Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole-induced generalized seizures

Abstract

Erythropoietin (EPO) suppresses epileptic seizures, but the mechanism is unclear. The search for novel targets in the therapy of epilepsy has focused recently on brain inflammation since brain inflammation and the associated blood-brain barrier (BBB) damage appears to be an integral part of epilepsy pathophysiology. We examined the effects of EPO on proinflammatory mediators in brain and serum in PTZ-induced generalized seizure model. The inflammation markers (IL-1β, TNF-α, IL-6, IL-10), BBB and neuron damage markers (S100B, Neuron specific enolase; NSE, respectively) in serum and brain of Sprague-Dawley male rats were examined with the ELISA method. Nitric oxide synthase (NOS) isoforms were investigated immunohistochemically in hippocampus. EPO treatment 4 h and 24 h before PTZ administration had diverse effects. EPO treatment 4 h before PTZ administration elongated the seizure latency, decreased the inflammation and damage markers in serum and brain significantly, whereas EPO treatment 24 h before PTZ administration lowered inflammation and damage markers to control levels and decreased the seizure stage. PTZ-induced seizures increased inducible NOS (iNOS) activity and decreased endothelial NOS (eNOS) activity in hippocampus. Both EPO pretreatments reversed these effects. These findings, i.e., decreased iNOS activity and increased eNOS activity by EPO suggest the first time that the favorable effect of EPO pretreatment on inflammatory mediators triggered by PTZ-induced seizures. This can provide further insight into epilepsy treatment and new prophylactic strategies against epilepsy risk.

A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice

“…Down regulation of iNOS was found to attenuate the progress of chemically induced seizures and neuronal damage [56,57]. PTZ-induced seizures, increased iNOS activity in hippocampus [57].…”

“…PTZ-induced seizures, increased iNOS activity in hippocampus [57]. Considering the fact that higher activity of nNOS and iNOS are associated with excitotoxicity, NO formation is amplified through epileptic seizures [57].…”

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

“…Additionally, previous studies have shown that licofelone is able to decrease NO production or decrease iNOS activation in cartilage chondrocytes 54,55. It is also shown that activation of LOX and COX causes oxidative stress leading to apoptosis of GABAergic neurons56; and neuronal damage due to seizures is associated with upregulation of iNOS in hippocampus 57. It seems that variant models of seizure, source of NO, and other neurotransmitter involving during epileptogenesis are the underlying reasons for these differences.…”

Long term consequences on spatial learning-memory of low-calorie diet during adolescence in female rats; hippocampal and prefrontal cortex BDNF level, expression of NeuN and cell proliferation in dentate gyrus

“…Both the intensity and the distribution of PCNA and NeuN staining were scored. For NeuN, a histological score (HSCORE) value was derived by summing the percentages of cells that stained at each intensity multiplied by the weighted intensity of the staining (HSCORE = S Pi (i+1), where i is the intensity score and Pi is the corresponding percentage of the cells) (Bahçekapılı et al, 2014). For PCNA, the rate of PCNA (+) cells to all cells in DG was measured.…”