罗氟司特对大鼠短暂性全脑缺血后血脑屏障的修复作用

IF 2.9 3区医学 Q2 NEUROSCIENCES Neurotoxicity Research Pub Date : 2023-08-01 Epub Date: 2023-03-16 DOI:10.1007/s12640-023-00639-2

Jéssica Mendes Bonato, Bianca Andretto de Mattos, Daniela Velasquez Oliveira, Humberto Milani, Jos Prickaerts, Rúbia Maria Weffort de Oliveira

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引用次数: 0

摘要

磷酸二酯酶4抑制剂（PDE4-I）可选择性地增加环磷酸腺苷（cAMP）水平，在诱发血脑屏障（BBB）损伤（包括局部/局灶性脑缺血）的多种神经损伤后显示出神经保护作用。本研究探讨了罗氟司特是否能在大鼠短暂性全脑缺血（TGCI）后对海马的 BBB 神经产生保护作用。瞬时全脑缺血会导致缺血大鼠CA1海马亚区整个BBB破坏，表现为埃文斯蓝（EB）和IgG外渗增加、神经变性以及Claudin-5和内皮一氧化氮合酶（eNOS）水平下调。罗氟司特减轻了BBB的破坏并恢复了CA1海马区的eNOS水平。此外，罗氟司特还能提高大鼠全身缺血后CA1亚区B2细胞淋巴瘤（BcL-2）和神经胶质抗原-2（NG2）的水平。罗氟司特对TGCI诱导的BBB破坏的保护作用可能涉及保护BBB的完整性、血管化和血管生成以及髓鞘修复。

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Blood-Brain Barrier Rescue by Roflumilast After Transient Global Cerebral Ischemia in Rats.

Phosphodiesterase 4 inhibitors (PDE4-I), which selectively increase cyclic adenosine monophosphate (cAMP) levels, have shown neuroprotective effects after several neurological injuries inducing blood-brain barrier (BBB) damage including local/focal cerebral ischemia. The present investigated whether roflumilast confers BBB neuroprotection in the hippocampus after transient global cerebral ischemia (TGCI) in rats. TGCI resulted in whole BBB disruption as measured by the increase of Evans blue (EB) and IgG extravasation, neurodegeneration, and downregulation of claudin-5 and endothelial nitric oxide synthase (eNOS) levels in the CA1 hippocampal subfield of ischemic rats. Roflumilast attenuated BBB disruption and restored the levels of eNOS in the CA1 hippocampal area. Moreover, roflumilast increased the levels of B2 cell lymphoma (BcL-2) and neuron-glial antigen-2 (NG2) in the CA1 subfield after global ischemia in rats. The protective effects of roflumilast against TGCI-induced BBB breakdown might involve preservation of BBB integrity, vascularization and angiogenesis, and myelin repair.

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来源期刊

Neurotoxicity Research 医学-神经科学

CiteScore

7.70

自引率

5.40%

发文量

164

审稿时长

6-12 weeks

期刊介绍： Neurotoxicity Research is an international, interdisciplinary broad-based journal for reporting both basic and clinical research on classical neurotoxicity effects and mechanisms associated with neurodegeneration, necrosis, neuronal apoptosis, nerve regeneration, neurotrophin mechanisms, and topics related to these themes. Published papers have focused on: NEURODEGENERATION and INJURY Neuropathologies Neuronal apoptosis Neuronal necrosis Neural death processes (anatomical, histochemical, neurochemical) Neurodegenerative Disorders Neural Effects of Substances of Abuse NERVE REGENERATION and RESPONSES TO INJURY Neural Adaptations Neurotrophin mechanisms and actions NEURO(CYTO)TOXICITY PROCESSES and NEUROPROTECTION Excitatory amino acids Neurotoxins, endogenous and synthetic Reactive oxygen (nitrogen) species Neuroprotection by endogenous and exogenous agents Papers on related themes are welcome.