鋰鹽為臨床上常見使用於躁鬱症和憂鬱症藥物，目前已知鋰鹽對腦神經具有多種神經保護效果。在本研究中我們以短期給藥方式治療缺血性中風大鼠並評估其腦梗塞體積、電生理和神經行為中長期檢測結果，在離體神經元實驗中分析蛋白表現，以釐清鋰鹽介導的神經保護與神經再塑機制。研究中使用中大腦動脈栓塞動物模型(MCAO)模擬缺血性中風，在手術後72小時內每24小時給予鋰鹽或生理食鹽水。在動物實驗中以體感覺誘發電位(SSEP)記錄和神經行為測試來評估鋰鹽的功能性恢復的治療效果，並以病理切片染色計算腦梗塞體積和高基氏染色評估神經棘的密度。在離體培養神經元實驗中，我們將神經元曝露於缺糖缺氧環境(OGD)中，以免疫螢光染色MAP2評估樹突軸突形態和西方點墨法評估BDNF、GAP-43、PSD-95 和 SNAP-25 蛋白表現量來了解鋰鹽於神經再塑之效益。相對於控制組，鋰鹽在傷害後7 天或 28 天皆顯著減少缺血腦的梗塞體積，並顯著改善了電生理和神經行為結果。在缺血傷害後第7天可以觀察到鋰鹽明顯增加腦皮質神經棘密度，並導致對側腦半球樹突結構的發展。在離體培養神經元中，給予鋰鹽可增加神經元的樹突長度和分支數量，並於 OGD 後 24 小時或 48 小時內增強了 BDNF、GAP-43 和 PSD-95 蛋白的表達。我們的研究證實，鋰鹽可經由調控 BDNF、GAP-43 和 PSD-95 蛋白改善缺血性傷害後神經再塑並提供中長期神經保護作用。

Lithium is well known to help patients with bipolar disorder and depression, and it has numerous neuroprotective effects on stroke. In this study, we assessed whether short-term lithium treatment would reduce brain damage and improve electrophysiological and neurobehavioral outcomes following long-term cerebral ischemia recovery. We assessed the neuroplasticity-associated protein expression in cortical neurons to determine the contribution of lithium to neuroplasticity. The beneficial neuroprotective effects of lithium were assessed using somatosensory evoked potential recordings and neurobehavioral testing. Brain infarction was assessed by Nissl-stained histology, and Golgi-cox-stained dendritic spine density was assessed. To examine the impact of lithium-induced neuroplasticity, we evaluated neuronal dendritic morphology and GAP-43, BDNF, SNAP-25, and PSD-95 protein expression in cortical neurons exposed to oxygen-glucose deprivation (OGD). Compared to the controls, lithium significantly improved the electrophysiological and neurobehavioral outcomes and reduced infarction volume at 7 or 28 days post-insults. In vivo, lithium treatment increased the cortical dendritic spine density in the cortical layers and developed a dendritic structure in the contralateral hemisphere. Lithium also improved dendritic lengths and branches in cultured cortical neurons and enhanced BDNF, GAP-43, and PSD-95 protein expression 24 h or 48 h after exposure to OGD. Our study confirmed that lithium upregulates BDNF, GAP-43, and PSD-95, partly causing the improvement in neuroplasticity and providing long-term neuroprotection in the ischemic brain.

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