Peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduces secondary damage in experimental spinal cord injury

Abstract

Objective: To investigate the neuroprotective effects of rosiglitazone in a rat traumatic spinal cord injury (SCI) model. Methods: Adult Sprague-Dawley rats (n ¼ 12/group) underwent laminectomy (sham), SCI, SCI and rosiglitazone treatment (2 mg/kg twice daily for 7 days), or SCI and saline injection (vehicle). SCI was induced via dural application of an aneurysm clip. Spinal cord apoptosis and levels of tumour necrosis factor-a (TNFa), interleukin (IL)-1b, myeloperoxidase (MPO) and the apoptosisassociated proteins B-cell leukaemia/lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) were examined 24 h after SCI. Locomotor function was evaluated 3, 7, 10, 14 and 21 days after SCI. Results: At 24 h after SCI, apoptosis and TNFa, IL-1b and MPO concentrations were significantly lower in the rosiglitazone group than in the vehicle and SCI groups. SCI resulted in an increase in Bax and a decrease in Bcl-2, which was reversed by rosiglitazone treatment. Rats in the rosiglitazone group had significantly better functional recovery than those in the vehicle and SCI groups. Conclusion: Rosiglitazone signiEcantly improved functional recovery, probably via attenuation of the local inflammatory reaction and reduced apoptosis.

Neuroprotective and anti-inflammatory properties of a novel non-thiazolidinedione PPARγ agonist in vitro and in MPTP-treated mice

“…Therefore, in line with the in vitro results and along with the higher provisional BBB permeability displayed by MDG548, the present data suggest an increased in vivo potency of MDG548 against MPTP neurotoxicity as compared to rosiglitazone (Nevin et al, 2012). A number of studies have reported the neuroprotective activity of PPARc agonists belonging to the TZDs class in different neurodegenerative conditions (Park et al, 2007;Tureyen et al, 2007;Landreth et al, 2008;Carta, 2013;Li et al, 2013;Lourenco and Ledo, 2013;Ouk et al, 2013;Skerrett et al, 2014). In preclinical PD models, rosiglitazone and pioglitazone displayed neuroprotective properties in rodents and primates (Breidert et al, 2002;Dehmer et al, 2004;Schintu et al, 2009;Swanson et al, 2011;Laloux et al, 2012;Lee et al, 2012;Sadeghian et al, 2012).…”

Assessment of neuroprotective role of PPAR-gamma agonist in spinal cord injury as possible therapeutic agents

“…The results of another study indicate that enhanced expression levels of PPAR-gamma in microglia following ischemia delays neuronal damage by interfering with glial activation and increases the anti-inflammatory cytokines in response to ischemic damage (Lee et al, 2011). Likewise, the anti-apoptotic action of PPARgamma agonists has been demonstrated (Li et al, 2013). Moreover, according to our results, pioglitazone has the antioxidant property because it decreased the MDA levels (an index of oxidative damage) at injured areas.…”

Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair

“…A large body of evidence indicates that activation of PPARγ attenuates neural inflammation by reducing inflammatory mediators in ischemic stroke (Culman et al ., 2007), ICH (Zhao et al ., 2007; Aronowski and Zhao, 2011), TBI (Qi et al ., 2010), and SCI (Zhang et al ., 2010; Li et al ., 2013). PPARγ stimulation inhibits the expression of a wide array of pro-inflammatory mediators in microglia and macrophages, including TNF-α, IL-1β, IL-6, iNOS, inducible cyclooxygenase (COX) 2, and the IL-12 family (Bernardo et al ., 2000; Luna-Medina et al ., 2005; Storer et al ., 2005).…”