Although the brain accounts for only 2% of body weight, its energy demand accounts for 20% of the body’s total energy consumption (Sifat et al., 2022). Disruption of energy metabolism is a pathological feature of ischemic stroke (Yatsu et al., 1975). After ischemic stroke, brain tissue surrounding the occluded vessels becomes ischemic, and the blood flow in the core ischemic region is reduced by more than 80% (Back et al., 2004). This causes neurons to be damaged due to a sudden drop in energy supply (Lyden et al., 2019). Research has shown that among hemiplegic patients with hand dyskinesia after stroke, the ipsilateral thalamus displays severe metabolic inhibition, and thalamic metabolic activity correlates with the degree of motor function recovery, revealing the critical role of energy metabolism restoration in motor rehabilitation (Binkofski et al., 1996). Adenosine Triphosphate (ATP) exhaustion triggers ischemic cascade reactions, including failure of membrane ion pumps, cellular edema, and membrane depolarization (Lee et al., 2000; Hofmeijer and Van Putten, 2012). Neurons cannot maintain their normal transmembrane ion gradients, which triggers a series of pathophysiological processes, including excitotoxicity, mitochondrial dysfunction, oxidative and nitrative stress, neuroinflammation, protein misfolding, and apoptosis. These pathological mechanisms form a vicious cycle, ultimately leading to cell death (He Z. et al., 2020).

Chemokines, reactive oxygen species, and other factors produced by the ischemic cascade reaction trigger immune responses in the nervous system (Larrea et al., 2023). Persistent inflammation expands the extent of brain injury and severely impacts motor function after stroke (Larrea et al., 2023; Lukacova et al., 2021). Neuroinflammation directly damages local tissues in the early stages. Moreover, it promotes glial scar formation and inhibits neuronal regeneration, leading to long-term neuronal damage (Nishimura et al., 2007; Beck and Yaari, 2008). This further impairs motor function and eventually leads to chronic and persistent disability (Larrea et al., 2023; Min et al., 2012). Research confirms that excessive microglial activation after stroke significantly worsens motor function damage, which suggests that relieving neuroinflammation is crucial for recovering motor function after stroke (Lartey et al., 2014).

Disruption of energy metabolism and subsequent initiation of inflammation together lead to cellular dysfunction and apoptosis (Zhou et al., 2021; Pascotini et al., 2015). Extensive apoptosis occurs in the motor cortex, basal ganglia, and other motor control-related regions, causing disruption of the structure and function of motor circuits and ultimately leads to motor impairments. One study shows that early motor rehabilitation after ischemic stroke can protect neurons and promote the recovery of coordinated forelimb motor function by inhibiting neuronal apoptosis in middle cerebral artery occlusion (MCAO) rats (Zhang et al., 2013).

A complete neural structure is essential for the proper functioning of nerves in regulating motor activities. Given that the neural regulation of movement is a complex and precise network, injury to any component may impair motor function. After ischemic stroke, ischemic injury affects several brain regions involved in movement, leading to various motor impairments. The motor cortex exhibits distinct temporal characteristics following injury. During the acute phase, the main manifestations are muscle weakness, reduced and slowed movement. In the chronic phase, spasticity, clonus, and hypertonia occur due to the weakened inhibition of the cortex on the lower motor centers (Schieber and Poliakov, 1998; Laplane et al., 1977). The basal ganglia inhibits lower motor centers through glutamatergic and dopaminergic inputs, thereby preventing involuntary movements (Grillner et al., 2020), thus its injury primarily leads to contralateral hyperkinetic movement disorders, including dystonia, chorea, and tremor (Park, 2016). Moreover, the white matter tissue near the basal ganglia, the internal capsule, is frequently infarcted after ischemic stroke, leading to severe motor and sensory dysfunction in the contralateral limb (Horie et al., 2019). In contrast, ischemic injury in the cerebellum and brainstem is relatively rare. In over 90% of strokes, the cerebellum and brainstem structures involved in gait control remain intact (Beyaert et al., 2015). Although the spinal cord is not directly damaged after ischemic stroke, it is highly dependent on the regulation from higher centers. After ischemic stroke, the descending inhibitory signals to the spinal cord are weakened due to higher central nervous system injury, which leads to abnormal spinal excitability, increased muscle tone, and spasticity (Urbin et al., 2021; Segal, 2018).

After ischemic stroke, the nervous system initiates a spontaneous repair process to compensate for impaired motor function through limited functional recovery and compensation (Joy and Carmichael, 2021). Neuroplasticity constitutes the pivotal mechanism driving motor recovery after ischemic stroke. Through structural and functional remodeling, it reconstructs and regulates the damaged motor network to adapt to new motor requirements (Alia et al., 2017; Dimyan and Cohen, 2011). Patients often adopt new movement strategies and action patterns to replace pre-stroke movement behaviors, thereby compensating for motor function deficits (Bernhardt et al., 2017). The new motor mode often results in incomplete compensation, reduced precision, and abnormal movement patterns, which may limit motor recovery and even worsen motor impairment (Wahl et al., 2017; Whishaw, 2000). Therefore, timely and effective interventions are crucial. They promote the recovery of impaired function and prevents the spontaneous compensatory process from forming abnormal movement patterns, thereby maximizing overall motor function recovery.

Oxidative metabolism of glucose is the primary energy source for the brain, ensuring the survival and function of neurons (Zheng and Wang, 2018b). In cellular energy regulation, AMP activated protein kinase (AMPK) functions as a crucial energy sensor, detecting changes in cellular energy and regulating abnormal energy states. AMPK can be activated when energy decreases. Subsequently, it increases metabolism-related proteins expression and inhibits biosynthetic pathways to increase ATP (Hardie et al., 2012). After ischemia–reperfusion (I/R) injury, glucose metabolism in the affected hemisphere of rats is significantly lower than in the contralateral hemisphere, and EA can regulate this condition. Additionally, EA enhances energy production and reduces unnecessary energy consumption in brain tissue by activating AMPK, significantly improving gait and athletic ability in rats (Wu et al., 2017). In ischemia and hypoxia following ischemic stroke, due to inhibition of glucose oxidation metabolism, lactate can serve as an alternative energy substrate for neurons (Roumes et al., 2021; Bliss and Sapolsky, 2001). Monocarboxylate Transporter 1 (MCT1), widely distributed in rat brain tissue, promotes the unidirectional transport of monocarboxylates across the plasma membrane, including lactate and pyruvate (Vijay and Morris, 2014). EA upregulates MCT1 expression in astrocytes around the ischemic area and promotes the release of lactate produced by intracellular anaerobic fermentation into the extracellular space, which increases extracellular lactate concentration and provides energy substrates for injured neurons (Lu et al., 2015).

Mitochondria are central to cellular energy metabolism, and their dysfunction is considered a hallmark of I/R injury, making them a critical target for alleviating post-stroke motor impairments (Gibbs et al., 2016). Dysregulation of mitochondrial dynamics and quality control can lead to mitochondrial dysfunction, and even trigger mitochondrial autophagy (Wu et al., 2016). Unc-51-like kinase 1 (ULK1) plays a crucial role in the initial stages of mitochondrial autophagy (Ganley et al., 2009; Wirth et al., 2013). FUN14 domain containing 1 (FUNDC1) acts as a receptor for mitochondrial autophagy under hypoxia and is activated through phosphorylation at the Serine17 site mediated by ULK1. Upon activation, it binds to microtubule-associated protein light chain 3 (LC3) and links mitochondria and autophagosomes, promoting mitochondrial autophagy (Liu et al., 2012; Wu et al., 2014). This process is negatively regulated by the mammalian target of rapamycin (mTOR), a key modulator of cell growth. It prevents ULK1 activation by phosphorylating the Serine-757 site of ULK1, consequently inhibiting ULK1-mediated mitochondrial autophagy (Huang et al., 2011; Kim et al., 2011). EA pretreatment activates mTOR, downregulates p-ULK1, LC3-II/LC3-I, and FUNDC1 levels, which inhibits I/R-induced mitochondrial autophagy and restores mitochondrial membrane potential (MMP). This significantly reduces mitochondrial abnormalities, decreases the number of autolysosomes, which protects neurons from I/R damage and ultimately decreases longa neurological scores (Tian et al., 2022).

After ischemic stroke, severe mitochondrial damage can trigger complex neuroinflammation, which further worsens neuronal injury and significantly impedes motor function recovery. The Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway plays a particularly crucial role in acute inflammation. TLR4 is primarily responsible for recognizing damage-associated or pathogen-associated molecular patterns and initiates immune responses through binding the adaptor protein myeloid differentiation primary response 88 (MyD88) (Barton and Medzhitov, 2003; Stierschneider and Wiesner, 2023). High mobility group box 1 (HMGB1), a key nuclear protein and immune regulatory factor, is released from damaged neurons and glial cells into the extracellular space under ischemia and hypoxia (Wu et al., 2010). I/R injury promotes the rapid binding of HMGB1 to TLR4, which triggers the phosphorylation and degradation of IκB and leads to the migration of the NF-κB subunits (p65/p50) from the cytoplasm to the nucleus. Ultimately, NF-κB activates the transcription of genes related to inflammation and immunity in the nucleus, thereby triggering and aggravating inflammation (Ridder and Schwaninger, 2009; Bhatt and Ghosh, 2014). TNF receptor-associated factor 6 (TRAF6), a downstream factor of TLR4, also participates in regulating the NF-κB pathway (Song et al., 1997). It can phosphorylate IκB by activating IκB Kinase (IKK), thereby promoting the activity of the NF-κB pathway (Wang et al., 2001; Deng et al., 2000). Additionally, TRAF6 further enhances NF-κB activity by activating the c-Jun N-terminal kinase (JNK) signaling pathway, leading to sustained neuroinflammation (Darnay et al., 1999).

EA alleviates inflammation in striatal neurons of rats with cerebral ischemia by downregulating HMGB1, JNK, and p-JNK levels, thereby improving balance and motor coordination (Nie et al., 2024). Additionally, EA inhibits IκB phosphorylation and NF-κB p65 nuclear translocation by reducing TLR4 and its downstream factors, such as TRAF6, IKKβ, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). This alleviates inflammatory damage in MCAO rats and improves neurological function (Liu et al., 2016b; Han et al., 2015; Lan et al., 2013). Further research shows that EA inhibits the NF-κB pathway by downregulating the key genes expression related to NF-κB, significantly reducing IL-1β and TNF-α levels and increasing tumor necrosis factor-β (TNF-β) levels. Ultimately, EA reduces edema, neuronal damage, and inflammatory infiltration in the ischemic core area caused by I/R and reduces longa neurological scores (Zhang X. et al., 2023).

Microglia are resident immune cells in the central nervous system, playing a key role in regulating immune responses, particularly in central nervous system disorders such as stroke, Parkinson’s disease, and Alzheimer’s disease (Hu et al., 2014; Keren-Shaul et al., 2017). Following activation of the TLR4/NF-κB signaling pathway, microglia rapidly undergo activation and functional polarization. They tend to shift towards the pro-inflammatory M1 phenotype rather than the anti-inflammatory M2 phenotype. Subsequently, a series of pro-inflammatory cytokines are released, further worsening inflammation and expanding neuronal damage (Holtman et al., 2017; Shi et al., 2019). EA significantly inhibits excessive activation and proliferation of microglia in the sensory and motor cortex surrounding the infarction and prevents their polarization towards the M1 type, which reduces the expression of TNF-α, IL-1β, and IL-6 in both the cortex and serum. This alleviates I/R-induced neuroinflammation and improves motor coordination, balance, and gait in rats (Liu et al., 2016a; Ren et al., 2024). The Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is a critical intracellular signaling pathway that binds to cytokines, hormones, and other molecules through receptors on the cell surface, transmits signals to the nucleus, and regulates gene transcription (Xin et al., 2020; Renauld, 2003). In the later stages of inflammation, anti-inflammatory factors such as interleukin-4 (IL-4) and interleukin-13 (IL-13) activate JAK1, which in turn activates STAT6. Together with peroxisome proliferator-activated receptor γ (PPARγ), they promote microglia polarization towards the M2 type, ultimately fostering an anti-inflammatory response and tissue repair (He Y. et al., 2020a). EA increases the total expression of STAT6 and PPARγ in microglia and promotes their activation, thereby facilitating the polarization of M1 microglia towards M2 and regulating the levels of corresponding pro-inflammatory and anti-inflammatory factors. This reduces longa neurological scores and improves muscle strength in the hind limbs of rats (Yao et al., 2023).

Th17 cells primarily participate in immune responses by secreting pro-inflammatory factors such as interleukin-17 (IL-17), interleukin-21 (IL-21) and interleukin-22 (IL-22) (Stockinger and Veldhoen, 2007). Treg cells primarily prevent excessive immune responses and autoimmune diseases by secreting immunosuppressive factors, such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10). Under normal conditions, they inhibit overactive T helper 17 (Th17) cells and maintain immune tolerance and an anti-inflammatory response (Afzali et al., 2007; Liesz et al., 2009). The balance between Th17 cells and Treg cells is crucial in regulating neuroinflammation and restoring exercise capacity after stroke (Liu et al., 2015; Dolati et al., 2018). C-X-C motif chemokine ligand 1 (CXCL1) and C-X-C motif chemokine ligand 2 (CXCL2) are important inflammatory chemokines that promote Th17 cells differentiation and exacerbate neuroinflammation in combination with pro-inflammatory factors (Wojkowska et al., 2014). EA promotes the differentiation of Treg cells and IL-10 secretion in brain tissue, while downregulating the gene expression of CXCL1 and CXCL2, as well as the levels of interleukin-17A (IL-17A), TNF-α, and IL-1β. This ultimately reduces neuroinflammation and reduces longa neurological scores (Wang et al., 2023a, 2023b).

Caspase-mediated apoptosis plays a critical role in neuronal death after ischemic stroke (Love, 2003). Caspases are a class of cysteine proteases, including both initiator and executioner types, that play a central role in cell apoptosis. Pro-apoptotic factors regulate caspase activation along with the anti-apoptotic factor B-cell lymphoma 2 (Bcl-2), such as Bcl-2 interacting mediator of cell death (Bim), Bcl-2 antagonist of cell death (Bad), and Bcl-2 associated x protein (Bax). Mitochondria damaged by ischemic stroke release cytochrome c, which binds to the apoptotic protease activating factor 1 (Apaf-1) and procaspase-9, forming apoptotic bodies and initiating a series of apoptotic events (Zhang and Armstrong, 2007; Love, 2003). Executioner caspases, primarily caspase-3, complete the final stages of apoptosis by degrading the genome and breaking down the cytoskeleton (Unnisa et al., 2023).

The endoplasmic reticulum (ER) is the primary organelle responsible for protein synthesis, transport, and the maintenance of intracellular Calcium ion (Ca²⁺) homeostasis. The imbalance in Ca²⁺ homeostasis caused by cerebral ischemia leads to the unfolded protein response (UPR) and accumulation, which in turn induces ER stress and initiates apoptosis (Han et al., 2021; Marciniak and Ron, 2006; Walter and Ron, 2011). Studies have shown that ER stress induced by cerebral ischemia is a key pathological mechanism related to damage to neurons, glial cells, and endothelial cells (Rissanen et al., 2006; Zhao et al., 2018; Haupt et al., 2020). Targeted inhibition of ER stress and the UPR can effectively alleviate experimental I/R injury (Zhao et al., 2018; Liu et al., 2020). The UPR, activated by ER stress, activates the expression of downstream pro-apoptotic factors by core sensors including inositol-requiring enzyme 1 (IRE1), protein kinase r -like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) (Walter et al., 2018). Acupuncture reverses ischemia-induced ER swelling by downregulating the expression of p-IRE1, p-PERK, and ATF6. This inhibits the activity of pro-apoptotic factors such as JNK and C/EBP-homologous protein (CHOP), and downregulates the levels of caspase-9 and caspase-3, thereby inhibiting apoptosis of cortical penumbra neurons induced by ER stress and alleviating paralysis or spasticity after ischemic stroke (Zhang Y. et al., 2023).

The mitogen-activated protein kinase (MAPK) pathway is a crucial regulator of cell differentiation, inflammation, and apoptosis. It consists mainly of three functional branches: the extracellular signal-regulated kinase (ERK) pathway, JNK pathway, and p38 pathway. The dynamic balance between these pathways is crucial for determining cell survival or apoptosis (Xia et al., 1995; Peti and Page, 2013). Studies show that ERK1/2 is overexpressed in MCAO animals, and inhibiting ERK1/2 phosphorylation can reduce focal infarct volume and brain damage and provide neuroprotection (Zhang et al., 2010; Wang et al., 2003; Namura et al., 2001). JNK and p38 are important therapeutic targets in ischemic stroke, as they promote inflammatory responses, induce neuronal apoptosis, and exacerbate ischemic damage (Gao et al., 2005; Zheng et al., 2018a; Jiang et al., 2014; Barone et al., 2001). EA restores the balance of the ERK/JNK/p38 pathway by downregulating the activation of ERK1/2, JNK, and p38 in cortical infarcted areas. This promotes Bcl-2 expression and downregulates the levels of caspase-3 and Bim ultimately reducing longa neurological scores (Xing et al., 2018b).

Protein kinase B (Akt) is a key molecule that inhibits neuronal apoptosis (Vidal et al., 2022; Zheng et al., 2024; Liu et al., 2025). Phosphatidylinositol 3-kinase (PI3K) can induce the phosphorylation and activation of Akt. After activation, it recruits Akt and 3-phosphoinositide-dependent kinase 1 (PDK1) to the membrane by promoting the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) (Alessi et al., 1996; Stokoe et al., 1997). PDK1 phosphorylates the Threonine 308 site of Akt, enabling it to regulate the activity of various substrates such as glycogen synthase kinase 3 beta (GSK3β), Bad, and Bim, thus playing an anti-apoptotic role (Vidal et al., 2022; Kaidanovich-Beilin and Woodgett, 2011; Datta et al., 1997; Qi et al., 2006). The phosphatase and tensin homolog (PTEN) located on chromosome 10 dephosphorylates the Threonine 308 site of Akt by catalyzing the conversion of PIP3 to PIP2, thereby inhibiting the anti-apoptotic effect of Akt (Maehama and Dixon, 1998; Li et al., 1997; Lee et al., 2004). EA upregulates the phosphorylation levels of PDK1, Akt, and GSK-3β in the cortex surrounding the infarction, inhibits PTEN expression, significantly reduces caspase-3 and Bim, and reverses the decrease in Bcl-2 induced by ischemia. This significantly reduces infarct volume and decreases the proportion of apoptotic cells, so as to reduce longa neurological scores in rats with cerebral ischemia (Xing et al., 2018a).

Taken together, the major mechanisms involved in the efficacy of acupuncture in promoting motor function following ischemic stroke via improving energy metabolism, reducing neuroinflammation, and inhibiting cell apoptosis, are shown in Figure 1.

Neurotrophic factors, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), participate in the development of the nervous system and the repair process following nerve injury by binding to specific receptors. BDNF and NT4 activate cAMP response element-binding protein (CREB) by binding to tropomyosin receptor kinase B (TrkB), upregulating genes related to nerve repair and growth, and promoting neuronal repair. NGF primarily exerts its neurotrophic effect by binding to tropomyosin receptor kinase A (TrkA) (Bai et al., 2019). Vascular endothelial growth factor (VEGF) is a key growth factor responsible for the generation and expansion of blood vessels. It provides neuroprotection and promotes nerve regeneration by inducing angiogenesis (Plate et al., 1999; Böcker-Meffert et al., 2002). EA increases the expression of BDNF, NT4, and VEGF, promotes the activation of TrkB and CREB, facilitates NSCs proliferation and differentiation, thereby alleviating striatal atrophy in MCAO/R mice and restores bilateral paw motor function. Its effect is stronger than that of mouse bone mesenchymal stem cells transplantation, particularly in terms of motor function related to ipsilateral turning (Kim et al., 2018).

After activation of the corresponding signaling pathways by neurotrophic factors, cytoskeletal remodeling is initiated, and the direction of axonal growth is guided by microtubules and microfilaments, thereby promoting the reconstruction of neural networks (Markus et al., 2002; Chen et al., 2017). Neurite outgrowth inhibitor A (Nogo-A) binds to the Nogo-66 receptor 1 (NgR1) and releases Ras homolog gene family member A (RhoA) in combination with the p75 neurotrophin receptor (p75NTR) (Schwab and Strittmatter, 2014). RhoA further activates Rho kinase (ROCK), in turn leading to actin cytoskeleton recombination, resulting in cone collapse and inhibition of neurite outgrowth (Fan et al., 2016). EA combined with constraint-induced exercise upregulates the levels of NGF, VEGF, and BDNF and inhibits the expression of Nogo-A and p75NTR, which significantly improves movement balance in MCAO/R rats (Wang D. et al., 2021). Growth-associated protein 43 (GAP-43) and neurofilament 200 (NF-200) promote axonal regeneration and synaptic plasticity, while paired immunoglobulin-like receptor B (PirB) inhibits neuronal burst growth by activating RhoA, thereby suppressing motor function recovery after ischemic stroke (Deng et al., 2018). EA upregulates the expression of NF-200 and GAP-43, while inhibiting PirB and RhoA expression to relieve the inhibition of axonal regeneration, which effectively repairs the motor pathway between the brain and spinal cord, ultimately enhancing muscle strength and promoting motor function recovery in rats (Deng et al., 2016). Postsynaptic density protein 95 (PSD-95) and synapsin (SYN) are critical proteins in synapses, playing a key role in regulating synaptic strength and activity-dependent synaptic plasticity (Béïque and Andrade, 2003; Tarsa and Goda, 2002). EA improves the decreased number and ultrastructure of synapses after I/R injury by increasing the number of PSD-95-positive and SYN-positive cells, thereby promoting neural plasticity in the brain (Xie et al., 2019). Ephrin-A5 participates in synapse formation and maturation by binding to EphA receptors (Otal et al., 2006). EA upregulates ephrin-A5 expression, increases the density and length of dendritic spines in the infarcted cortical area, thereby promoting functional recovery following ischemic stroke (Ren et al., 2008).

NSCs, as the primary source of neuronal regeneration, promote neural repair and motor function recovery by proliferating, differentiating, and migrating to generate new neurons, astrocytes, and oligodendrocytes (Tang et al., 2017). Stromal cell-derived factor 1 alpha (SDF-1α) promotes neural regeneration and behavioral recovery after ischemic stroke by enhancing the recruitment of endogenous NSCs (Luo et al., 2014; Deng et al., 2021; Zhao et al., 2015). Three days of EA pretreatment increase BDNF levels in the brain tissue of photothrombosis stroke mice and upregulates SDF-1α in plasma, significantly improving vestibular motor function, sensory motor function and forelimb symmetry (Kim et al., 2013). EA also increases the number of newly formed NSCs in the hippocampus, promotes their differentiation into neurons or astrocytes, and upregulates the levels of BDNF and VEGF (Kim et al., 2014).

Neuronal excitability refers to the ability of neurons to respond to stimuli and generate action potentials, directly affecting the normal function and stability of neural circuits (Turrigiano, 2011). After ischemic stroke, the connections between different regions of the nervous system related to movement are severely disrupted, causing an imbalance in neuronal excitability and motor impairments (Li et al., 2019; Hubli et al., 2012). Glutamate (Glu), the primary excitatory neurotransmitter in the central nervous system, maintains normal neuronal excitability by mediating the influx of Ca²⁺ (Hansen et al., 2021). Under pathological conditions, abnormal accumulation of excitatory amino acids in synaptic gaps can cause sustained neuronal overexcitation, leading to synaptic transmission disorders and Ca²⁺ overload. This disrupts neural network homeostasis and damages neural circuits related to motor control. Research shows that after ischemic stroke, impaired high-level central regulatory function leads motor neurons to frequently send abnormal nerve impulses, causing sustained muscle spasms and worsening motor impairments and disabilities (Trompetto et al., 2019). Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system, produced by the decarboxylation of Glu catalyzed by glutamate decarboxylase 67 (GAD67) and degraded by GABA-transaminase (GABA-T) (Lee et al., 2019). GABA inhibits neuronal excitability through two distinct pathways. Firstly, it diminished the excitatory signals of glutamatergic neurons and inhibits Glu release via presynaptic inhibition. Secondly, through postsynaptic inhibition, it binds to GABA receptors to promote Chloride ion (Cl⁻) influx, which subsequently leads to neuronal membrane hyperpolarization and a reduction in neuronal excitability (Chalifoux and Carter, 2010; Kaila, 1994; Li et al., 2002). The Potassium-Chloride co-transporter 2 (KCC2), located on the neuronal cell membrane, maintains low intracellular Cl⁻ levels by expelling Cl⁻, thereby facilitating GABA-mediated Cl⁻ influx and effectively inhibiting excessive excitability in motor neurons (Rivera et al., 2005; Watanabe et al., 2009). Several studies show that acupuncture upregulates GABA levels, enhances the expression of KCC2 and GABAA, and inhibits GABA-T activity in the nervous system of MCAO rats, thereby restoring normal neuronal excitability and promoting functional recovery of spastic limbs after ischemic stroke (Sun et al., 2022; Mu et al., 2022; Wang J. X. et al., 2021; Wang et al., 2020).

The major mechanisms involved in the efficacy of acupuncture in improving motor function after ischemic stroke via facilitating nerve repair and regeneration and regulating neuronal excitability are shown in Figure 2.

It is a feature of acupuncture that appropriate acupoints are selected based on individual’s symptoms and syndromes (a series of clinical manifestations reflecting the pathogenesis of a disease). The choice of stimulation sites is an important factor affecting the efficacy of acupuncture. Considering that basic studies primarily focus on exploring the mechanisms of acupuncture, to optimize experimental controllability and reproducibility, a limited number of acupoints and simplified acupuncture techniques are typically used. The two most commonly used acupoints are GV20 and ST36. However, clinical studies place more emphasis on individualized treatments to achieve better effects, therefore, more acupoints are usually applied, such as GB34, LI4, GV20, LI15, LI11, SP6, and TE5. The appearance frequency of most commonly-used acupoints is shown in Table 3 and Figure 3.

Conventional treatment typically targets the affected limb to facilitate motor function restoration. Nonetheless, acupuncture applied to the healthy limb also confers significant therapeutic benefits. Research shows that activity in the healthy hemisphere is increased during the first 10 days after stroke, followed by a gradual increase in activity in the impaired hemisphere. This dynamic neural activation process is closely linked to the recovery of motor function (Marshall et al., 2000; Ward et al., 2003). When the lesion affects most of the motor-related areas, the role of the healthy hemisphere in functional reorganization and motor recovery is especially critical (Di Pino et al., 2014). One study compares the therapeutic effects of acupuncture on the healthy and affected sides. The results show that under the same acupoint selection, needling on the healthy limb has a more significant effect on improving FMA and BI scores, and reducing neurological deficit score (NDS) (Gao et al., 2012). This suggests that acupuncture on the healthy limb may promote overall motor function recovery by regulating the function of the healthy hemisphere. Its underlying mechanism requires further exploration.

Existing research and classical theories suggest that different acupuncture techniques can significantly influence treatment efficacy (Davis et al., 2012; Wang J. et al., 2021). Compared to manual acupuncture, EA provides stable and continuous stimulation and accurately activates specific acupoints by adjusting pulse width, intensity, and frequency (Zhang et al., 2022). A study showed that EA is more effective than manual acupuncture in reducing National Institutes of Health Stroke Scale (NIHSS) scores and improving FMA and BI scores (Tian et al., 2016). Additionally, transcutaneous electrical acupuncture stimulation (TEAS) stimulates acupoints directly through the skin by attaching electrode pads. Combining TEAS, particularly in 100 Hz, with routine care significantly improves FMA and BI scores, increases limb co-contraction rates, and reduces MAS score and spastic muscle activity levels in patients with post-stroke spastic hemiplegia (Wang et al., 2025). Fire needle therapy is a method of rapidly penetrating the acupoint with a red burning needle tip to treat diseases. A meta-analysis indicates that fire needle performs better in reducing MAS than manual acupuncture especially in the upper limbs. In other scales, such as FMA, BI, and NDS, fire needle also shows a more significant effect (Qiu et al., 2021). By the way, warm needle acupuncture, which combines acupuncture and moxibustion, can deeply stimulate acupoints and enhance efficacy by transmitting warmth from burning moxa wool through the needle. A network meta-analysis compares the efficacy of various acupuncture techniques and finds that warm needle acupuncture is more effective in relieving spasticity in elderly stroke survivors, while manual acupuncture was more beneficial in improving overall motor function (Zhu G. C. et al., 2024). This suggests that the personalized selection of acupuncture techniques based on specific conditions is an effective strategy for improving clinical efficacy.

The Stroke Recovery and Rehabilitation Roundtable (SRRR) classifies acute cerebral ischemia into five phases: hyperacute (within 24 h), acute (1–7 days), early subacute (7 days to 3 months), late subacute (3–6 months), and chronic (over 6 months) (Bernhardt et al., 2017). Most stroke survivors undergo spontaneous functional recovery in the early stages, but the duration varies depending on the affected neurological system (Cramer et al., 2007). For example, motor function typically improves within weeks to months after stroke, while language function recovery may take months to years (Nakayama et al., 1994). The first week to the first month after stroke is a critical period for neural plasticity, making this stage a key focus for rehabilitation therapy and clinical studies (Krakauer et al., 2012; Biernaskie et al., 2004). Although the optimal time window for acupuncture intervention remains undetermined, existing evidence indicates that earlier initiation and increased treatment frequency improve motor function and alleviate inflammatory responses (Wu et al., 2023; Xu et al., 2020). This may be linked to the mechanism of acupuncture that alleviates nerve damage during the acute phase of stroke by improving energy metabolism, regulating inflammation, and inhibiting cell apoptosis. A meta-analysis shows that early acupuncture intervention, particularly within 48 h after stroke, significantly improves FMA and BI scores, with efficacy lasting up to 15 days after onset, significantly better than late intervention (Zhuo et al., 2021). Nevertheless, current clinical studies primarily focus on the subacute and chronic phases, with relatively limited studies on the acute phase. Greater emphasis on early-stage acupuncture in future studies may help refine intervention timing and improve the efficacy of motor function recovery.

In clinical rehabilitation after ischemic stroke, a comprehensive intervention incorporating multiple treatment methods is commonly employed. Acupuncture can significantly enhance the effectiveness of motor function recovery when combined with conventional rehabilitation training, medication therapy, and other techniques. Several meta-analyses show that combining conventional rehabilitation, medication therapy, and mirror training with acupuncture further enhances motor function and accelerates the rehabilitation process (Cai et al., 2017; Lv et al., 2021; Peng et al., 2024; Tao et al., 2023; Zhan et al., 2018; Zhang et al., 2024; Zhu T. et al., 2024). Additionally, compared to using EA alone, a comprehensive plan that combines conventional rehabilitation therapy demonstrates superior performance in modulating the electromyographic frequency and amplitude in post-stroke patients with motor impairments. It also effectively enhances motor function and daily living ability (Duc Nguyen et al., 2023). These findings suggest that acupuncture, as an effective complementary therapy, is more beneficial when combined with conventional rehabilitation treatment than when used alone. In clinical practice, the cooperative effects of multiple intervention methods can optimize motor function recovery and significantly improve the quality of life. Current studies directly comparing the efficacy of acupuncture and conventional rehabilitation therapy remain limited. Future high-quality research evaluating their independent effects is needed to clarify the respective advantages of each approach and provide stronger evidence to support therapeutic strategies.