Peroxisome proliferator-activated receptor-γ agonist pioglitazone ameliorates white matter lesion and cognitive impairment in hypertensive rats.
TL;DR: This work investigated whether peroxisome proliferator‐activated receptor‐γ agonist pioglitazone, with properties of vascular protection and antiinflammation, exerts beneficial effect in hypertensive WML rats.
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Abstract: Summary
Aims
Cerebrovascular white matter lesion (WML) is a major subtype of cerebral small vessel disease. Clinical drugs are not available for WML. We investigated whether peroxisome proliferator-activated receptor-γ agonist pioglitazone, with properties of vascular protection and antiinflammation, exerts beneficial effect in hypertensive WML rats.
Methods
Stroke-prone renovascular hypertensive rats (RHRSP) were treated with pioglitazone for 12 weeks. Morris water maze experiment was conducted to assess cognition. WML was observed by Luxol fast blue staining. Smooth muscle actin-alpha, collagen I, collagen IV, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule-1 were evaluated by immunohistochemistry. Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in brain and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were detected.
Results
Pioglitazone significantly attenuated WML in corpus callosum, caudate putamen, external capsule, and internal capsule. Cognitive impairment in RHRSP was ameliorated by pioglitazone. Pioglitazone attenuated arteriolar remodeling and reduced sICAM-1 level in serum. Pioglitazone decreased the proliferation of microglia and astrocyte and lowered the expression of proinflammatory cytokines IL-1β and TNF-α in the white matter.
Conclusions
Long-term treatment of pioglitazone has beneficial effect on hypertension-induced WML and cognition decline, which may partly through its effect on attenuation of arteriolar remodeling, endothelial activation, and brain inflammation.
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Citations
Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair.
Wei Cai,Tuo Yang,Huan Liu,Lijuan Han,Kai Zhang,Xiaoming Hu,Xuejing Zhang,Ke-Jie Yin,Yanqin Gao,Michael V. L. Bennett,Rehana K. Leak,Jun Chen,Jun Chen,Jun Chen +13 more
TL;DR: The therapeutic potential of PPARγ in stroke and brain trauma is reviewed and the novel role of PParγ in long-term tissue repair is highlighted, which lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions.
198
Multiple Factors Involved in the Pathogenesis of White Matter Lesions
TL;DR: This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors.
Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach.
TL;DR: Type 2 diabetes represents a promising focus for a precision health approach to reduce the impact of cognitive decline and dementia in older adults.
123
•Journal Article
Abstract 2595: Small Artery Structure is an Independent Predictor of Cardiovascular Events in Essential Hypertension
Ole N. Mathiassen,Niels Buus,Inger Sihm,Niels K. Thybo,Birgitte Moern,Anne Pauline Schroeder,Kristian Thygesen,Christian Aalkjaer,Ole Lederballe,Michael J. Mulvany,Kent L. Christensen +10 more
TL;DR: Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk.
118
Rodent Models of Vascular Cognitive Impairment
TL;DR: The most commonly used models, and the drugs that have been used to reduce the damage, are described.
References
Pioglitazone Exerts Protective Effects Against Stroke in Stroke-Prone Spontaneously Hypertensive Rats, Independently of Blood Pressure
Taishi Nakamura,Eiichiro Yamamoto,Keiichiro Kataoka,Takuro Yamashita,Yoshiko Tokutomi,Yi Fei Dong,Shinji Matsuba,Hisao Ogawa,Shokei Kim-Mitsuyama +8 more
TL;DR: This work provides the first evidence that pioglitazone significantly protects against hypertension-induced cerebrovascular injury and stroke by improving vascular endothelial dysfunction, inhibiting brain inflammation, and reducing oxidative stress.
Small artery structure is an independent predictor of cardiovascular events in essential hypertension.
Ole N. Mathiassen,Niels H. Buus,Inger Sihm,Niels K. Thybo,Birgitte Mørn,Anne Pauline Schroeder,Kristian Thygesen,Christian Aalkjaer,Ole Lederballe,Michael J. Mulvany,Kent L. Christensen +10 more
TL;DR: In this paper, a follow-up survey of 159 essential hypertensive patients, who had previously been submitted to a media: lumen ratio (M: L) evaluation while participating in a clinical trial, was conducted.
Glial activation in white matter following ischemia in the neonatal P7 rat brain.
Valérie Biran,Luc-Marie Joly,Anne Héron,Agnès Vernet,Céline Véga,Jean Mariani,Sylvain Renolleau,Christiane Charriaut-Marlangue +7 more
TL;DR: The overall results suggest that the persistent activation of microglia involves a chronic component of immunoinflammation, which overwhelms repair processes and contributes to cystic growth in the developing brain.
Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma.
Quy N. Diep,Mohammed El Mabrouk,Jeffrey S. Cohn,Dierk Endemann,Farhad Amiri,Agostino Virdis,Mario Fritsch Neves,Ernesto L. Schiffrin +7 more
TL;DR: Thiazolidinedione PPAR-&ggr; activators attenuated the development of hypertension, corrected structural abnormalities, normalized cell growth, and improved endothelial dysfunction induced by Ang II and prevented upregulation of angiotensin II type 1 receptors, cell cycle proteins, and proinflammatory mediators.
Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partially Due to Peroxisome Proliferator-Activated Receptor-γ Activation in Mice With Chronic Cerebral Hypoperfusion
Kazuo Washida,Masafumi Ihara,Keiko Nishio,Youshi Fujita,Takakuni Maki,Mahito Yamada,Jun Takahashi,Xiaofeng Wu,Takeshi Kihara,Hidefumi Ito,Hidekazu Tomimoto,Ryosuke Takahashi +11 more
TL;DR: Anti-inflammatory and antioxidative effects of telmisartan that were exerted in part by peroxisome proliferator-activated receptor-&ggr; activation, but not its blood pressure-lowering effect, have protective roles against cognitive impairment and white matter damage after chronic cerebral hypoperfusion.