Figure 1

Neurodegeneration and protection in a focal cerebral ischemia model in rats. A) Histopathology of focal cerebral ischemia (tMCAO) model in rats. a) Panoramic representative image of a whole rat brain with tMCAO injury. b) Contralateral and ipsilateral images from cerebral ischemic rat tissue with Hematoxilin-eosin staining at the −3,80 mm bregma. LH = left hemisphere, RH = Right hemisphere, square = Selected area from CA1 area. Scale bar = 1,7 mm. c), d), e) Left side representative images from Sham rats and Right side representative images from ischemic rats. c) Hematoxilin-eosin staining 100x from CA1 square in b). Scale bar = 50 μm. d) Hyperphosphorylated tau immunoreactivity (AT-8) staining 40X in CA1 area. Scale bar = 70 μm. e) Fluorojade staining 10x. Scale bar = 100 μm. B), C) and D) Comparative hypothetical model of synaptic proteins alteration following cerebral ischemia and Atorvastatin treatment. B) Sham, C) Ischemia and D) ATV-treated ischemia. B) Synaptic complexes formed by proteins of synaptic adhesion (cadherins and catenins), glutamate receptors, and scaffold proteins, such as PSD-95 are associated in a normal condition (Sh = Sham). C) Glutamate receptors are uncoupled from PSD-95 and are accumulated in the cytoplasm due to retention of subunits in the endoplasmic reticulum (ER) because of the loss of transport toward synapses due to the alteration of microtubules and the cytoskeleton. Proteins that regulate the cytoskeleton, such as RhoA increased and synaptic complexes formed by the complex cadherins/catenins, glutamate receptors, and post-synaptic proteins, such as PSD-95 are lost. D) Model of protection by statins after cerebral ischemia. Synaptic complexes formed by proteins of synaptic adhesion (cadherins and catenins), glutamate receptors, and scaffold proteins, such as PSD-95 are restored in synapse, inducing neuronal connectivity. ISCH= Ischemia, ATV = Atorvastatin.