TABLE 1.
Characteristics of the included studies.
| Study | Model | Experimental groups | Intervention | Outcomes |
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| Neural mitochondrial respiratory function | Neural mitochondrial biogenesis | Neural mitochondrial fusion/fission and mitophagy | Neural mitochondria-mediated apoptosis | ||||
| Zhang et al., 2013—in vivo study | Male Wistar rats with MCAO model (using ischemic tissue from the chiasma opticum to 4 mm posterior) | 20 rats/group, four groups 1. MCAO rats 2. MCAO rats (vehicle) 3. MCAO rats + Mdivi-1 (dose 1) 4. MCAO rats + Mdivi-1 (dose 2) |
Mdivi-1 dose 1 (1.2 mg/kg) and dose 2 (0.24 mg/kg), pre-treatment | Dose 1: ↓Drp-1 protein and mRNA levels Dose 2: No changes | Dose 1: ↓TUNEL apoptotic activity ↓cytochrome c protein and mRNA levels Dose 2: no changes | ||
| Ma et al., 2016—in vivo study | Male Wistar rats with MCAO model (using ischemic cortex tissue) | 10 rats/group 1. Normal rats 2. MCAO rats 3. MCAO rats + Mdivi-1 |
Mdivi-1 (1 mg/kg, i.p.), post-treatment | ↑mRNA levels of PGC-1α, NRF-1, and TFAM. | ↓ mitochondrial fragmentation. ↓mitochondrial Drp-1 protein level No change cytosolic Opa-1 protein level | ↓TUNEL apoptotic activity ↓ cytosolic cytochrome c protein level. | |
| Li et al., 2015—in vivo study | Male Sprague–Dawley rats with CA/CRP models (using hippocampal CA1 region for TUNEL assay; using total ischemic hemisphere tissue for Western blot) | 50 rats, four groups 1. Vehicle (n = 8) 2. CA/CPR rats (n = 14) 3. CA/CPR rats + Mdivi-1 dose 1 (n = 14) 4. CA/CPR rats + Mdivi-1 dose 2 (n = 14) |
Mdivi-1 dose 1 (1.2 mg/kg) and dose 2 (0.24 mg/kg), post-treatment | Dose 1: ↓mitochondrial Drp-1 protein level Dose 2: No changes | Dose 1: ↓TUNEL ↓cytosolic cytochrome c, AIF, caspase-3 protein levels Dose 2: No significant changes | ||
| Cui et al., 2016—in vivo study | Male C57BL/6 mice MCAO model (using brain tissue from ischemic striatum) | 9–11 rats/group, three groups 1. Sham 2. MCAO rats 3. MCAO rats + Mdivi-1 |
Mdivi-1 (20 mg/kg) i.p; pre-treatment | ↓ the release of ATP from neural mitochondria | |||
| Chuang et al., 2016—in vivo study | Male Sprague-Dawley rats with TGI model (using ischemic hippocampal tissue) | 4–6 rats/group, three groups 1. TGI rats 2. Vehicle TGI rats 3. TGI rats + Mdivi-1 |
Mdivi-1 (2.4 mg/kg), pre-treatment | ↓p-Drp-1 (Ser616) protein level | ↓ DNA fragmentation ↓ caspase-3 protein level | ||
| Wang et al., 2018—in vivo | Male Sprague-Dawley rats with CA/CRP models (using ischemic hippocampal tissue) | 146 rats, four groups: 1. Normal rats (n = 41) 2. CA/CRP rats (n = 12) 3. CA/CRP rats + Mdivi-1 (n = 39) 4. CA/CRP rats + Hypothermic (n = 38) |
1.2 mg/kg of mdivi-1, intravenously, post-treatment | ↑ MMP, ATP ↓ ROS level (in mitochondria) | ↓ TUNEL positive cells | ||
| Huang et al., 2021—in vivo study | Male Sprague–Dawley rats with CA/CRP model (using ischemic hippocampal tissue) | 100 rats, 4 group: 1. Normal rats. 2. CA/CRP rats 3. CA/CRP rats + Mdivi-1 4. CA/CRP rats + remote ischemic post-conditioning |
1.2 mg/kg of mdivi-1, intravenously, post-treatment | ↑ MMP | ↑mitochondrial DNA level | ↑mitochondrial fusion factor: Mfn1 protein level ↓mitophagy: PINK1 and Parkin protein levels | ↓ TUNEL positive cells |
| Zhao et al., 2014—both in vivo and in vitro study | In vivo: Male MCAO mice model (using ischemic cortex tissue) In vitro: SH−SY−5Y cells with OGD model |
In vivo: (6–9/group) 1. Sham 2. Sham + Mdivi-1 3. MCAO mice 4. MCAO mice + Mdivi-1 In vitro: 1. Normal cells 2. Normal cells + Mdivi-1 3. OGD cells 4. OGD cells + Mdivi-1 |
In vivo: Mdivi−1 (20 mg/kg), pre-treatment In vitro: mdivi-1 (10 μM), pre-treatment | In vivo ↓ ATP. In vitro ↑ MMP, ATP | ↓ in vivo mitochondrial fragmentation ↓in vitro mitochondrial fragmentation | In vivo ↓ TUNEL and the protein level of cytosolic cytochrome c. In vitro ↑ cell viability Block Bax insertion and oligomerization ↓ cytosolic cytochrome c | |
| Li et al., 2016—in vitro study | Hippocampal neurons with OGD model | 1. Control 2. Vehicle 3. OGD cells 4. OGD cells + Mdivi-1 |
mdivi-1 (50 mM), post-treatment | ↑ MMP ↑ complex I-IV activities and ↑ATP level | ↓Drp-1 protein level | ↓ Bax protein level ↑ Bcl-2 protein level | |
| Wang et al., 2014—in vitro study | Hippocampal cells with OGD model | 1. Control 2. Vehicle 3. OGD cells 4. OGD cells + Mdivi-1 |
mdivi-1 (50 μM), pre-treatment | ↓ ROS, ↑ SOD | ↓Drp-1 protein level | ↓ apoptotic cells ↓Bax and cytochrome c protein level ↑ the protein level of Bcl-2 | |
| Zhou et al., 2017—in vitro study | N2a cells with OGD model | 1. Normal cells 2. OGD cells 3. OGD cells + Mdivi-1 |
Mdivi-1 (5 μM), pre-treatment | ↓ mPTP opening, ↑ MMP | ↓Drp-1 protein level | ↓Bax, cytosolic cytochrome c, caspase-3, and caspase-9 protein levels ↓ apoptotic cells. | |
| Zhang et al., 2014—in vitro | E18 rats cortical neurons with OGD model | 1. Normal cells 2. OGD cells 3. OGD cells + Mdivi-1 |
Mdivi-1 25 μM; post-treatment | Maintain neural mitochondria number | |||
MCAO, middle cerebral artery occlusion; OGD, Oxygen-glucose deprivation; TGI, transient global ischemia; CA/CRP, cardiac arrest/cardiopulmonary resuscitation; i.p., Intraperitoneal injection; MMP, mitochondrial membrane potential; mPTP, mitochondrial permeability transition pore; ROS, reactive oxygen species; SOD, superoxide dismutase; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; NRF-1,2, nuclear respiratory factor 1 and 2; TFAM, mitochondrial transcription factor A; Drp-1, Dynamin-related protein-1; Opa1, Dynamin-like 120 kDa protein; AIF, apoptosis-inducing factor.