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Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Functional response of hippocampal CA1 pyramidal cells to neonatal hypoxic-ischemic brain damage
Yan-Dong Zhao1, Sai-Yu Cheng, Shan Ou
1Department of Neurobiology, College of Basic Medical Sciences, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
Insights
Perinatal hypoxic-ischemic (H-I) brain injury in newborns causes immediate electrophysiological and synaptic changes in the hippocampus. Reduced glutamate transporter expression contributes to excitotoxicity in developing brains.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Perinatal hypoxic-ischemic (H-I) injury is a leading cause of neonatal brain damage.
- The hippocampus is particularly vulnerable to H-I injury, leading to neuronal loss.
- Neuronal functional changes may precede morphological alterations following H-I events.
Purpose of the Study:
- To investigate the immediate electrophysiological and synaptic transmission alterations in the neonatal rat hippocampus after H-I injury.
- To assess the role of glutamate transport in H-I-induced hippocampal damage.
Main Methods:
- Utilized Sprague-Dawley rat pups subjected to H-I or sham procedures.
- Employed patch clamp electrophysiology, immunohistochemistry, and Western blotting.
- Analyzed CA1 pyramidal cell excitability and synaptic currents.
Main Results:
- Observed decreased neuronal excitability and increased frequency/duration of spontaneous excitatory postsynaptic currents (EPSCs) in H-I rats.
- Found reduced glutamate transporter subtype 1 (GLT-1) expression in the hippocampus of H-I group.
- No significant changes in excitatory postsynaptic current amplitude or expression of AMPA, NMDA receptors, and synaptophysin.
Conclusions:
- Electrophysiological and synaptic function changes occur rapidly after neonatal H-I brain injury.
- Impaired glutamate clearance due to decreased GLT-1 expression is a key factor in hippocampal excitotoxicity.
- These findings highlight early functional deficits in H-I brain injury models.
Abstract:
Perinatal hypoxic-ischemic (H-I) is a major cause of brain injury in the newborn. The hippocampus is more sensitive to H-I injury than the other brain regions. It is believed that H-I brain damage causes a loss of neurons in the central nervous system. The patterns of neuronal death include apoptosis and necrosis. With regard to the responses of neurons, the neural functional changes should be earlier than the morphologic changes. The aim of the present study is to evaluate the electrophysiological characteristics and the synaptic transmission functions. Seven-day-old Sprague-Dawley rat pups were randomly divided into sham operation and H-I groups. The patch clamp, immunohistochemistry and Western blotting techniques were used to achieve this objective. The results of the study showed a decrease in neuronal excitability and a significant increase in the frequency of spontaneous excitatory postsynaptic currents and the duration of EPSCs in the CA1 pyramidal cells of H-I brain damage rats. The glutamate transporter subtype 1 (GLT-1) expression level of the hippocampal CA1 area in the H-I group was decreased compared with the control. There was no difference in the amplitude of excitatory postsynaptic currents and should be no difference in the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR), N-methyl-D-aspartate receptor (NMDAR) and synaptophysin between the control and H-I brain injury group. These results revealed that changes of electrophysiological characteristics and synaptic functions occur instantly after H-I brain damage in the hippocampal pyramidal cells of neonatal rats. The failure to eliminate glutamate should be one of the important factors of excitotoxicity injury on hippocampal CA1 pyramidal cells, while neuronal excitation was not increased in the H-I brain injury model.
