RGD Reference Report - Activation of cerebral peroxisome proliferator - activated receptors gamma (PPARgamma) reduces neuronal damage in the substantia nigra after transient focal cerebral ischaemia in the rat. - Rat Genome Database
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Activation of cerebral peroxisome proliferator - activated receptors gamma (PPARgamma) reduces neuronal damage in the substantia nigra after transient focal cerebral ischaemia in the rat.

Authors: Zuhayra, M  Zhao, Y  Von Forstner, C  Henze, E  Gohlke, P  Culman, J  Lutzen, U 
Citation: Zuhayra M, etal., Neuropathol Appl Neurobiol. 2011 Mar 2. doi: 10.1111/j.1365-2990.2011.01169.x.
RGD ID: 5128609
Pubmed: (View Article at PubMed) PMID:21366664
DOI: Full-text: DOI:10.1111/j.1365-2990.2011.01169.x

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

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Th  (tyrosine hydroxylase)

Genes (Mus musculus)
Th  (tyrosine hydroxylase)

Genes (Homo sapiens)
TH  (tyrosine hydroxylase)


Additional Information