The Change Of P38 MAPK Activation And The Effect On Morphology And Electrical Physiology In Rat Hippocampal Neuron Following Kainic Acid Administration

It is known that hippocampal sclerosis and astrocytic proliferations are the neuropathological features of human temporal lobe epilepsy. However, the mechanisms of the astrocyte's response to epilepsy are far from being clearly understood. Astrocyte, the most important cell performing supportive, nutritious and protective functions in the central nervous system, plays an important role in the activity of neuron through the microenvironment. Glial fibrillary acidic protein (GFAP), the unique intermediate filament of astrocyte, the expression of which increases with astrocyte activation. Therefore, GFAP is commonly used as an indicator of astrocyte's reaction under pathological condition. Epileptic seizure following hyperexcitability of neuron could induce a series of responses of cellular genes. As an immediate early gene, c-fos and its expression product, Fos protein, are widely used in the experiment to indicate the functional status of neuronal excitation. In the present study, the simultaneous responses of neuron and astrocyte to epileptic seizure induced by unilateral stereotaxic microinjection of KA into the lateral ventricle of rats were examined by using a double labeling method combining Fos and GFAP immunohistochemical staining. The relation between neuron and astrocyte following seizure could thus be revealed from the perspective oftissular morphology.It is known that epileptic seizure can lead to the secondary damage and even death of nerve cells. There is a correlation between the epileptic seizure and the damage of cellslt is considered that signal transduction is involved in cellular defect and even cell death. However, the epileptic seizure-induced signal transduction pathways, which lead to the induction of excitotoxic cell death in vivo, are largely unknown. It is recently proved that mitogen-activated protein kinases (MAPKs), a ubiquitous serine/threonine protein kinases which is the common and essential signaling pathway to mediate the nucleus responses and even cell death, includes extracellular signal-regulated protein kinase (ERK), p38 MAPK, c-Jun N-terminal protein kinase (INK), and ERK5. It is recognized that cell death involves the inhibition of ERK signaling pathway, and the activation of p38 MAPK or INK signaling pathway. But the temporally responsive patterns in activation of those kinases in hippocampus following epileptic seizure are still unclear. In order to clarify the functionary pathway of MAPKs following epileptic seizure, the activated responses of MAPKs to KA-induced epileptic seizure were detected by using Western-blotting in the present study.It is believed that epileptic seizure, one of the strongest stresses, can activate p38 MAPK by inducing phosphorylation of nerve cellular tyrosine residue. p38 MAPK, a subgroup of the MAPK superfamily, is responsible for stress response and cell death. Activated p38 MAPK can stimulate neutrophil to produce free radical and elastase which have neurotoxic effects on nerve cells. Recently, it was reported that SB203580, a special inhibitor of p38 MAPK, could relieve the nerve cell death following traumatic brain injury. However, it is still unclear that whether or not it could also protect nerve cells from damage following epileptic seizure. This issue could be clarified to some extent by using morphological method to examine impairment in neurons following KA treatment at two levels: hippocampal tissue in vivo and cultured hippocampal neuron in vitro.Epilepsy is in essence abnormal neuronal exaltation. Gutamic acid is the-16-most important excitatory neurotransmitter in central nervous svstem (CNS). There are three subtypes of ionotropic glutamate receptor in mammalian central nervous system: N-methyl-D-aspartic acid (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainat (KA) receptors. Of these, NMDA and AMPA have been well characterized. It is well known that activation of KA receptors shows an epileptogenic effect on the hippocampus. Therefore, the study on the process of physiological mechanism of...