4- hydroxy-3,5-di-tret-butyl cinnamic acid restores the activity of the
hippocampal mitochondria in rats under permanent focal cerebral ischemia
Abstract
Background and Purpose: Ischemic stroke remains one of the leading
causes of death in the population. In addition, mitochondrial
dysfunction is an essential part of the pathogenesis of cerebral
ischemia and is a promising pharmacotherapeutic target. Experimental
Approach: the work was performed on male Wistar rats, which were
simulated cerebral ischemia by irreversible occlusion of the middle
cerebral artery. 4-hydroxy-3,5-di-tret-butyl cinnamic acid (25 mg/kg, 50
mg/kg and 100 mg/kg) was injected intraperitoneally for 3 days after
ischemia (daily). On the 4th day of the experiment, the changes of rat’s
cognitive functions in the Morris water maze test, cellular respiration
processes, the activity of the mitochondrial respiratory chain complexes
and citrate synthase activity, the intensity of oxidative stress and
apoptosis reactions were assessed. Key Results: it was found that the
administration of 4-hydroxy-3,5-di-tret-butyl cinnamic acid at doses of
25 mg/kg and 50 mg/kg practically equivalently promotes the restoration
of aerobic metabolism reactions and the activity of the mitochondrial
respiratory chain complexes, decrease of the intensity of oxidative
stress reactions and apoptosis, as well as an increase in the activity
of citrate synthase. As a result, the restoration of mitochondrial
function in the hippocampal cells contributed to the restoration of the
animal’s spatial memory. Conclusion and Implications: a study showed
that 4-hydroxy-3,5-di-tret-butyl cinnamic acid at doses of 25 mg/kg and
50 mg/kg has a neuroprotective effect on hippocampal neurons under
conditions of permanent occlusion of the middle cerebral artery,
realized by restoration of mitochondrial function.