Mdivi-1 alleviates brain damage and synaptic dysfunction after intracerebral hemorrhage in mice.

Abstract

As a selective inhibitor of mitochondrial fission protein dynamin-related protein-1 (Drp1), mitochondrial division inhibitor 1 (mdivi-1) can cross the blood-brain barrier (BBB) and exert neuroprotection. However, it remains unclear whether mdivi-1 can attenuate intracerebral hemorrhage (ICH)-induced secondary brain injury. This study was undertaken to characterize the roles of mdivi-1 in short-term and long-term behavioral outcomes, along with synaptic plasticity changes in mice after ICH. The results indicated mdivi-1 reversed Drp1 translocation and the morphologic changes of mitochondria, as well as ameliorated short-term neurobehavioral deficits, the BBB disruption and brain edema remarkably. In addition, mdivi-1 could rescue ICH-induced motor and memory dysfunctions. Mdivi-1 could also prevent ICH-induced reductions in synaptic proteins (synapsin I, PSD95) and phosphorylated cAMP-response element binding (p-CREB). In vitro, mdivi-1 inhibited hemin-induced hippocampal neuron death and improved neurite outgrowth. In conclusion, we found that mdivi-1 can alleviate short-term and long-term neurological deficits, synaptic dysfunction. These findings demonstrate that mdivi-1 may be beneficial in the treatment of secondary brain injury, synaptic dysfunction and neurological outcomes caused by ICH.

• Authors: Yunge Zhang, Tongyu Rui, Chengliang Luo, Qianqian Li
• Journal: Experimental brain research (Exp Brain Res) Vol. 239 Issue 5 Pg. 1581-1593 (May 2021) ISSN: 1432-1106 [Electronic] Germany
• PMID: 33754161 (Publication Type: Journal Article)

Chemical References

• Quinazolinones

Topics

• Animals
• Blood-Brain Barrier
• Brain Injuries
• Cerebral Hemorrhage (complications, drug therapy)
• Mice
• Mitochondrial Dynamics
• Quinazolinones (pharmacology)