Table 4.
Exercise and NIBS as the main rehabilitative interventions can promote post-stroke recovery by targeting microglia. ↑, upregulate; ↓, downregulate; MCAO, middle cerebral artery occlusion; dMCAO, distal MCAO; PT, photothrombosis; rTMS, repetitive transcranial magnetic stimulation; tDCS, transcranial direct current stimulation; TUS, transcranial ultrasound stimulation; tFUS, transcranial focused ultrasound stimulation; TBS, theta-burst stimulation; HIT, high-intensity; MOD, moderate-intensity; IL-4, interleukin-4; NLRP3, NOD-like receptor thermal protein domain associated protein 3; IL-10, interleukin-10; p75NTR, P75 neurotrophin receptor; BDNF, brain-derived neurotrophic factor; IFN-γ, interferon-γ; Gal-3, galectin-3; Syn, synaptophysin; PSD-95, postsynaptic density protein 95; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor; HIF-1α, hypoxia-inducible factor-1α; TLR4, toll-like receptor 4; NF-κB, nuclear factor kappa-B; STAT6, signal transducer and activator of transcription 6; GABA, γ-aminobutyric acid; IL-10R, interleukin-10 receptor.
| Type | Treatment (Intensity, Time, Frequency, Duration) | Model | Effect on Microglia | Outcome | Reference | |
|---|---|---|---|---|---|---|
| Exercise | Treadmill exercise | 12 m/min; 30 min/day; 3 or 6 consecutive days |
Rats (MCAO) | IL-4↑ M1-like markers↓ M2-like markers↑ |
Improving neurobehavioral outcomes | [270] |
| 5–6 m/min; 5 min/day; 3 consecutive days |
Mouse (MCAO) | NLRP3↓ | Showing better improvements at functional levels | [268] | ||
| HIT program: 10 days (>25 m/min) MOD program: 2 days (<20 m/min) |
Rats (MCAO) | IL-10↑, p75NTR↑, BDNF↑ | Promoting cerebral plasticity | [269] | ||
| 30 min/day; 5 days/week; 4 weeks |
Mouse (MCAO) | Iba1+↑ (hippocampal CA1 region) | Alleviating increased neuroinflammation | [271] | ||
| 25 cm/s; 30 min/day; 3 days/week 4.5 weeks |
Mouse (MCAO) | IL-10↑, NLRP3↑, IFN-γ↑, Gal-3↓ (caused by stress) | Having beneficial neuro-inflammatory effects; inducing detrimental stress response by forced running |
[280] | ||
| 10 m/min; 60 min/day; 5 weeks |
Mouse (microinjection of collagenase into the striatum region) | CD36/Iba1-double positive cells↑ | Contributing to neuroprotection | [278] | ||
| 12 m/min; 30 min/day; 5 times/week; 4 weeks |
Rats (MCAO) (exosomes injection) | Excessive microglial activation↓, Syn↑, PSD-95↑ | Regulating synaptic plasticity and protecting neural function | [273] | ||
| Skilled reaching training of the impaired forelimb | 5 days/week; 14 or 42 days |
Rats (PT) | Excessive microglial activation↓ | Modulating perilesional cellular plasticity and contributing to a better functional recovery | [276] | |
| 10 or 42 days | Rats (PT) | Excessive microglial activation↓ | Improving functional recovery | [277] | ||
| rTMS | Continuous TBS | 5 min (3 pulses of 50 Hz repeated every 200 ms); 5 days |
Rats (PT) | Pro-inflammatory cytokines↓ | Improving the local neuronal microenvironment | [281] |
| 5 min (3 pulses of 50 Hz, repeated every 200 ms); 6 days |
Rats (PT) | TGF-β↑, VEGF↑, HIF-1α↑ | Presenting protective effects in the context of ischemic stroke; contributing to vascular repair and protection |
[282] | ||
| Intermittent TBS | Ten 50 Hz bursts with 3 pulses each repeated 20 times at 5 Hz intervals; twice per day; 7 continuous days |
Mouse (MCAO) | TLR4/NF-κB/NLRP3 signaling pathway↓ | Alleviating locomotor deficits and neuronal pyroptosis | [283] | |
| High frequency | 10 Hz rTMS with a total of 60 trains; 20 pulses per train (1200 pulses); 10 s intertrain interval; for 11 min 44 s |
Rats (MCAO) | NF-κB↓, STAT6↓ | Promoting neurogenesis and improving neural function recovery | [284] | |
| tDCS | Cathodal | 500 µA, 15 min; once per day; 10 days |
Rats (MCAO) | Iba1+↓ Pro-inflammatory factors↓ Anti-inflammatory factor↑ |
Accelerating recovery from neurologic deficit and brain damage | [285] |
| 250 µA; 40 min; 1 day |
Mouse (PT) | CD206↑ CD68↓ |
Being effective from a functional point of view | [286] | ||
| 250 µA; 40 min |
Mouse (MCAO) | Iba1+↓ GABA and glutamate↓ |
Exerting a measurable neuroprotective effect | [287] | ||
| Anodal | 250 µA; 15 min; 10 days |
Mouse (MCAO) | Iba1+↓ | Inducing regeneration and promoting functional recovery | [288] | |
| Cathodal or anodal | 250 µA (110.13 A/m2) or 500 µA (220.3 A/m2); 15 days |
Mouse (PT) | CD16/32↓, Iba1+↓ | Impacting neurogenesis and influencing functional recovery | [289] | |
| TUS/ tFUS |
Low intensity | 528 mW/cm2; 5 days; 15 min/day; 5 days before MCAO |
Mouse (MCAO) | VEGF↑, BDNF↑, Caspase-3↓ | Ameliorating brain damage | [290] |
| 86 mW/cm2; 60 min |
Rats (dMCAO) | Inflammatory factors↓ | Increasing cerebral blood flow and supporting neuroprotection | [291] | ||
| 0.5 MHz; 120 mW/cm2; 7 consecutive days; |
Mouse (MCAO) | M2 microglia↑ IL-10 and IL-10R↑ |
Promoting neurorehabilitation | [292] |