Myung-Ho Kim

The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice

Epigallocatechin gallate (EGCG) is a constituent of green tea, and increasing evidence suggests that EGCG has neuroprotective effects on oxidative stress-injured neuronal cells, especially motoneurons. Although the neuroprotective effects of EGCG have been demonstrated in Parkinsons and Alzheimers diseases and ischemic stroke models, there has been no report on the effect of EGCG on an in vivo model of amyotrophic lateral sclerosis (ALS). This study was undertaken to evaluate the effect of EGCG on ALS model mice with the human G93A mutated Cu/Zn-superoxide dismutase (SOD1) gene. We treated each group of 11 ALS model mice with EGCG (1.5, 2.9, and 5.8 microg/g body weight), dissolved in 0.5 ml of 0.9% sterile NaCl, and one group of 11 with 0.5 ml of 0.9% sterile NaCl (control group) intraorally every day after 60 days of age (presymptomatic treatment). The treatment of more than 2.9 microg EGCG/g body weight significantly prolonged the symptom onset and life span, preserved more survival signals, and attenuated death signals. These data suggest that EGCG could be a potential therapeutic candidate for ALS as a disease-modifying agent.

The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals

Poly(ADP‐ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3‐aminobenzamide (3‐AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3‐AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague–Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague–Dawley rats were used for sham operation. 3‐AB was administered to 85 rats 10 min before the occlusion [3‐AB group (n = 85) vs. control group without 3‐AB (n = 85)]. Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)‐mediated dUTP‐biotin nick end‐labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP‐ribose) polymer (PAR), cleaved caspase‐3, CD11b, intercellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), phospho‐Akt (pAkt) and phospho‐glycogen synthase kinase‐3 (pGSK‐3) were compared in the peri‐infarcted region of the 3‐AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3‐AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL‐positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase‐3, CD11b, ICAM‐1 and COX‐2 were significantly reduced, while the IRs of pAkt and pGSK‐3 were increased. These results suggest that 3‐AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.

The Role of Matrix Metalloproteinase 9 in Early Neurological Worsening of Acute Lacunar Infarction

The involvement of matrix metalloproteinases (MMPs) in ischemic-stroke-induced inflammatory response has recently been suggested; however, the relationship between MMPs and stroke progression has not been evaluated. We investigated the role of MMPs in neurological worsening of acute lacunar infarction. Forty-nine consecutive patients with an acute lacunar infarction (as defined by clinical and MRI criteria within 48 h after stroke onset) were evaluated. Clinical, biochemical, rheological, inflammatory and other parameters were compared between progressive and nonprogressive groups. Among the variables, only inflammatory parameters, including MMP-9 and erythrocyte sedimentation rate, were associated with neurological worsening of acute lacunar infarction (p < 0.05). These results suggest that the inflammatory process could play an important role in early neurological worsening of acute lacunar infarction.