Table 2.
Neuro-Immunomodulatory therapies in animal experiments.
| Drug | Subject | Administration | Effects | Ref |
|---|---|---|---|---|
| IL-1 | ||||
| IL-1R antagonist | Rat tMCAO | subcutaneous (s.c.) either acutely (at reperfusion) or in a delayed manner (24 h after reperfusion) | Alleviates neurological deficits, antidepression | [133] |
| IL-1R antagonist | Rat tMCAO | s.c. 3 and 6 h post reperfusion | Neurogenesis | [134] |
| IL-1RA-PEP | Rat tMCAO | intravenous (i.v.) at reperfusion (2 h) | p65/NF-κB and p38/MAPK | [72] |
| TNFα | ||||
| exDCs transduced to overexpress soluble TNFR1 | rat, proximal tMCAO (60 min, filament) | administration (i.v.) of TNFR1 overexpressing exDCs 6 h post reperfusion | The administration of TNFR1-expressing dendritic cells resulted in a reduction in both the size of the infarct and the level of inflammation. | [135] |
| TNF monoclonal antibody | mice, proximal tMCAO (60 min, filament) | After occlusion, 1 mg/kg Etanercept or cTfRMab-TNFR was injected i.v. At either 45 or 90 min. | The application of cTfRMAb-TNFR led to a decrease in both the volume of the infarct and neural impairments. | [136] |
| IL-6 | ||||
| IL-6 | mice, distal pMCAO (electrocoagulation) | Participants were administered with an intravenous injection of either 500 ng IL-6, sIL-6R, or 500 ng IL-6, followed by 500 ng IL-6R, either at 5 min after occlusion or at both 5 and 60 min after occlusion. | The behavioral outcome was improved by IL-6, but there was no effect on infarct size. However, when IL-6 was combined with solIL-6R, there was an increase in both infarct volume and PMN count. | [137] |
| IL-6 | mice, proximal tMCAO (60 min, filament) | The injection of 10 ng anti-IL6 mAb via intracerebroventricular (i.c.v.) or the administration of 0.1 μg rIL-6 via intranasal route every 24 h for a period of 2 weeks, starting 14 days after occlusion. | The injection of Anti-IL-6 mAb through the intracerebroventricular route resulted in reduced proliferation and neuronal differentiation of neural progenitor cells in the ipsilateral SVZ and also impacted functional recovery. However, the intranasal administration of rIL-6 showed the opposite effect. | [138] |
| IL-6 | rat, tMCAO (120 min, filament) | The administration of rIL-6 was done through intraperitoneal injection at a dose of either 50 or 500 ng. | The injection of rIL-6 resulted in a reduction of infarct volume. | [139] |
| IL-10 | ||||
| IL-10 | mice, distal pMCAO (electrocoagulation) | After occlusion, an injection of 100 ng of rmIL-10 was given via i.c.v. | The injection of 100 ng of rmIL-10 directly into the cerebral ventricles 5 min after occlusion resulted in a reduction of infarct volume. | [140] |
| IL-10 | mice, proximal tMCAO (60 min, filament) | The administration of IL-10-producing B cells via intravenous injection was performed either 24 h before or 4 h after occlusion. | The administration of IL-10-producing B cells via intravenous injection led to decreased infarct volumes and reduced post-stroke inflammation. | [141] |
| IL-10 | rat, distal tMCAO (90 min, filament) | Intravenous injection of mesenchymal stem cells overproducing IL-10 was performed at 0 or 3 h after reperfusion. | The administration of intravenous mesenchymal stem cells that overproduce IL-10 resulted in a decrease in infarct volumes, improvement in motor functions, and reduction in inflammation. | [142] |
| Microglia | ||||
| PLX5622 | aged mice, tMCAO | chow diet for 21 days | increased infarct volume and decreased neurons, enhanced neuroinflammation after IS | [143] |
| PLX3397 | mice, MCAO | The AIN-76 A standard diet was administered at a dose of 40 mg/kg/day for 21 consecutive days. | The absence of microglia led to an increase in the severity of stroke. | [109] |
| Myeloid cells inhibition | ||||
| Minocycline | rat, photothrombosis-induced focal stroke | Administered intraperitoneally at a dosage of 50 mg/kg, the drug was given 1 h after stroke induction, followed by subsequent doses of 50 mg/kg at 12, 24, 36, and 48 h. | The decrease in the count of CD68-positive cells and astrogliosis resulted in functional improvement. | [144] |
| MMP | ||||
| CD147 Antagonistic peptide | mice, tMCAO | An intravenous injection of 2.5 mg/kg APN in a total volume of 100 μL was initiated at 1 h after the induction of tMCAO. | The administration of APN via intravenous injection at a dose of 2.5 mg/kg led to an improvement in acute stroke outcome on the third day. | [145] |
| αCD147 | mice, tMCAO | once daily i.v. Injection for 3 days beginning 4 h after ischemia onset. | CD147 inhibition promotes long-term functional repair after stroke | [146] |
| αCD147 | mice, tMCAO | Tail vein injection of 100 μL PBS was used to administer the antibody treatment, which was initiated 4 h after ischemia onset and repeated at 24 and 48 h. | CD147 inhibition ameliorates acute IS by reducing thrombo-inflammation | [147] |
| T lymphocytes invasion | ||||
| anti-CD49d (VLA4) | mice, tMCAO | An administration of anti-CD49d antibody (300 μg) was carried out either 24 h before or 3 h after the onset of cerebral ischemia. | failed to positively influence the stroke outcome | [148] |
| anti-CD49d (Natalizumab) | mice, thromboembolic stroke | A single intravenous dose of 250 μg was administered either 1 h or 48 h after occlusion. | The intervention did not have any impact on the lesion volume or long-term neurological deficit. | [149] |
| Fingolimod | ||||
| tMCAO, mice | 1 mg/kg on reperfusion | anti-inflammation, but did not improve endpoint outcomes at 24 h after tMCAO | [150] | |
| tMCAO, mice | FTY720 (1 mg/kg, i.p.) 30 min after reperfusion, | The administration of Fingolimod resulted in improvement of neurological performance, a reduction of infarct size and edema. | [85] | |
| tMCAO, rat | The treatment protocol involved the administration of FTY720 (0.5 mg/kg, sigma) 24 h after reperfusion, with subsequent doses given every other day. | The enhancement of memory performance after MCAO was observed with FTY720, which induced LTP via post-synaptic mechanisms. | [151] | |
| Photothrombotisis-induced cortical IS in mice. | Administered intraperitoneally at a dose of 0.3 mg/kg for 1, 7, or 14 consecutive days. | FTY720 exerted neuroprotection and promoted angiogenesis by inducing microglial M2 polarization. | [152] | |
| Chronic WM ischemic injury induced by bilateral carotid artery stenosis in mice | FTY720 (0.3 mg/kg in PBS; Cayman Chemical Company) i.p. Administration for 3, 10, or 30 consecutive days | FTY720 reduced cognitive decline and prevented WM integrity disruption. | [153] | |
Abbreviations: cTfRMAb: chimeric monoclonal antibody against the mouse transferrin receptor; exDCs: ex vivo-derived dendritic cells; IL: interleukin; IL-1RA-PEP: Interleukin-1 receptor antagonist peptide; IS: ischemic stroke; mAb: monoclonal antibody; MMP: matrix metalloproteinases; NT-pro BNP: amino-terminal pro-B-type natriuretic peptide; PMN: polymorphonuclear neutrophils; SVZ: subventricular zone; t/pMCAO: transient/permanent middle cerebral artery occlusion; TNFR1: tumor necrosis factor receptor 1; VLA4: very late antigen-4.