A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats

Pilipović, Kristina; Župan, Željko; Dolenec, Petra; Mršić-Pelčić, Jasenka; Župan, Gordana

doi:10.1016/j.pnpbp.2015.01.003

Cited by 32 publications

(16 citation statements)

References 139 publications

(171 reference statements)

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“…Pilipović et al reported that TBI induced COX2 overexpression and Fluoro-Jade B-stained neurodegeneration. 40 Although Günther et al replicated these findings, increased COX2 expression in male rats did not correlate with Fluoro-Jade B-stained neurodegeneration. 41 Our results show that COX2-immunopositive fluorescence did not form dot-like structures on degenerated axons or around neuronal cell bodies and dendrites.…”

Section: Discussionmentioning

confidence: 96%

Genetic and Histological Alterations Reveal Key Role of Prostaglandin Synthase and Cyclooxygenase 1 and 2 in Traumatic Brain Injury–Induced Neuroinflammation in the Cerebral Cortex of Rats Exposed to Moderate Fluid Percussion Injury

2017

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After the initial insult in traumatic brain injury (TBI), secondary neurodegeneration occurs that is intimately associated with neuroinflammation. Prostaglandin (PG) synthases and cyclooxygenase (COX) 1 and 2 may contribute to inflammation in the brain. Temporal and spatial expression features of PG and COX1 and 2 following trauma may guide the development of antineuroinflammation strategies. Here, we examined PG synthase signaling and COX1 and 2 gene expression levels and COX-1- and 2-positive cell types and their temporal localization in TBI-induced brain in an effort to reveal their participation in the disease’s evolving neuroinflammation. Using brain samples from the cerebral cortex of rats subjected to TBI model of lateral moderate fluid percussion injury (FPI), we sought to characterize the temporal (subacute TBI) and spatial (lateral cortical lesion) brain alterations accompanying the disease progression. Temporal gene expression changes of PG synthase signaling were compared between sham-operated and TBI-treated rats using microarray pathway analysis. Moreover, we examined COX1 and 2 expression patterns and their intracellular distribution in sham-operated and TBI-treated rats by immunohistochemistry. After FPI, COX1 and 2 gene expression levels, and PGE2 synthase increased while PGD2 synthase decreased, suggesting that PGE2 and PGD2 afforded contraindicative effects of inflammation and anti-inflammation, respectively. Immunohistochemical analyses showed that both COX1 and COX2 increased in a time-dependent manner in the brain, specifically in degenerating neurons of the cortex. Interestingly, the expression of COX cell type was cell-specific, in that COX1 was particularly increased in degenerating neurons while COX2 was expressed in macrophages. In view of the dynamic temporal and spatial expression of PG, COX1 and 2 gene expression and localization in the injured brain regulating PG synthase and COX1 and 2 activity will require a careful disease-specific tailoring of treatments to abrogate the neuroinflammation-plagued secondary cell death due to TBI.

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Section: Discussionmentioning

confidence: 96%

Genetic and Histological Alterations Reveal Key Role of Prostaglandin Synthase and Cyclooxygenase 1 and 2 in Traumatic Brain Injury–Induced Neuroinflammation in the Cerebral Cortex of Rats Exposed to Moderate Fluid Percussion Injury

2017

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“…Moreover, telmisartan activates PPAR-γ less robustly and differently than thiazolidinediones (rosiglitazone, pioglitazone-oral anti-hyperglycemic agents), and it does not produce the side effects that are characteristic of full PPAR-γ agonists [177]. Although the molecular effects of PPAR-γ activation are still the focus of intense research, there is an astonishing and still growing body of evidence indicating their role in pathophysiology of several neuroimmunological and neurodegenerative disorders [178] via proinflammatory gene expression inhibition, anti-oxidative actions, reduction of macrophage and microglia accumulation, reduction in rates of apoptosis, amplification of neurite extension and expression of neurofilament proteins, and, finally, improvement of brain clearance of toxic molecules (i. e., amyloid-β peptide) [179][180][181]. This broad mode of actions implicated PPARs as a therapeutic tar-get for degenerative disorders such as AD [182,183], Parkinson's disease [184], and Huntington's disease [185].…”

Section: Disorders Of Behaviormentioning

confidence: 99%

Validation of Brain Angiotensin System Blockade as a Novel Drug Target in Pharmacological Treatment of Neuropsychiatric Disorders

Wincewicz

Braszko

2017

Pharmacopsychiatry

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Retreat in psychiatric drug development results in innovative medication decline that might be at least partially overcome by adjunct therapy. New evidence from clinical studies has shown a possible role for brain Renin-Angiotensin System (RAS) in both affective and psychotic disorders. Simultaneously, rapidly accumulating data from basic studies indicate effectiveness of central RAS blockade in much broader range of neuropsychiatric disease. Recent findings implicate brain RAS, especially Angiotensin II (Ang II), in neural pathophysiology of mental disorders through neuroendocrine modulation and effects on neurotransmitter release, mostly noradrenaline, acetylcholine and dopamine. The potential effects of angiotensin-converting-enzyme (ACE) inhibition and angiotensin type 1 receptor (AT1R) blockade on treatment of mental disorders are a matter of considerable interest. This review describes involvement of brain RAS in pathophysiology of neuropsychiatric disorders and an intriguing possibilities of improvement in pharmacological treatment outcome, where using angiotensin-converting-enzyme inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB), goes beyond blood pressure control.

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“…Time is an essential component in reaching this imbalanced state and varies depending on the tissue; for example, cardiac cells can tolerate 20 min of ischemia before necrosis and hepatocytes and renal cells more than 30 min, while neuronal cells can tolerate no more than 20 min. Some tissues (e.g., skeletal muscle cells) excel compared with others and can tolerate 2 h of ischemia [2, 3, 13, 15, 53, 54, 64, 65, 91–106]. …”

Section: Imbalance In Metabolic Substrates and Oxygenmentioning

confidence: 99%

“…Normally, PPAR- γ works as a heterodimer with retinal receptor but interacts with multiple response systems in the DNA; activation of this receptor can increase the expression of MnSOD and other enzymatic scavengers and blocks the induction of apoptosis. The PPAR- γ agonists pioglitazone and telmisartan increase the bioavailability and action of PPAR- γ to improve cell survival [45–47, 53–55, 76–78, 192–194]. …”

Section: Peroxisome Proliferator Activated Receptor-γ (Ppar-γ) Agmentioning

confidence: 99%

“…In addition, atorvastatin was shown to activate nuclear receptors such PPAR- γ . Telmisartan has a similar effect and reduces OS by activating PPAR- γ , blocking the angiotensin II receptor, type 1 (AT1 receptor), increasing levels of enzymatic scavengers, and activating cell survival pathways [45–47, 53–58, 65–68, 76–78, 192–194]. …”

Section: Pleiotropic Effectsmentioning

confidence: 99%

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Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

Rodríguez-Lara

Cardona-Muñoz

Ramírez-Lizardo

et al. 2016

Oxidative Medicine and Cellular Longevity

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Ischemia/reperfusion (I/R) lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states.

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A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats

Cited by 32 publications

References 139 publications

Genetic and Histological Alterations Reveal Key Role of Prostaglandin Synthase and Cyclooxygenase 1 and 2 in Traumatic Brain Injury–Induced Neuroinflammation in the Cerebral Cortex of Rats Exposed to Moderate Fluid Percussion Injury

Genetic and Histological Alterations Reveal Key Role of Prostaglandin Synthase and Cyclooxygenase 1 and 2 in Traumatic Brain Injury–Induced Neuroinflammation in the Cerebral Cortex of Rats Exposed to Moderate Fluid Percussion Injury

Validation of Brain Angiotensin System Blockade as a Novel Drug Target in Pharmacological Treatment of Neuropsychiatric Disorders

Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

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