Protective Role of L-3-n-Butylphthalide in Cognitive Function and Dysthymic Disorders in Mouse With Chronic Epilepsy

Abstract

Epilepsy is a common neurological disease with recurrent seizures and neurobehavioral comorbidities, including cognitive impairment and psychiatric disorders. Recent studies suggest that L-3-n-butylphthalide (NBP), an extract from the seeds of Apium graveolens Linn. (Chinese celery), ameliorates cognitive dysfunction in ischemia and/or Alzheimer’s disease animal models. However, little is known about the role of NBP in epilepsy and the associated comorbidities. Here, using a pilocarpine-induced chronic epileptic mouse model, we found that NBP supplement not only alleviated seizure severity and abnormal electroencephalogram, but also rescued cognitive and emotional impairments in these epileptic mice. The possible underlying mechanisms may be associated with the protective role of NBP in reducing neuronal loss and in restoring the expression of neural synaptic proteins such as postsynaptic density protein 95 (PSD95) and glutamic acid decarboxylase 65/67 (GAD65/67). In addition, NBP treatment increased the transcription of neuroprotective factors, brain-derived neurotrophic factor and Klotho. These findings suggest that NBP treatment may be a potential strategy for ameliorating epileptogenesis and the comorbidities of cognitive and psychological impairments.

Reduced Acoustic Startle Response and Prepulse Inhibition in the Tg4-42 Model of Alzheimer’s Disease

“…Mice used for the PPI study were part of a longer study and got injected intraperitoneal with a solution of 5% Tween80 in 0,9% sodium chloride daily for 6 weeks, starting at 3 months. Tween-80 is commonly used as a vehicle to evaluate the behavioral effects of experimental drugs without apparent adverse side effects [30][31][32][33][34][35][36][37][38]. All animals were handled according to the guidelines of the 'Society for Laboratory Animals Science' (GV-SOLAS) and the guidelines of the 'Federation of European Laboratory Animal Science Association' (FELASA).…”

<p>The Efficacy of N-Butylphthalide and Dexamethasone Combined with Hyperbaric Oxygen on Delayed Encephalopathy After Acute Carbon Monoxide Poisoning</p>

“…In animal models of cerebral apoplexy, NBP was mainly used for inhibiting platelet aggregation, reducing thrombosis, improving microcirculation, reducing the volume of cerebral infarction, resisting oxidative stress, protecting mitochondrial function, reducing neuronal apoptosis, alleviating inflammatory reaction, mediating autophagy of nerve cells, promoting neurogenesis and targeting in several pathophysiological mechanisms, which are mainly reflected in its obvious neuroprotective effect. [16][17][18][19][20][21][22][23][24][25][26] After further studies on its application, it was found that the beneficial effects of NBP are beyond those of apoplexy. Especially in neurodegenerative disease fields, it was found that NBP and its ramifications have unique function and effects in AD, vascular dementia (VaD), PD, ALS and DEACMP treatment.…”

Efficacy of aspirin and clopidogrel combined with Butylphthalide on frequent transient ischemic attack of middle-aged and elderly patients with ABCD2

“…NBP,as an emerging anti-ischemic drug,inhibits platelet aggregation,reduces thrombosis,improves microcirculation,reduces cerebral infarction volume,resists oxidative stress,protects mitochondrial function,reduces neuronal apoptosis,and reduces in ammation,response and mediate autophagy of neurons,promote neurogenesis,etc in stroke animal models.It exerts multitargeting effects on a variety of pathophysiological mechanisms and shows obvious neuroprotective effects [7][8][9][10][11][12][13][14][15][16][17][18][19][20] .It has been found that its bene cial effect is far beyond the therapeutic scope of stroke [21,22] after further research and application of its application.Especially in the eld of neurodegenerative diseases,people have found that NBP and its derivatives are used in AD,VD,Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS) all have unique effects and e cacy [7,[23][24][25] .…”