Verapamil Inhibits Mitochondria-Induced Reactive Oxygen Species and Dependent Apoptosis Pathways in Cerebral Transient Global Ischemia/Reperfusion

Abstract

The prefrontal cortex is the largest lobe of the brain and is consequently involved in stroke. There is no comprehensive practical pharmacological strategy for ameliorating prefrontal cortex injury induced by cerebral ischemia. Therefore, we studied the neuroprotective properties of verapamil (Ver) on mitochondrial dysfunction and morphological features of apoptosis in transient global ischemia/reperfusion (I/R). Ninety-six Wistar rats were allocated into four groups: control, I/R, I/R+Ver (10 mg/kg twice 1 hour prior to ischemia and 1 hour after reperfusion phase), and I/R+NaCl (vehicle). Animals were sacrificed, and mitochondrial dysfunction parameters (i.e., mitochondrial swelling, mitochondrial membrane potential, ATP concentration, ROS production, and cytochrome c release), antioxidant defense (i.e., superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, and caspase-3 activation), and morphological features of apoptosis were determined. The results showed that mitochondrial damage, impairment of antioxidant defense system, and apoptosis were significantly more prevalent in the I/R group in comparison with the other groups. Ver decreased mitochondrial damage by reducing oxidative stress, augmented the activity of antioxidant enzymes in the brain, and decreased apoptosis in the I/R neurons. The current study confirmed the role of oxidative stress and mitochondrial dysfunction in I/R progression and indicated the possible antioxidative mechanism of the neuroprotective activities of Ver.

Irisin Rescues Blood‐Brain Barrier Permeability following Traumatic Brain Injury and Contributes to the Neuroprotection of Exercise in Traumatic Brain Injury

“…UCP2 pumps out neuron protons under physiological conditions and lowers the concentration and gradient of protons when back in the mitochondrial matrix, reducing the number of protons flowing through ATP synthase to weaken the synthesis of ATP [ 30 ]. Meanwhile, ATP is generated when mitochondrial membrane potential (MMP) sustains oxidative phosphorylation by a potential difference caused by the numerical difference in protons on both sides of the inner membrane [ 31 , 32 ]. As a result, the activation of UCP2 can reduce MMP.…”

Hydromorphone Protects against CO2 Pneumoperitoneum‐Induced Lung Injury via Heme Oxygenase‐1‐Regulated Mitochondrial Dynamics

“…The reaction conditions were set at 25°C. A decrease in absorbance indicated mitochondrial swelling [ 26 , 27 ].…”

Global Cerebral Ischemia in Male Long Evans Rats Impairs Dopaminergic/ΔFosB Signalling in the Mesocorticolimbic Pathway Without Altering Delay Discounting Rates

“…Our results support damage to vulnerable brain areas such as the hippocampus ( Traystman, 2003 ; Auer, 2016 ) following 10-min GCI to have a negligible impact on choice impulsivity, possibly salvaging orbitofrontal cortex circuitries. In Wistar rats, reduced brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) protein and mRNA expression have been reported in the medial PFC at a longer 30-day interval following GCI ( de la Tremblaye et al, 2016 ), while significant mitochondrial damage and apoptosis in prefrontal cortical tissue were observed 96 h following 20-min global ischemia ( Jangholi et al, 2020 ). Thus, post ischemic delays and intensity of the insults appear to play a critical role in prefrontal cortical dysfunctions.…”