TDZD-8 pre-treatment in transient middle cerebral artery occlusion

• Published in: Biomedicine & aging pathology 2014-10, Vol.4 (4), p.361-367
• Main Authors: Ratilal, Bernardo Oliveira, Rocha, João Pedro Fidalgo, Fernandes, Adelaide Maria Afonso, Arroja, Mariana Moreira Coutinho, Barateiro, Andreia Pereira, Brites, Dora Maria Tuna Oliveira, Pinto, Rui Manuel Amaro, Sepodes, Bruno Miguel Nogueira, Mota-Filipe, Helder Dias
• Format: Article
• Language: English
• Subjects: GSK-3β inhibitor; Intracranial aneurysm surgery; Ischemia-reperfusion; Neuroprotection; Transient focal cerebral ischemia
• ISSN: 2210-5220; 2210-5220
• DOI: 10.1016/j.biomag.2014.07.005

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 60min 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 (5mg/kg; intravenously) was administered 10min 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