TABLE 2.

Drugs targeting mitochondrial dynamics after ischemic stroke.

Target	Treatment	Mechanism	Effect	References
Inhibit mitochondrial fission	Atractylenolide III	Reduce Drp1 phosphorylation and translocation by inhibiting the JAK2/STAT3 pathway	Attenuate cerebral edema and neurological deficits	Zhou et al., 2019a
	AG490
	miR-7 mimics	Repress α-synuclein, a protein that induces mitochondrial fragmentation	Reduce the post-ischemic lesion volume, accelerate motor function recovery, and ameliorate motor and cognitive deficits in mice	Kim et al., 2018
	Nitric Oxide Synthase 3 (NOS3) inhibition	Regulate Miro-2 levels and prevent mitochondrial division,	Promote axonal functional recovery	Bastian et al., 2018
	peptide P110	Inhibit the interaction between Drp1 and Fis1	Increase neuronal cell viability by reducing apoptosis and autophagic cell death	Qi et al., 2013
	photobiomodulation therapy	Inhibit hypoxic-ischemic-induced mitochondrial fragmentation	Reduce neuronal apoptosis in neonatal hypoxic-ischemic encephalopathy	Tucker et al., 2018
Promote mitochondrial fusion	Melatonin	Upregulate Opa1 expression by activating the Yap-Hippo pathway	Reduce infarct size and cerebral reperfusion stress, inhibit neuronal death	Wei et al., 2019
Restore the balance of mitochondrial dynamics	B355252	Restore Mfn2, p-Drp1, and Fis1 levels	Decrease the mitochondrial membrane potential and ROS, reduce the autophagy induction	Chimeh et al., 2018
	deletion of Nurr1	Inhibit Fis1/Drp1 expression, reverse the levels of Mfn2 and Opa1	Reduce neuronal death	Zhang and Yu, 2018
	subcutaneous injection of G-CSF	Reduce levels of Beclin-1, Bax, Bak, and Drp1, upregulate Opa1	Reduce apoptosis, and protect neurons in cerebral ischemia	Modi et al., 2020
Others	Mitochondrial transplantation	Transfer of exogenous mitochondria through local or systemic intra-arterial injections	Reduce brain damage, cell death, and motor function in MCAO rats	Huang et al., 2016; Chang et al., 2019

B355252: 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl) phenoxy) thiophene-2-sulfon-amiden.

NOS, Nitric oxide synthase; G-CSF, granulocyte-colony stimulating factor.