biological substrate. Following systemic infusion, UC-MSCs migrate to the lesion along chemotactic gradients (SDF-1/CXCR4) and over the following weeks function as a source of paracrine factors: stimulating angiogenesis (VEGF, FGF-2, IGF-1) with formation of new capillaries in the perilesional zone; switching microglial polarisation from M1 to M2 with reduction of local TNF-α and elevation of IL-10 and TGF-β; modifying the glial scar composition by lowering inhibitory CSPGs and easing axonal regrowth; and activating endogenous neurogenesis in the subventricular zone and dentate gyrus. Exosomes as a separate platform cross the blood-brain barrier and deliver microRNAs that regulate synaptic plasticity and neuronal survival. The combined effect is a widened biological window of neuroplasticity within which intensive motor and speech rehabilitation produces maximal gains. Without parallel rehabilitation, cell therapy is markedly attenuated — this is a foundational condition of our protocol.

The Hanshi United programme for stroke sequelae operationalises these principles in light of contemporary clinical evidence. Optimal initiation is 1–3 months after the acute event, when the patient is stable, reperfusion procedures (if indicated) are completed, and a secondary prevention plan is in place. The standard course consists of three procedures at 15–20 day intervals, typically combined: intrathecal administration for direct CNS impact plus intravenous for systemic immunomodulation. Recent data point to a more favourable safety profile for the IV route, so where intrathecal access is technically constrained we move to an IV-only course. In patients with chronic-phase stroke (>12 months), the effect is more modest but reproducible, particularly in speech, fine motor function, and cognitive domains. Background antiplatelet therapy and statins are not discontinued. Anticoagulants may require brief adjustment before an intrathecal procedure. All decisions are coordinated with the patient's treating neurologist.