Decreased Cerebrospinal Fluid and Serum Concentrations of Pigment Epithelium-Derived Factor in Drug-Refractory Epilepsy Patients
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2019, Vol 18, Issue 4
Abstract
Objectives: Considering the known potency of PEDF as a neuron protectant, we designed this study to quantitatively examine the alternation of PEDF level in the CSF of drug-effective epilepsy patients compared with drug-refractory epilepsy patients and with healthy controls. Meanwhile, the serum concentrations of PEDF were detected. Design and Methods: A total of 52 patients (including 29 drug-effective and 23 drug-refractory epilepsy patients) and 20 healthy controls participated in the study. The cerebrospinal fluid (CSF) and serum concentrations of PEDF were detected in drug-effective and drug-refractory epilepsy and control groups by sandwich enzyme-linked immunosorbent assays (ELISA). Results: CSF and serum PEDF were increased in drug-effective epilepsy but were dramatically decreased in drug-refractory epilepsy compared with controls. Conclusion: For the first time, we suggest that the neurotrophic/neuroprotective activities of PEDF might contribute to the more favorable outcome in drug-effective epilepsy patients.Epilepsy is a chronic neurological condition that affects 1% of people worldwide and is characterized by unprovoked, recurrent seizures. And there is a link between epilepsy and brain damage. Apoptosis and glutamate neurotoxicity have been suggested to be involved in seizure-induced brain damage. It has been determined that apoptosis is involved in the death of neurons after status epilepticus [1] and after prolonged seizures in animal models [2-4]. Beside the modulation of caspases and Bcl-2 molecular pathways of apoptosis are now recognized in human temporal lobe epilepsy (TLE) [5]. On the other hand, in chronic epilepsy models in rodents, there is a consistent marked increase in glutamate release during seizures [6]. In evoked seizures during surgery [7] and spontaneous seizures in ambulatory patients, there is a marked, bilateral transient ictal increase in extracellular hippocampal glutamate levels [8,9]. It has been proved that, in epilepsy, glutamate is toxic to neurons [10] and it plays a major role in the initiation and spread of seizure activity in which the excitatory glutamatergic system plays an important role [11]. Pigment epithelium-derived factor (PEDF), a 50-kDa glycoprotein, was first purified from the conditioned medium of cultured primary human fetal retinal pigment epithelial cells in the late 1980s [12]. PEDF belongs to the noninhibitor serpin family group [13]. It is widely expressed in human tissues, including the adult brain, spinal cord, eye, heart [14-16]. As a multifunctional protein, it has neurotrophic, neuroprotective and antiangiogenic properties [17,18]. In the central nervous system, PEDF is a potential neuroprotective and neurotrophic factor as evidenced by its ability to protect against neuronal apoptosis and to protect neurons against glutamate neurotoxic effects during the immature period and during late postnatal life. It was found that PEDF have neurotrophic effects on primary cultures of rat striata mesencephalic (dopaminergic) neurons [19]. In addition to striatal mesencephalic (dopaminergic) neurons, PEDF exhibits neurotrophic and neuroprotective activities in primary cultures of mature and immature cerebellar granule neurons, protecting them from glutamate-mediated degeneration and from naturally occurring apoptosis [20,21]. It also protects mature and embryonic motor neurons from apoptotic and chronic glutamate-mediated degeneration [14,22]. Moreover, PEDF can protect developing primary hippocampal neurons against glutamate neurotoxicity [23]. It has been reported that PEDF concentration is significantly elevated in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients and this may be an autoprotective reaction [15]. We found an altered PEDF level in the CSF of patients with temporal lobe epilepsy (TLE) when compared with health controls [24]. Considering the known potency of PEDF as a neuron protectant, we designed this study to quantitatively examine whether concentrations of PEDF are decreased or increased in the CSF of drug-effective epilepsy patients compared with drug-refractory epilepsy patients and with healthy controls. Meanwhile, the serum concentrations of PEDF were detected.
Authors and Affiliations
Dan Chen, Zheng Xiao, Liang Wang, Fei Xiao, Zhi Qin Xi, Xue Feng Wang, Qiao Cheng
Keywords
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- EP ID EP622704
- DOI 10.26717/BJSTR.2019.18.003184
- Views 201
- Downloads 0
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