Effects of Protocatechuic Acid (PCA) on Global Cerebral Ischemia-Induced Hippocampal Neuronal Death

Abstract

Global cerebral ischemia (GCI) is one of the main causes of hippocampal neuronal death. Ischemic damage can be rescued by early blood reperfusion. However, under some circumstances reperfusion itself can trigger a cell death process that is initiated by the reintroduction of blood, followed by the production of superoxide, a blood–brain barrier (BBB) disruption and microglial activation. Protocatechuic acid (PCA) is a major metabolite of the antioxidant polyphenols, which have been discovered in green tea. PCA has been shown to have antioxidant effects on healthy cells and anti-proliferative effects on tumor cells. To test whether PCA can prevent ischemia-induced hippocampal neuronal death, rats were injected with PCA (30 mg/kg/day) per oral (p.o) for one week after global ischemia. To evaluate degenerating neurons, oxidative stress, microglial activation and BBB disruption, we performed Fluoro-Jade B (FJB), 4-hydroxynonenal (4HNE), CD11b, GFAP and IgG staining. In the present study, we found that PCA significantly decreased degenerating neuronal cell death, oxidative stress, microglial activation, astrocyte activation and BBB disruption compared with the vehicle-treated group after ischemia. In addition, an ischemia-induced reduction in glutathione (GSH) concentration in hippocampal neurons was recovered by PCA administration. Therefore, the administration of PCA may be further investigated as a promising tool for decreasing hippocampal neuronal death after global cerebral ischemia.

Transient Receptor Potential Melastatin 2 (TRPM2) Inhibition by Antioxidant, N-Acetyl-l-Cysteine, Reduces Global Cerebral Ischemia-Induced Neuronal Death

“…However, during many neurological injuries that include ischemic stroke [ 12 ] and traumatic brain injury [ 25 ] damage leads to an ionic imbalance, which in turn allows for the initiation of multiple neurodegenerative cascades. Our previous studies have focused on these mechanisms that follow ionic imbalance in several neurological diseases, such as global ischemia [ 13 , 47 ], hypoglycemia [ 48 ], and traumatic brain injury [ 49 ]. In particular, we have focused on the abnormal phenomenon of excessive release of vesicular zinc ions following brain injuries and its subsequent cellular pathology.…”

“…Predicted steps of zinc-related neuronal death are as follows. (1) GCI induces vesicular zinc release from the pre-synaptic terminal to the synaptic cleft [ 10 , 13 ], where it translocated into post-synaptic neurons via the non-selective cation channel, TRPM2 [ 50 , 61 ]. In the post-synaptic neurons, translocated zinc contributes several deleterious cascades such as apoptosis [ 62 , 63 ], necrosis [ 63 ], as well as ROS-producing signaling.…”

“…Adhesive removal test: to test whether NAC restores against GCI-induced sensorimotor deficit, all of the experimental groups were evaluated using the adhesive removal test method for 7 consecutive days after GCI. This behavior test was conducted with reference to previous descriptions [ 13 , 71 ]. To explain again in detail, the overall evaluation process was divided into the following steps.…”

“…Under the ischemic condition, disruption of brain homeostasis is disturbed and cell death mechanisms are initiated. This cerebral injury leads to an alteration in ionic balance within the intra-extracellular space [ 6 ], reactive oxygen species (ROS) production [ 7 ], microglia [ 8 ] and astrocyte [ 9 ] activation, zinc accumulation [ 10 ], and neuronal cell degeneration [ 11 , 12 , 13 ] in the brain. Blockage of blood flow to the brain by ischemic insult causes tissue infarction, dysfunction of ionic balance, and intracellular calcium overload [ 14 ].…”

Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer’s Disease

“…Malvidin-3-O-glucoside, quercetin glucuronide, 3-hydroxybenzoic and 3-hydroxyphenylpropionic acids were able to restore synaptic plasticity in a neuroticism-like induced-situation by affecting the expression of genes involved in protein translation, as demonstrated in a model of mice primary hippocampal neurons [ 156 ]. In addition, in vivo, protocatechuic acid at a dose of 30 mg/kg prevented ischemia-induced BBB disruption and inflammatory responses mediated by microglia and astrocytes [ 157 ].…”