Activation of cerebral peroxisome proliferator-activated receptors γ (PPARγ) reduces neuronal damage in the substantia nigra after transient focal cerebral ischaemia in the rat

摘要: M. Zuhayra, Y. Zhao, C. von Forstner, E. Henze, P. Gohlke, J. Culman and U. Lutzen (2011) Neuropathology Applied Neurobiology37, 738–752 Activation of cerebral peroxisome proliferator-activated receptors γ (PPARγ) reduces neuronal damage in the substantia nigra after transient focal ischaemia rat Aim: The function brain (neuronal) receptor(s) delayed degeneration loss neurones (SN) was studied rats occlusion middle artery (MCAO). Methods: PPARγ agonist, pioglitazone, or vehicle infused intracerebroventricularly over a 5-day period before, during 5 days MCAO (90 min). SN pars reticularis (SNr) compacta (SNc), analysis number tyrosine hydroxylase-immunoreactive (TH-IR) expression these were by immunohistochemistry immunofluorescence staining. effects activation on excitotoxic oxidative induced glutamate 6-hydroxydopamine investigated primary cortical expressing PPARγ. Results: Pioglitazone reduced total striatal infarct size, both parts ipsilateral SN, TH-IR SNc increased PPARγ-positive neurones. protected against damage, prevented neurites supported formation synaptic networks exposed to PPARγ-dependent mechanism. Conclusions: Activation confers neuroprotection ischaemic stroke preventing both, within peri-infarct zone death areas remote from site injury. other agonists may be useful therapeutic agents prevent progression ischaemia.