Fos, HSP-70, IL-10, CCK And PRL Immunoreactivity, And MR Spectroscopy Study Following Heat Stress And Heat Stress Induced Convulsions In Weanling Rats

Febrile seizures are common, affecting 5%-6% of infants and young children worldwide. Two mechanisms have been proposed for the etiological role of prolonged (longer than 10-15 minutes) febrile convulsions during early childhood in the development of adult temporal lobe epilepsy(TLE). Neuronal damage induced by febrile convulsions has been suggested as a mechanism for the development of mesial temporal sclerosis, the pathological hallmark of TLE. However, alternative mechanisms may exist for the correlation of prolonged febrile convulsions and TLE.These involve pre-existing, genetic or acquired, functional or structural neuronal changes, that may underlie both the prolonged febrile convulsions and the subsequent TLE.Toth showed that hyperthemic seizures, provoked by generating brain temperature seen physiologically in ill infants and children, were shown to result in structural alterations of select hippocampal and amygdala neurons for at least two weeks, but neuronal death was negligible. Dube' research further indicated that hyperthemic convulsions in the immature rat model of prolonged febrile seizures do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulants in vivo and electrical stimulation vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy.However, several key questions remained. First, what are the underlying neuroanatomical mechanisms for the rapid transduction of stressful alterations of neuronal milieu into enhanced excitability and resulting febrile convulsions? Second, what are the effects of heat stress and febrile convulsions on the gene expression in specific neuronal subtypes that should govern their functional properties? Most importantly, how to determine the subtle neuronal damage, short of overt death?To answer these questions, warm water induced rat febrile convulsion model was developed and immunohistochemistry method was used to analyze the expression of Fos, HSP-70, CCK and PRL immunoreactivity in rat brain following heat stress and febrile convulsions. Moreover, proton magnetic resonance spectroscopy was used to measure the ratios of N-acetylaspartate (NAA), Choline (cho) and lactate (Lac) to creatine (Cr) and compared among groups. The main purpose of the present study was to find out the influence of febrile convulsions on neuronal excitability, subtle injury and the underlying neuroanatomical mechanisms.Part 1 Fos, HSP-70, CCK and PRL immunoreactivityfollowing heat stress and febrile convulsions in weanling ratsObjectivesTo analyze the expression of Fos, HSP-70, CCK and PRL immunoreactivity in rat brain following heat stress and febrile convulsions, in order to find out the influence of FC on neuronal excitability, subtle injury and the underlying neuroanatomical mechanisms.MethodsWarm water induced rat FC model was developed and immunohistochemistry method was used in this study.ResultsThe immunoreactivity of FosThe distribution of Fos-IR positive neuronsVery few or no Fos-IR neurons were seen in the control rat. In contrast, subnucleus-specific Fos-IR positive neurons were found in the thalamic midline nucleus including paraventricular thalamic nucleus(PV), intermediodorsal nucleus(IMD), central medial nucleus(CM), rhomboid nucleus(Rh) and Reuniens nucleus(Re), no positive neurons were found in mediodorsal thalamic nucleus(MD), lateroposterior thalamic nucleus(LP), posterior thalamic nucleus(Po) and ventromedial thalamic nucleus(VPM). Significant expression was observed in paraventricular hypothalamic nucleus(PVN), no positive neurons were seen in lateral hypothalamic area(LH), ventromedial hypothalamic nucleus(VMH), arcuate nucleus(Arc) and supraoptic nucleus(SON). In cerebral cortex, Fos-IR neurons were distributed in piriform cortex(PIR), entorhinal cortex(Ent, mainly in II layer) , perirhinal cortex(PRH), parietal cortex(PAR), retrosplenial cortex(RSG , RSA) and frontal cortex(Fr). Very few positive neurons...