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Published on: November 19, 2019
[Effect of endogenous heme oxygenase-carbon monoxide on brain damage induced by recurrent febrile seizures]
Zhi-xian Yang1, Jiong Qin, Jun-bao Du
1Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Insights
The endogenous heme oxygenase (HO)/carbon monoxide (CO) system may protect against febrile seizure (FS)-induced brain damage. Inhibiting this system with ZnPPIX worsened hippocampal neuron injury in rats.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Febrile seizures (FS) are common in children, with recurrent events potentially leading to hippocampal damage and temporal lobe epilepsy.
- The endogenous heme oxygenase (HO)-carbon monoxide (CO) system's role in FS-induced brain injury is not fully understood.
Purpose of the Study:
- To investigate the effect of the endogenous HO-CO system on brain damage induced by recurrent febrile seizures in a rat model.
Main Methods:
- Recurrent febrile seizures (FS) were induced in 21-day-old Sprague-Dawley rats.
- Rats were divided into control, FS, and FS + zinc protoporphyrin (ZnPPIX) groups.
- Carbon monoxide (CO) levels, seizure characteristics, and hippocampal neuron morphology (light and electron microscopy, Nissl staining) were analyzed.
Main Results:
- Recurrent FS increased plasma CO levels, which were reduced by ZnPPIX, an HO inhibitor.
- While FS alone showed some neuronal disorganization and ultrastructural changes, ZnPPIX treatment aggravated hippocampal neuron injury and decreased neuron counts in CA1 and CA3 subfields.
- Seizure duration tended to prolong with increased seizure number in the FS group, and ZnPPIX further prolonged seizure duration and shortened latency.
Conclusions:
- The endogenous HO/CO system appears to play a protective role against febrile seizure-induced hippocampal damage.
- Inhibition of the HO/CO system exacerbates neuronal injury following recurrent febrile seizures.
Objective:
Febrile seizures (FS) are the most common seizure disorders in children. Approximately one third of children with a febrile seizure have recurrent events. Although most FS may not represent a serious health problem, those that are more prolonged and recurrent may cause hippocampal damage which is the most important pathological basis of temporal lobe epilepsy. The present study aimed to explore the effect of endogenous heme oxygenase (HO)-carbon monoxide (CO) system on brain damage induced by recurrent FS.
Method:
Twenty-four Sprague-Dawley rats aged 21 days were randomly divided into three groups: Control group (immersed in 37.0 degrees C water, n = 8), FS group (immersed in 45.2 degrees C water, n = 8), FS + zinc protoporphyrin (ZnPPIX) group (immersed in 45.2 degrees C water, n = 8). FS in rats were induced ten times in a bath of warm water, once every 2 days. The indirect production of CO in plasma was detected by a dual wavelengh spectrophotometer. The intensity, latency, duration and rectal temperature of the seizure in rats were recorded. Morphologic changes of hippocampal neurons were observed with HE staining. The ultrastructural changes of the hippocampal neurons were observed under electron microscope. Semiquantitative analysis of hippocampal neurons was carried out by using Nissl stain.
Result:
After recurrent FS, the content of CO in plasma in FS group was increased as compared with that in control group (P < 0.01). The content of CO in plasma in FS + ZnPPIX group was decreased as compared with that in FS group (P < 0.01), while no significant difference in CO content was found as compared with that in control group (P > 0.05). In FS group, with the increase of seizure number, there was a trend of gradual prolongation of the seizure duration. In FS + ZnPPIX group, the seizure latency was gradually shortened and the seizure duration was further prolonged. There were no significant differences in seizure intensity and rectal temperature between the two groups. After recurrent FS, by using light microscope we could see that the arrangement of hippocampal neurons was disordered, polarity was not clear and vacuolization appeared in some neurons. At the same time the ultrastructure of hippocampal neurons under electron microscope changed, which manifested as mitochondrial swelling, dissolved and ruptured ridge and vacuole formation, and dilated rough endoplasmic reticulum (RER). ZnPPIX aggravated neuronal injury. No obvious loss of hippocampal neurons was observed in FS group, while the number of hippocampal neurons in CA(1) and CA(3) subfields in FS + ZnPPIX group decreased respectively as compared with that in FS group and in control group (P < 0.01 for all).
Conclusion:
The study by using ZnPPIX which is an inhibitor of HO showed that endogenous HO/CO might act as a protective factor in FS-induced brain damage.
