LESS
VULNERABLE TO SEIZURE-RELATED NEURONAL DAMAGE IN IMMATURE BRAIN
Cai Fangcheng
Children’s Hospital,
Chongqing University of Medical Science, Chongqing, China
Clinical data indicate that immature
brain is highly susceptible to seizure activity, particularly for the
patients younger than one year. However the status epilepticus in children
is generally reported to have a much lower mortality and morbidity than
adults. Similar result had been demonstrated in animal studies. Although
prolonged seizures in mature animal can often cause brain damage,
particularly at the region of hippocampus, immature brain appears to be
relatively resistant to these. Rats receiving kainic acid (KA) at the age
of 30 days (P30) and P60 had significant hippocampal lesions and deficits
in learning, memory, and behavior, however those lesion were not detected
in rats that received KA, other chemoconvulsants or kindling stimuli before
P20. Reasons for the relative resistance of immature brain to
seizure-induced neuronal death are not clear. Several mechanisms have been
mentioned on the basis of preliminary animal studies: ① Although immature brain is not lacking
in glutamate receptors, but in vivo glutamate is less toxic in immature
brain. After injection with equal amounts of glutamate into hippocampus,
minimal cell loss was noted in the P10 rats, the extent of the lesions in
P20 rats were smaller than those in P30 and P60 rats; ② Ca2+entry through NMDA
receptor was also exhibiting age dependent changes. Neither aglycemia nor
hypoxia could cause an increase in Ca2+ entry in younger P20
rats , whereas increased significantly in older rats; ③ Our unpublished data recently had well
shown that cell death caused by seizure is secondary to both apoptosis and
necrosis. The neuron loss at hippocampus was much more severe in mature
than immature brain although much more prolonged seizure in the later.
Dominant expressions of bcl-2 (an apoptosis inhibiting early gene) and
HSP70 were shown at the hippocampal neurons in immature brain but not in
mature brain, in constrast with strongest expressions of p53 (apoptosis
inducing gene) and NO in the later. Further studies should be done to
explore the compatibility of data between human and animal, and the
molecular biological basis of regulating the early genes of apoptosis
during prolong seizure in immature brain.