Brain damage induced by experimental myoclonus seizures with different origins

Abstract

Objective To explore the possibility of brain damage caused by myoclonic seizures of different origins and its pathologic characteristics. Methods Fifty-six adult SD rats were randomly divided into pontine micturition center (PMC) microinjection group (n=16), corpus striatum (CS) microinjection group (n=16), reticular thalamic nucleus (RTN) microinjection group (n=16), and normal control group (n=8);24 infant Guinea Pigs were randomized into dorsal pons microinjection group (n=16) and normal control group (n=8);Models of myoclonic seizures of different origins were established by microinjecting SR95531 into the PMC, CS and NRT of adult SD rats, and microinjecting L-5-HTP into the dorsal pons of Guinea Pigs, respectively. Blood from femoral artery was drawn 10 and 30 minutes after the peak time of myoclonic seizures from PMC, CS and NRT areas of rats and from dorsal pons of Guinea Pigs to detect the level of neuron-specific enolase (NSE). All animals were sacrificed 10 and 30 minutes after the peak time of myoclonic seizures and the contralateral brain at the microinjecting sites were isolated for following study: morphology in the frontal cortex and the CA3 region of hippocampus was observed by HE staining and Nissl staining;apoptosis cells in the frontal cortex and the CA3 region of hippocampus were detected by TUNEL;protein expressions of apoptosis-related Bcl-2 and Bax were detected by immunohistochemistry. Results Significant neurodegeneration and neuronal necrosis were found by HE staining in the frontal cortex and the CA3 region of hippocampus of the myoclonus originating from PMC, CS and NRT;however, no obvious histopathologic changes were observed in the cortex of Guinea Pigs with myoclonus arising from the dorsal pons. Cell count at the frontal cortex by Nissl staining was less by 56.3%-66% (30 minutes of peak time) than that in the normal control group;however, no obvious loss of cell was observed in the cortex of the Guinea pigs with myoclonus originating from dorsal pons. The serum level of NSE was increased in all rats with myoclonus originating from PMC, CS and NRT, especially in those from PMC. TUNEL-positive cells in the frontal cortex and hippocampus caused by myoclonic seizures originating from PMC, CS and NRT were increased by 20.4-40.7 times remarkably as compared with those in the controls, but no significant increase of apoptosis cells in the Guinea pigs with myoclonus originating from dorsal pons was noted. As compared with those in the controls, significant increase of Bax protein expression and obvious decrease of Bcl-2 protein expression in the frontal cortex and hippocampus of those animals with myoclonus arising from PMC, CS and NRT were found (P 0.05).Conclusion The myoclonus seizure arising from the axis of cortical-thalamus but not the dorsal pons can induce the decrease of neurocytes in the susceptive area of cortex and CA3 region. The brain damage in the cortex with the myoclonic seizures originating from the axis of cortical-thalamus is caused by the epileptic discharges of myoclonus which activates the process of necrosis and apoptosis of the neurocytes in brain, which belongs to the brain injury induced by seizures. However, there is no obvious damage in cortex of the models with the myoclonus originating from the dorsal pons of Guinea Pigs. Key words: Myoclonus; Axis of cortical-thalamus; Apoptosis; Necrocytosis