theanine and Infarction--Middle-Cerebral-Artery

While the neuroprotective effect of green tea (Camellia sinensis) might be explained by the presence of amino acid L-theanine in the tea leaves, it is not known whether postischemic administration of L-theanine could also provide neuroprotection. In the present study, we investigated the neuroprotective effect of L-theanine (1 and 4 mg/kg) administered at 3, 12, and 24 h after reperfusion in the rat model of stroke. We also studied the effect of L-theanine on brain injury caused by exogenous administration of N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate/kainate receptor agonists during reperfusion. Rats were subjected to 30-min middle cerebral artery occlusion followed by 48-h reperfusion. Neurological deficit and infarct size were determined at the end of reperfusion. At 3 and 12 h, but not at 24 h of reperfusion, L-theanine substantially reduced the size of brain infarct. Neurological status was improved when L-theanine was administered 3, 12, and 24 h after reperfusion. Repeated intrastriatal injections of L-theanine at a total dose of 800 µg/kg during reperfusion prevented brain injury caused by glutamate receptor agonists. In conclusion, L-theanine at reperfusion exerts neuroprotective effect in the in vivo rat model of stroke. Local treatment with L-theanine at reperfusion prevents glutamate receptor agonist-mediated brain injury.

Topics: Animals; Brain; Camellia sinensis; Excitatory Amino Acid Agonists; Glutamates; Infarction, Middle Cerebral Artery; Male; N-Methylaspartate; Neuroprotective Agents; Rats; Rats, Wistar; Receptors, Glutamate; Reperfusion Injury; Tea

We investigated the involvement of gamma-aminobutyric acid(A) (GABA(A)) receptors in the neuroprotective effect of gamma-glutamylethylamide (theanine), a component of Japanese green tea, following a 4-h middle cerebral artery (MCA) occlusion in mice. Theanine (1 mg/kg) reduced the size of the cerebral infarct and alterations of NeuN, GFAP, and Iba 1 expression levels at 24 h after MCA occlusion. This neuroprotective effect of theanine was prevented by bicuculline (GABA(A)-receptor antagonist, 10 mg/kg) but not 3-mercaptopropionic acid (glutamate decarboxylase inhibitor). These results suggest that the neuroprotective effect of theanine is mediated, at least in part, by GABA(A) receptors.

Topics: Animals; Brain Ischemia; Calcium-Binding Proteins; Camellia sinensis; Disease Models, Animal; DNA-Binding Proteins; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Glutamates; Infarction, Middle Cerebral Artery; Male; Mice; Microfilament Proteins; Nerve Tissue Proteins; Neuroprotective Agents; Nuclear Proteins; Receptors, GABA-A; Tea

In the present study, we examined the neuroprotective effect of gamma-glutamylethylamide (theanine) on the ischemic brain damage in a middle cerebral artery occlusion model in mice. Theanine was injected i.p. 3 h after the occlusion or immediately before and 3 h after the occlusion. Theanine (1 mg/kg) significantly decreased the size of the cerebral infarcts 1 day after the occlusion. In contrast, theanine did not affect the cerebral blood flow, brain temperature and physiological variables (pH, pCO(2), pO(2) and hematocrit) in this model. These results suggest that theanine directly provides neuroprotection against focal cerebral ischemia and may be clinically useful for preventing cerebral infarction.

Topics: Analysis of Variance; Animals; Cerebral Infarction; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamates; Infarction, Middle Cerebral Artery; Male; Mice; Neuroprotective Agents; Tetrazolium Salts