Levodopa Improves Cognitive Function and the Deficits of Structural Synaptic Plasticity in Hippocampus Induced by Global Cerebral Ischemia/Reperfusion Injury in Rats

The cognitive impairment caused by cerebral ischemia/reperfusion is an unsolved problem in the field of international neural rehabilitation. Not only ameliorates the consciousness level of certain patients who suffered from ischemia-reperfusion injury and were comatose for a long time period after cerebral resuscitation treatment, but levodopa also improves the symptoms of neurological deficits in rats with global cerebral ischemia-reperfusion injury. However, Levodopa has not been widely used as a brain protection drug after cardiopulmonary resuscitation, because of its unclear repair mechanism. Levodopa was used to study the neuroplasticity in the hippocampus of global cerebral ischemia/reperfusion injury rat model, established by Pulsinelli's four-vessel occlusion method. Levodopa was injected intraperitoneally at 50 mg/kg/d for 7 consecutive days after 1st day of surgery. The modified neurological function score, Morris water maze, magnetic resonance imaging, Nissl and TH staining, electron microscopy and western blot were used in the present study. The results showed that levodopa improved the neurological function and learning and memory of rats after global cerebral ischemia/reperfusion injury, improved the integrity of white matter, and density of gray matter in the hippocampus, increased the number of synapses, reduced the delayed neuronal death, and increased the expression of synaptic plasticity-related proteins (BDNF, TrkB, PSD95, and Drebrin) in the hippocampus. In conclusion, levodopa can improve cognitive function after global cerebral ischemia/reperfusion injury by enhancing the synaptic plasticity in the hippocampus.

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Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

Translational Neuroscience ◽

10.1515/tnsci-2021-0006 ◽

2021 ◽

Vol 12 (1) ◽

pp. 020-031

Author(s):

Kong Fu ◽

Miancong Chen ◽

Hua Zheng ◽

Chuanzi Li ◽

Fan Yang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Neurological Function ◽

Learning Ability ◽

Morris Water Maze Test ◽

Cerebral Ischemia Reperfusion ◽

Tnf Α ◽

Cerebral Ischemia Reperfusion Injury

Abstract Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

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