Green tea polyphenol (–)‐epigallocatechin gallate reduces neuronal cell damage and up‐regulation of MMP‐9 activity in hippocampal CA1 and CA2 areas following transient global cerebral ischemia

Abstract

Previous studies have demonstrated that (-)-epigallocatechin gallate (EGCG), a green tea polyphenol, protects against ischemia and reperfusion-induced injury in many organ systems. Here, we test the hypothesis that part of EGCG's neuroprotective effects may involve a modulation of matrix metalloproteinases (MMPs) after cerebral ischemia. C57BL/6 mice were subjected to 20 min of transient global cerebral ischemia. EGCG (50 mg/kg) or vehicle (saline) was administered i.p. immediately after ischemia. Brains were examined 3 days after ischemia. The effects of EGCG on MMP (gelatinase) activity and neuronal damage in the hippocampus were assessed. Gelatin gel zymography showed induction of active forms of MMP-9 protein after transient global cerebral ischemia. In situ zymography showed that ischemic gelatinase activity occurred primarily in pyramidal neuronal areas after brain ischemia. Mice treated with EGCG showed significantly reduced gelatinase levels. Neuronal damage was evident in CA1 and CA2 pyramidal sectors, corresponding to TUNEL-positive signals. In EGCG-treated mice, delayed neuronal damage was significantly reduced compared with vehicle-treated mice. These results demonstrate that the green tea polyphenol EGCG suppresses MMP-9 activation and reduces the development of delayed neuronal death after transient global cerebral ischemia in mouse brain.

(−)-Epigallocatechin-3-gallate Protects Against Neuronal Cell Death and Improves Cerebral Function After Traumatic Brain Injury in Rats

“…EGCG treatment exhibits neuroprotective effects against ischemic injury by preventing free radical production after injury (Park et al 2009). In a rat PD model, EGCG inhibits free radical production in mitochondria of hippocampal and cortical neuronal/glial cells and exhibits a neuroprotective effect (Jang et al 2010).…”

(-)-Epigallocatechin-3-Gallate Modulates Spinal Cord Neuronal Degeneration by Enhancing Growth-Associated Protein 43, B-Cell Lymphoma 2, and Decreasing B-Cell Lymphoma 2-Associated X Protein Expression after Sciatic Nerve Crush Injury

“…The antioxidant effects of green tea catechins are well established in the literature, both in vivo and in vitro, and are beyond the scope of this study. 35,39,40 Our study explores the effect of EGCG on several genes and their expression. GAP-43 is a membrane protein involved in neuronal development and plasticity.…”

Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr−/−:hApoB+/+ mice and improves cerebral blood flow

“…In the context of cerebral ischemia, gelatinases MMP-2, and especially MMP-9, contribute to the pathological process by disturbing the cerebral vasculature integrity, leading to neuroinflammation, brain edema, and hemorrhages (2,37). In this context, (Ϫ)-epigallocatechin gallate has been reported to limit brain infract size and neuronal damage by inhibiting MMP-9 activity (37,38). In the present study, we demonstrate that MMP-9 activity was significantly higher in cerebral vessels from ATX mice than from WT mice and that a chronic treatment for 3 mo with CAT significantly prevented this rise in MMP-9 activity (Fig.…”