ABSTRACT
PURPOSE: To examine the cognition, spontaneous epilepsy, and electroencephalography (EEG) characteristics of rats with malformations of cortical development (MCD) and their use as an animal model for investigating the pathogenesis of intractable epilepsy and screening novel antiepileptic drugs. METHODS: An epileptic rat model of MCD was established with the F1 generation of pregnant rats after X-irradiation with 175 cGy (Group L), 195 cGy (Group M), or 215 cGy (Group H). Long-term video-EEG monitoring was used to record the seizures in the rats with MCD. Cognition was assessed with the Morris water maze. The EEGs were recorded and analyzed in the frontal and parietal lobes and hippocampi of adult rats. Finally, the brain tissues were processed for Nissl staining. RESULTS: The model groups exhibited markedly prolonged escape latencies and distinct decrements in the percent distance traveled in the target quadrant and platform-crossing frequency. These findings were dose-dependent. Frequent interictal epileptiform discharges were observed in the frontal and parietal lobes and hippocampi of adult rats, and their incidences were markedly higher in the model groups compared with that in the normal controls, with Group M having the highest incidence. Spontaneous seizures were observed in the model groups (mean incidence, 46.7%). The daily mean frequency of seizures and the incidence of spontaneous seizures were highest in Group M. Nissl staining revealed a dose-dependent pattern of hippocampal abnormalities, cortical and subcortical nodular heterotopia, and callosal agenesis in the model groups. CONCLUSION: The 195 cGy dose was most appropriate for establishing an epileptic model of MCD with X-irradiation.
Subject(s)
Cognition Disorders/etiology , Epilepsy/etiology , Malformations of Cortical Development/complications , Prenatal Exposure Delayed Effects/physiopathology , Analysis of Variance , Animals , Disease Models, Animal , Electroencephalography , Epilepsy/pathology , Female , Male , Malformations of Cortical Development/etiology , Maze Learning/physiology , Maze Learning/radiation effects , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Rats , Rats, Sprague-Dawley , Spatial Learning/physiology , Spatial Learning/radiation effects , Time Factors , X-Rays/adverse effectsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of minocycline in promoting the survival of pheochromocytoma (PCI2) cells exposed to oxygen glucose deprivation (OGD) and explore the underlying mechanisms.</p><p><b>METHODS</b>An in vitro cell model of cerebral ischemia was established by OGD for 6 h in PCI2 cells with pretreatment with minocycline or an ERK1/2 inhibitor. At 24 h after OGD injury, the cells were evaluated for cell viability by MTT assay and expressions of heme oxygenase-I (HO-I) and phospholylated extracellular signal-regulated protein kinase 1/2 (ERK1/2) by Western blotting.</p><p><b>RESULTS</b>The cell viability decreased dramatically following OGD. Pretreatment with minocycline (O.I-IO JJ.mol/L) induced a significant increase in the cell viability after OGD and caused up-regulation of HO-I protein and enhanced ERK1/2 phospholylation, and the effects were especially obvious with 1 JJ.mol/L minocycline and were abolished by inhibition of ERK1/2 activity with UOI26 (IO JJ.mol/L).</p><p><b>CONCLUSION</b>Minocycline can protect PCI2 cells against OGD-induced toxicity by up-regulating HO-I protein expression through ERKl/2 signaling pathways.</p>
