کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2576183 | 1561348 | 2014 | 7 صفحه PDF | دانلود رایگان |
There is an unmet clinical need to develop neuroprotective agents for cerebrovascular procedures requiring transient cerebral artery occlusion. This study aims to investigate the effects of a single pre-treatment dose of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a glycogen synthase kinase-3β (GSK-3β) inhibitor, in a transient focal cerebral ischemia model. Twenty-eight male adult Wistar rats were subjected to right middle cerebral artery (MCA) occlusion via intraluminal thread technique for 60 min under continuously cortical perfusion monitoring by laser-Doppler flowmetry. Rats were divided into two groups: control or treatment groups. In the treated group, TDZD-8 (5 mg/kg; intravenously) was administered 10 min before the onset of the MCA ischemia. At 24-h reperfusion, the following parameters were evaluated: neurological deficits, brain infarct volume, ipsilateral hemispheric oedema, neuron specific enolase (NSE) plasma levels, parenchyma histology (H–E staining), Fluoro-Jade positive neurons, p-Akt and total Akt expression by western blot analysis and p-Akt-positive nuclei by immunohistochemistry. Infarct volume (P < 0.001) and neurological deficits severity (P < 0.001) were reduced in TDZD-8 treated group. TDZD-8 attenuated hemispheric oedema (P < 0.001), prevented the NSE plasma level increase (P < 0.001) and diminished the number of degenerated neurons in the infarct area (P < 0.001), as shown by Fluoro-Jade staining. TDZD-8 treated rats showed few signs of perivascular oedema when compared to control group. No variations in total Akt and p-Akt expression were observed; instead immunohistochemistry showed increased p-Akt nucleus translocation in TDZD-8 treated rats (P < 0.05). TDZD-8 is a potential pre-treatment intraoperative drug to prevent neuronal injury induced by transitory artery occlusion during cerebrovascular procedures.
Journal: Biomedicine & Aging Pathology - Volume 4, Issue 4, October–December 2014, Pages 361–367